key: cord-0006862-qxy5kshs authors: nan title: European Association of Nuclear Medicine Congress: 20 – 24 August 1994, Düsseldorf, Germany date: 1994 journal: Eur J Nucl Med DOI: 10.1007/bf00177741 sha: 288e7977d05d8ed74d89292b2ec469d6fffacde4 doc_id: 6862 cord_uid: qxy5kshs nan Recently, we have demonstrated the feasibility of imaging myocardial uptake of F18-fluorodeoxyglucose (FDG) with SPECT. The aim of the present study was to determine whether FDG SPECT could predict reversibility of regional wall motion (RWM) abnormalities in patients undergoing revascularization. We studied 15 patients prior to revaseularization (9 CABG and 6 PTCA); all had RWM abnormalities as assessed with 2D echo. Each patient underwent resting thallium-201 SPECT (to evaluate regional perfusion), and a FDG SPECT during a hyperinsulinemie glucose clamp. After revascularization 2D echo was repeated to study change in RWMA (15 segment analysis). The segmental wall motion was analyzed using a 0-3 score index (0=normo, l=hypo, 2=akinesia and 3=dyskinesia). For comparison of SPECT imaging with 2D echo, the my'ocardium was divided in 5 corresponding segments (apex, anterior, lateral, inferior and septal). The SPECT images were analyzed using PET criteria for viable tissue (hypoperfusion with relatively enhanced FDG uptake) and necrotic tissue (both decreased perfusion and FDG uptake). We identified 13 viable and 18 necrotic segments. In 10 viable segments RVgM recovered, and in 16 necrotic segments no change in RWM abnormalities was seen. RWM score decreased in viable segments after revascularization from 2,8+1.7 to 1.2__+1.2 (p<0.005). In the necrotic segments the RWM score remained unchanged: 3.3_.+2.1 vs 3.3+1.8 (p=NS). The sensitivity of FDG SPECT imaging to detect improvement in RWM abnormalities was 83% and the specificity was 84%. These data suggest that FDG SPECT can identify viable myocardium. 200 patients (pts) underwent assessment of myocardial viability by combined nuclear imaging using resting SPECT with Tc-99m MIBI for evaluation of myocardial perfusion and metabolic imaging by PET and F-18 FDG. During a 17+7 month follow-up 1081200 pts (53%) underwent coronary revascularization either by PTCA (46 pts) or CABG (62 pts) while 90 pts were treated medically and 2 pts underwent cardiac transplantation. 72/108 pts had follow-up angiography 6-+1 months after revascularization (35 pts with 3-+1 CABG, 37 pts with single-vessel PTCA). Results of regional wall motion (RWM) comparison (RWMl=baseline, using the centerline method are expressed in SD of a normal population with negative values indicating hypokinesis. RWM comparison in regions with reduced peffusion (regional MIBI uptake below -2SD of a normal population) is given for three groups categorized by preoperative viability imaging: A: FDG >70% of normal perfused region (viable with "mismatch"), B: FDG 51-70% Cintermediate"), and C: FDG <50% ("scar"). PTCA CABG A -2.7+1.0 -1.6_+1.1 1.1_+1.0 -2.2+1.0 -0.6-+0.8 1.6+1.0" B -1.4-+0.9t -0.9+1.9t 0.5+l.lt -1.1-+0.8t -1.4-+0.7t -0.3+0.6t" C -2.2+-.0.7 -2.2+_0.5 0!-0.3t -2.4---t-0.7 -2.8-+0.6-? -0.4_+0.5-? * p< )5 vs PTCA, "~ p vs group A Following PTCA, EF improved from 49+11 to 52-+10% and after CABG from 43+11 to 50-&12% (p<0.05). Thus, functional outcome of RWM was similar following either PTCA or CABG for the tissue subgroups. However, recovery of RWM in "mismatch" regions and of global function was slightly better after CABG which might indicate more severe preoperative ischemia or the effect of complete revascularization in patients with multivessel disease. Maintained glucose metabolism assessed by FDG and PET indicates preserved viability of hypoperfused and dysfunctional myocardium. To evaluate the regional relationship between the severity of MIBI perfusion defects and FDG uptake, resting MIBI SPECT studies of 174 patients (85% male, 58_+9 years, 84% with previous myocardial infarction) were compared with data acquired by PET and FDG. MIBI and FDG uptake was evaluated by a computerized semiquantitative analysis for 13 left ventricular regions. The region of maximal MIBI uptake was set as 100% for both data sets and regional uptake of both tracers was normalized to this reference region. FDG uptake >70% was defined as lower threshold of preserved viability (v) and FDG uptake <50% was categorized as definite evidence for scar (s) tisssue. Results are given in the territories of the 3 coronary arteries and are divided in moderate (31-50% of individual maximum) and severe (-<30%) defects. i MIBI RCA defect nl,: l moderate 191 52 39 1 39** 27 severe 69 87 67 25* 38 v and s are % of n, * = p<0.0~' and ** = p< 0.01 vs LAD There were significantly more hypoperfused but viable regions in the LCx and RCA territories as compared to the LAD territory where the MIBI defect severity reflected more accurately myocardial viability as identified by FDG PET. Regression analysis in regions with reduced MIBI-uptake (<-2SD of a normal population) revealed a correlation between MIBI and FDG uptake with r--0.60 in the LAD, r=0.43 in the LCx, and r=0.35 in the RCA territory. These regional differences are probably due to soft tissue attenuation artifacts and have to be considered in the clinical evaluation of patients with coronary artery disease if the severity of MIBI defects is used as an indirect parameter of myocardial viability. Myocardial blood flow (MBF) estimates with PET and O-15 water or N-13 ammonia have been shown to distinguish viable from nonviable myocardium. To evaluate whether other model parameters, such as the recovery coefficient in the water model and K1/K2 from the ammonia model, may provide additional information, 14 coronary patients (pts) with anterior wall dysfunction underwent PET with O-15 water and N-13 ammonia before revaseularization. In addition to MBF, (x, the recovery coefficient from the 1-compartment water model, and K2, the backward transport rate constant from the 3-compartment ammonia model, were computed. Because overestimation of MBF has been noted in infarcted segments with 0-15 water and the standard 3-parameter model (WA 1) where recovery is a fitted parameter, MBF was also determined from a water model with a priori knowledge of finite resolution effects (WA 2). Five pts had viable myocardium, defined as improved regional anterior wall motion score by >1 full grade and reduced end-systolic volume at 2D-echo 2 months after revascularization, while the remaining 9 pts had nonviable myocardium Baseline PET parameters in the 2 groups are shown in Thus, viable myocardium is associated with higher MBF by ammonia or WA 2, higher K1/K2 and a larger recovery coefficient than nonviable myocardium. A. Mastorakou, C. Giannakenas, J. Tselfes, D, Apostolopoulos, T. Gorilas, N. Mastronikolis, M, Matsouka*, P.J. Vassilakos, Depts. of Nuclear Medicine and "Hematology, Regional University Hospital, University of Patras, Medical School, Patras, Greece. The object of this continuing study was to assess the sensitivity of 111-In labeled Octreotide (00 in the detection of malignant lymphomas and/or the extent of known disease, The results were compared to CT and/or MRI, U/S and 67-Ga citrate scintigraphy. Thirty seven patients, mean age 60y, (range 23-78] underwent planar scintigraphy, (9 also underwent SPECT), 6 and 24 hrs after the injection of 2,8-3,0 mCi of 111-1n-0C. 34 patients had histologically confirmed lymphomas (13 Hodgldn's disease and 21 NHL), while the remaining 3 patients were under investigation for suspected lymphema (confirmed histologically as Hodgkin's lymphoma in 2 and infectious mononucleosis in 1}. All patients had previous investigation with other modalities ( CT, u/s and/or MRI }. In 30 patients whole body 67-Ga-Citrate planar scans were performed at 24 and 48 hrs p,i. Superimposition imaging techniques were applied between SPECT transaxial slices and the corresponding CT sections. The OC-scan was true positive in 34 patients (91,9%), in 1 case it proved true negative (inf. mononucleosis), while it was false negative in 2 patients (5.4%), Concerning the extent of the disease, 109 different sites of 111-1n-0C accumulation were detected. In 7 patients OC led to re-staging of the disease, while in 12 patients OC confirmed the presence of the disease in suspected sites, in comparison to other modalities OC proved superior in detecting more lesions in 17 of the 34 positive cases (50%), similar in 12 patients (35,3%) and inferior in 5 (14,7%) cases. The 67-Ga-Citrate scans failed to detect the disease in 6 of 30 patients and proved inferior in defining the extent of the disease. Lesions in the upper abdominal region were more readily detected by SPECT in 9 cases, Superimposition techniques permitted the comparative imaging of the lesions. All the above mentioned findings were confirmed either by needle biopsy and/or by surge~. In conclusion it appears that OC is superior to the conventional modalities in lymphoma imaging often leading to the restaging of the patients. Also, with the implementation of superimposition techniques and SPECT the detection of the disease and its extent is much enhanced, This becomes even more evident in sites located within the abdominal region, The aim of this study was to investigate myocardial glucose metabolism and perfusion in the arrhythmogenie loci of patients with monofocal ventricular tachycardias (VT) . We studied I0 patients with VT. The arrhythmogenic foci were localized by end0cardial catheter mapping of the left ventrJcular wall (ECM). Myocardial glucose metab01ism was evaluated llsing the PET-camera PC-4096 and F-18-FDG after oral glucose load. Myocardial perfusion was determined with T1-or MIBI-SPECT, Per'fusion and glucose metabolism were analyzed in 19 myocardial regions using a fivepoint rating scale ranging from missing to maximal accumulation. A mismatch between myocardial glucose metabolism and perfusion was diagnosed when the FDG score was at least two points higher than the perfusion score. In 9 of 10 patients at least one area of mismatch between perfusion and glucose metabolism was found. The ECM localization of the VT loci was in 6 of these patients within zones of mismatch; in 2 patients the ,ECM localization of the VT focus was in the margin of such a zone; one patient had no coloeallzation of the arrhythmogenic focus and his zones of mismatch, The data suggest that most arrhythmogenic loci are localized in regions of hibernating ' myocardium, The n o ninvasive localization of zones of mismatch between perfusion and glucose metabolism m a y be of importance in planning revascularization or electrical ablation of foci in VT patients, The aim of our study was to assess the value of SRS in 21 patients (9 females and Ii males, age 24-86 years) suffering from m a l i g n a n t lymphomas. The h i g h -g r a d e NHL contained 12 true p o s i t i v e and 30 false negative loci, whereas in the HL group there were i0 true p o s i t i v e and 7 false n e g a t i v e lesions. The respective s e n s i t i v i t i e s were 37 %, 29 %, and 59 %. All the foci seen on SRS had been known before scintigraphy. In conclusion, SRS does not seem to improve the diagnostic m a n a g e m e n t of m a l i g n a n t lymphomas. This may be due to low receptor densities and/or to the presence of receptor subtypes for which l l l -I n -P e n t e t r e o t i d e has low affinities. One of the main problems in patients with lymphomas after first line treatment is the diagnosis of residual viable tumor tissue for further treatment planning. We used PET in patients with recurrent Hogkin's (HL) and Non-Hodgkin's (NHL) disease to quantify the tumor perfusion and metabolism prior and after second line chemotherapy. The primary aim of the study was the detection and quantification of residual tumor metabolism during restaging in order to optimize the further chemotherapeutic treatment protocol. Furthermore, followup studies with PET were used to evaluate the effect of the treatment protocol. SPECT with Tc-99m-Sestamibi was used for the evaluation of multi drug resistance (MDR). The PET results were compared to morphologlc (CT) and clinical data. The preliminary evaluation includes 32 (HL, 15 patients) and 33 (NHL, 17 patients) lesions. FDG (130-350 MBq) is injected for tumor metabolism studies, while O-15 labeled water {2088-2811 MBq) is administered to assess the tumor perfusion. SPECT studies were performed 30 min after intravenous injection of 370-555 MBq Tc-99m-Sestamibi for the evaluation of MDR. The quantitative evaluation of the iteratively reconstructed PET data was performed using a ROI-technique. SUV were calculated from the ROI data. The perfusion values ranged from 1.63 to 3.31 SUV in all lesions, while significantly lower values were calculated for the normal soft tissue (0.64 SUV, mean value). The metabolism was increased in the malignant lesions and with a large range between 1.42-and 13.35 SUV. The FDG uptake in normal soft tissue and scar tissue was 0.6647).90 SUV. No significant correlation was noted for tumor perfusion and metabolism. Furthermore, no significant differences were found for HL and NHL We were able to compare the FDG uptake prior and after one chemotherapeutic cylce (dexamethasone, BCNU, etoposide, alexane, melphalan for HL; alexane, mitoxantrone for NHL). While the tumor metabolism was significantly lower after therapy in 5 of 9 lesions, no change was noted in 3 tumors. A decrease in tumor metabolism and no change in morphology (CT) was noted in three lesions responding to therapy. The accumulation of Tc-99m-Sestamibi and the FDG metabolism prior and after therapy was compared in 10 patients. Again. the change in FDG metabolism correlated with the restaging data. The uptake of TC-99m-Sestamibi was predictive for MDR. Progression of disease was observed in four patients without Sestamibi accumulation, while response to chemotherapy or stab]e disease was associated with Sestamibi uptake (n=4). Our results show, that PET studies with FDG are a promising tool for both diagnostic evaluation during restaging and therapy planning in HL and NHL patients. The SPECT studies with Tc-99m-Sestamibi may help to detect MDR, when the size and location of the lesion permit a qualitative evaluation. Energy metabolism Of hematopoetic bone marrow (BM) is mainly based on glucose utilization. Aim of the present study was to evaluate FDG-PET for characterization of BM metabolism of cancer patients (n=26). Static PET was performed 46+18 minutes after i.v. injection of 224__+68 MBq FDG. Differential uptake ratios (DUR) for bone marrow of the thoracic or lumbar spine were determined using the ROI technique (21 + 12 ROI/scan; coronal and sagittal slices). BM diagnosis (normal, normal after chemotherapy [0-90 d], malignant infiltration, stimulation before planned autologues BM transplantation, irradiated BM) was established by histology, CT/MRI and/or clinical followup. Compared to normal (DUR: 1.93+0.43; n=13), increased FDGuptake was observed in patients with malignant BM infiltration (DUR: 3.41 +0.43; n=4) and-after external BM-stimulation (DUR: 3.86; n = 1), however, not during physiological BM-regeneration (DUR: 1.94+0.55; n=6). Radiotherapy caused a marked decrease of FDG-uptake (DUR: 1.19; n=2). We conclude that FDG-PET is suitable for characterizing hematopoetic bone marrow metabolism. It might be useful to improve noninvasive treatment control in patients with neoplastic bone marrow involvement. The diagnostic performance of IBZM-SPECT for discriminating idiopathic from other parkinsonian Syndromes is acceptable (sensitivity: 83%, specificity: 77%). Optimal thresholds varied in the different entities, Discrimination capacity Was evidently s u~o r for using S/FCratios compared to S/OC-ratiOs, thus supporting the FC as reference. De novo patients may be classified more accurately than those pretreated with doparninergic drugs prior to the SPECT study. PD is characterized ~y the degeneration of d o p~i n e r g l c neurons in the basal ganglia. In vivo v i s u a l i z a t i o n and m e a s u r e m e n t of the dopaminergic system in b r a i n structures of Parkinson patients ~s enabled by the SPECT t e c h n i q u e W i t h t h e 1 -1 2 3 l a b e l l e d p o s~s y n a p t i c dopamine D2 r e c e p t o r agonist Lisur~de. A i m of our study was no c o r r e l a t e SPECTfindings with clinical data of 17 untreated patients with idiopathic PD (age 48 -75, mean 59.6, SD 7.7)~ which showed response to dopaminer~ic treatment after the SPECT Study~ S P E C T scans were p e r f o r m e d 2 hrs a f t e r injection o~ a p p r o x i m a t e l y 185 M B q 1-123 Lisuride. Transverse slices Without attenuation correction were used to calculate ratios between the right and the left side o~ the basal ganglia (R/L) and between basal ganglia an~ frontal cortex (B/FC). Significant correlation between R/L and the ratio of the scores of the U P D R S -s c a l e for the right and left side is found (p=0.0181, r=0.5650).Additionally we observed a negative correlation between the age of the patients and B/FC (p=0.037, r=-0.4448). Our results suggest, that the Lisuride-SPECT visualizes dopaminergic degeneration in PD on the base of the q u a n t i t a t i v e c o r r e l a t i o n between R/L uptake ratio and severeness of disease. Previous studies have s h o~ that NCQ-298, a salicylamide ((S)-3iodo-N-[( 1 -ethyl-2-pyrr olinidyl)met hyl]-5,6-dimethox3'salicylamide labelled with 1-125 and 1-123, possesses the prerequisite pharmacological properties to be used in vivo for the visualisation of dopamine D2 receptors (-Hall et al, 1991, Psychopharmacology, 103:6-18). In SPECT studies in baboons, 1 h aRer injection of 1-123 NCQ-298 the radioactive concentration in the striatum reached a plateau that remained constant for 4 h. The striatum to cerebellum radioactivity concentration ratio values: S/C (uncorrected for partial volume effects) were 10 and 21 at 1 h and 4 h, respectively. In humans, brain SPECT studies were performed with a double head DST Sophy y-camera equipped with ultra high resolution parallel hole collimators, after i.v. administration of 150 MBq of 1-123 NCQ-298. Sequential acquisitions of 64 images in 128* 128 (pixel=3.4 mm) were obtained over 360 ° with the smallest circular orbit. Tomographio images were reconstructed by filtered hack projection with resolution recovery Butterworth apodisation. The observation of the radioactivity distribution in the brain showed an accumulation of the radioactivity in the basal ganglia as soon as 0.5 h after injection with a maximum at 3-4 h; on the contrary the radioactivity in the others structures cleared continuouly from an early maximum (10 rain). 6 h post injection, the S/C ratio value reached 40. These results suggest that I-123 NCQ-298 has the potentiai of being used tbr clinical SPECT investigations of cerebral D-2 receptors in the human brain. Serotonin (5HT) uptake inhibitors are substances which are widely used for the treatment of depression and other psychiatric syndromes such as obsessive compulsive disorders.It aiso has been hypothesized that changes of 5HT uptake sites (US) in the brain are involved in the pathogenesis of depression. Up till now it has not been possible to measure 5HT-US in the brain in humans in vivo. The cocaine anaiog 2-l~-carbomethoxy-3-8-(4-iodophenyl)-tropane (13-CIT) is a ligand for both DA-and 5HT-US which in its [I-123] labeled form can be used for SPECT.SPECT-experiments in primates have shown that I~-CIT binds to 5HT-US in the brain stem and to DA-US in the striatum. The purpose of the present study was to compare [123I]-1~-CIT binding in the brain stem (pens, midbrain and hypothaiamus) of normal controls and patients under treatment with citalopram. After informed consent 12 depressive patients under 20mg (n=6) or 40mg (n=6) Citaiopram daily and 10 normal Controls were studied 2, 4. 16, 20 and 24 hours after i.v. injection of 111 to 148 MBq using a triple head gamma camera (Siemens Multispect). After reconstruction and attenuation correction ROIs were drawn in axial slices in the brain stem, stdatum and cerebellum using a brain atlas.Cpm's per pixel were caiculated, decay corrected to the time of injection, and corrected for body weight and injected dose. Specific binding was defined as target minus cerebellum. Results show a highly significant reduction of 13-CIT binding in the brain stem in patients under citalopram compared to controls (41 + 13 vs 83 _+ 48 cpm's, 4 hrs pSnj., p < 0.0001) which was dosedependent. No changes were found in the striatum. To our knowledge this is the first report directly demonstrating the effect of a selective 5HT uptake inhibitor in the brain in humans in vivo. SPECT measurements of 5HT uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action. The function of extrastriatal brain regions may play an important role in diseases such as schizophrenia. PET and SPECT has hitherto been used for the determination of dopamine receptors in the major basal ganglia. In extrastriatal regions the potential for examination of dopamine receptors is limited by the low receptor densities, which are 10-100 times lower than in the basal ganglia. For previously used radioligands the affinity is too low to visualize these receptors. Suitable radioligands for extrastriatal dopamine receptors should be selective and have a very high affinity to provide high specific binding at low free radioligand concentration in brain. The radioligands examined were [C-11] FLB 457, which is a selective benzamide with a very high affinity (Kd) of 20 pM for dopamine D2 receptors in vitro, and another potent dopamine D2 receptor ligand [I-125] epidepride which is structurally closely related to FLB 457 but contains an iodine. Both were prepared with a specific radioactivity >1500 Ci/mmol. In PET examinations on healthy human subjects [C-11]FLB 457 accumulated not only in the basal ganglia but also in several extrasn'iatal regions. Uptake in the thalamus, amygdala, substantia nigra, colliculus and neocortex was 2-5 times higher than in the cerebellum. In extrastriatal brain regions radioactivity reached a plateau at about 50 nfinutes after injection. Assuming that radioactivity in the cerebellum reflects the level of free and non-specific binding, the specific binding in extrastriatal regions was on a maximal level within 60 minutes. Human post-mortem whole hemisphere autoradiography using [I-125] epidepride demonstrated labelled receptors in nucleus candatus, putamen and pallidum and also in extrastriatal areas such as thalamus and the substantia nigra. Specific [C-11] FLB 457 binding should be appropriate for a quantitative equilibrium analysis of extrastriatal dopamine receptor densities with PET. With highresolution SPECT cameras it should be possible to visualize extrastriatal dopamine D2 receptors using [I-123]epidepride. We have d e v e l o p e d SSTR-binding peptides (>50) which can be l a b e l e d with Tc-99m to very high specific activity (300 Ci/mMol). The tumor uptake-kinetics of these Tcpeptides were compared with In-Oct in rats bearing Longnecker tumors (pancreatic tumor line CA20948). Each of the peptides was prepared to contain a N~S or N~S~ chelator, labeled with Tc-99m by liga~d exchange, purified by HPLC and assayed in vitro for SSTR bindinu affinity. Rats were in3ected~-~-~--~.v, with 0.2mC{ o f Tc-peptide (16~g/Kg) or 10-50~Ci of In-Oct(2.0~g/Kg). To assess in vivo tumor specificity of Tc-peptides, selected rats were preinjected s.c. with a receptor blocking dose of Oct(4mg/Kg). The tumor uptake-kinetics were studied by g a m m a c a m e r a imaging and %ID/g of the tumor was determined at 30, 60 and 90 min following sacrifice. The mean %ID/g (n=5) and Tumor~muscle (T/M) ratio for selected peptides are as follows: The rise kinetic of serum CA 125 level prior to diagnosis of clinically evident relapse showed agressivity of the recurrence. The aim of this work was to evaluate the prediction value of the doubling time (T1/2) calculated according the formula : T1/2 = (log2 * t) / log[(CA 125)2/(CA 125)1] in which t is the interval in days between the final and the initial measurement. CA 125 levels were first estimated with ELSA CA 125 and then with EIA CA 125 (CIS Bio International). The doubling time of CA 125 was calculated in 42 patients with epithelial ovarian carcinoma : 55% of half-lives were inferior to 60 days. They were inversely correlated with initial serum half-lives of CA 125 measured during the first cycles of chemotherapy (p<10-6). The more acute rises of serum antigen level were observed in sera of patients who did not responded quickly to firstline chemotherapy. The relative risk of relapse and death in patients with doubling time of less than 60 days were respectively 4,3 (p<10 -4) and 5,3 times (10 -4) higher than in patients in patients with doubling time of 60 days or more. The median time of relapse free was 21 months for patients with doubling time of 60 days or more and 11 months for the others patients. The median time of overall survival was 36 and 16 months for each category respectively. In conclusion, the measurement of the serum CA 125 doubling time prior to clinically evident relapse allowed the prediction of the prognostic of the recurrence and the adaptation of a appropriate therapeutic. The breast,lung and prostate cancer ,are considered to give frequently bone metasteses. Tumor markers (T.M~ are usefull in the follow-up of these diseases and in early diagnosis of the relapse. The aim of this study,was to correlate bone sean(B.S~ and sensitive(T.M]in each case,to find out the (T.M)that we can use as the most sensitive or what is the combination for best results and finally to determine what is the role of positive (T.M) in negative (B.S). We examined 158 pts,62 with breast cancer,30 with lung cancer and 64 with prostate cancer. We measured serum levels of CEA,Ca-125,Ca 15-3,TPA,PSA,b'microglobulin,ferritin,and alkaline phosphatase. 58 pts had positive(B.S). The best sensitivity of (T.M) in breast cancer was 88,2~ forCa 15-3,86,6~ for CEA and 76,4~ for TPA. In lung cancer was 88,8~ for Ca-125 and 87,5~ for TPA and in prostate cancer 70,8~ for PSA and 70,4~ for b'mieroglobulin. Of the 100 pts with negative (B.S) 31 had I(T.M) elevQted,9 had 2(T.M)above the normal values and only 7 pts had 3(T.M) elevated(3 with liver metastasis 3 with lung metastasis and I with brain metastasis). Conclusion. In the follow up of pts with malignant diseases,when we search for bone metastases,its usefull to eombine(B.S) and(T.M) as Ca 15-3 and TPA in breast cancer, Ca-125 and TPA in lung cancer and PS& and alkaline phosphatase in prostate cancer. When the(B.S)is negative and(T.M)levels are above normal limits (in three of them at least),we must search for other metastases as hepafique,lung or brain. The injection of murine m0noclonal antibodies for immunoscintigraphy of ovarian cancer patients induces human anti-mouse antibodies (HAMA). Longer survival rates have been reported in patients developing high and persisting HAMA titers. This has been related to the enhancement ot the anti-tumor response induced oy antiidiotypic antibodies. We tiave studied the phenotypes and the cytotoxic activity of peripheral blood lymphocytes ~BL) in patients Before and during the development of tTAMA comparing the immunological parameters and the chnical course. For phenotyping of lympYao.cytes, intertering HAMA were eliminated By Ficoll gradient centrifugation and the following antigens were determined 15y flow cytometr7: CD4, CD8, CD3, CD19, CD56, CD2, CD25, CD45and HLA-DR. For measuripg the cytotoxic activity, NK-cell and non-MHC restricted T-cell activity was aetermined with a fluorescence-based assay. In addition the IL-2 sera levels of the patients were regularly determined. Until now, PBL of 40 patients injected 1 to 7 times with 1 to 2 mg intact MAb Tc-99m B43.13 ~Biomlra, Canada) have undergone phenoty.ping and functional analysis at intervals of 4 to 8 weel~s over a perio~l of 3 to 20 months. In comparison, the PBL of 10 healthy controls, not previously expose~t to murine immunoglobulins, served as controls. The results demonstrate that high HAlrCIA titers [103-5x105 ng/ml) are often associated with remarkable cytotoxic activity and phenotypes ot peripheral blood lymphocytes which remain on a persistmg level with usually high values. Whereas HAMA-titers below 1000 ng/ml are often accompanied by_ PBL with low cytotoxic activity sometimes decreased to 20% ot" the normal values, which also 'show great immunological instability. F urt. h ermor % it was p.ossible to define immunological parameters which correlate with the progression ot tumor growth. Concerning the functionality of non-lVlHC restricted cytotoxlc T-lymphocytes we noticed an increase of more than 100% indicating a decrease ,n specificity concerning T-cellular activity. These immunologial parameters obtained by long-term functional analy.sis, phenotyping of peripheral lymphocytes and serum [nterleukin-2 determination are useful m accompanying future immunotherapy of cancer patients. The image quality of lung ventilation studies carried out using Technegas was compared to that obtained with Tc-99m DTPA aerosol. The effect of choice of tracer on the final ventilation-perfusion (VP) scan report was also assessed. A total of 192 VP scans from four groupsof patients were used in the assessment. Groups 1 and 3 were ventilated using Tc-99m Technegas, groups 2 and 4 were ventilated using Tc-99m DTPA aerosol. For each scan the age of the patient, the presence or absence of aerosol clumping, the number of ventilation defects (no defects, one or two defects or > 2 defects) and the final clinical report (obtained using the Biello criteria) was noted. No significant differences were found between groups 1 and 3 or groups 2 and 4 therefore these results were pooled to give two groups of 96 patients, one for Teehnegas and one for DTPA aerosol. All comparisons of the two ventilation agents were performed using the Pearson chi-squared test. The mean age of the patients was 56 years and there was no significant difference in the distribution of ages in the two groups (p>0.05). There was a significant difference (p<0.001) in the number of scans with aerosol clumping present, with 19% of the Technegas scans compared to 41% of the DTPA scans showing this feature. Multiple ventilation defects were present in 23% of the Technegas scans and 35% of the DTPA scans but the differences were not significant (p=0.054). Despite the differences in image quality, the choice of ventilation agent had no significant effect on the final report (p>0.05). SCINTIGRAPHY OF SMALL CELL LUNG CANCER (SCLC) USING 111-In DTPA-OCTREOTIDE In vivo visualization of SS receptors has recently been described using the somatostatin analogue l llIn-Labelled octreotide. Twenty-one patients with histologically proven SCLC were examined : 17 at tumor presentation, 4 had previous therapy.Patients were staged on the basis of chest X-ray, serum neuroenolase (NSE) determination, fiberoptic bronchoscopy, bone scintigraphy, abdominal US, chest and brain CT scan. In few patients planar scintigraphy was performed, 1,5, and 24 hours after i v injection of 110 MBq of 11 lIn-Octreoscan.The 11 lIn-Octreotide tumor uptake registered at 5 hours from the injection was good and the imaging was comparable to that of late scan; for this reason the standard examination was manteined at 5 hours. Scanning was done with a Toshiba GCA 901/A gamma camera equipped with a medium energy collimator. SPECT of the thorax and of particular regions of interest was performed. In 20 out of 21 patients lung tumors were visualized at 5 hours scan. The negative case had undergone to a previous chemotherapy. The last scan, when performed, confirmed in all patients the positivity or the negativity of the imaging obtained with the early scan. Octreotide uptake was in generally more extensive than expected from RX and CT studies. The somatostatine analogue visualized all the lesions were demostrated by means of other instrumental examination with the exception of 2 liver metastatic sites, 2 lymph-nodal metastases, 1 adrenal metastases detected by US and/or CT scans; on the contrary l llIn-Octreotide scintigraphy revealed 5 unknown distant lesions (3 lymph-nodes, 1 bone, 1 brain) previously not identified with standard examinations. Octreoscan was effective in imaging tumor sites also in patients with low NSE values. The purpose of this study was to assess the diagnostic accuracy of preoperative PET in hyper parathyroidism (HPT). Ma~erial: Before operation (n=10) or reoperation (n=ll) 21 patients with HPT were examined by PET following intravenous (i.v.) inSection of 400-~ 800.MBq of L-methyl-~C-methionine. In 6 patients PET was repeated during or in~ediately after i.v. infusion of Na2-EDTA. A General Electric whole body 4096 PET c~mera was used. After a i0 min transmission scan a dynamic sequence was performed and an average image (14-45 min) produced and recalculated to provide images of standardized uptake values (SUV). Regions of interest were drawn by a standardized procedure. Contrast enhanced computed tomography (CT) was carried out in 17 patients on a Siemens Somatom Plus CT-scanner using 4 mm contiguous slices. In 18 patients ultra sonography (US) was performed (Acuson 128, 5 9~z). Results; Sugery revealed enlarged parathyroid tissue in 20 patients but not in 1 patient. PET was true positive in 76%, false positive in 19% and true negative in 5% of the patients. CT was true positive in 65% and US in 50%. The results suggest tht PET may provide novel possibilities for preoperative parathyroid imaging in HPT. In this study, an attempt was made to administer Xe-t33 by ventilation into the tympanic cavity in order to quantitate uptake and clearance of the tracer as a measure of Eustachian tube function. 50 MBq of Xenon-133 gas filled in a 50 rrd syringe were administered to 15 ENT patients testing 3 different approaches. In 2 patients the gas was injected directly into the tympanic cavity via an in-place Armstrong tube. In another 5 patients Xe-133 was insuffiated into the epipharynx using a nasopharyngeal catheter. Subsequently the patients ~vere asked to perform Valsalva manoeuvres three times to imitate physiological ventilation of the middle ear. In a third group of 8 patients Xe-133 was administered via a nose olive while having Vatsalva manoeuvres done simultaneously, Immediately after gas application sequential gamma camera imaging for 30 rain and semiquantitative evaluation by ROI-techniques were performed. As a main result of this study it is to state that all three approaches were successful in trapping Xe-t33 within the middle ear space without major problems. Initial accumulation of Xe-133 in the tympanic cavity during the first two minutes yielded a right to left ratio of 51.1 +_ 10,2 % to 48.9 _+ 10.2 % in 10 patients with normal Eustachian tube function. The clearance half life ranged from 11.5 rain to 217.9 rain with a median of 96.2 min. One-sided malfunction of the Eustachian tube proven by impedance mesurements or even the beneficial effects of one-sided application of decongestive drugs could nicely be quanfitated both by initial trapping as well as by clearance half life, respectively. In conclusion, tympanon Xe-133 ventilation scintigraphy is an easyto-perform and low-radiation-exposure test for evaluating the middle ear ventilation and, thus, Eustachian tube function. Normal ranges are provided by this study, yet the clinical impact needs to be documented by especially designed ENT trials. Recent papers have demonstrated the usefullness of Tc MIBI scintigraphy (MS) and its potential superiority over thallium-201 for the diagnosis of parathyroid (PT) enlargement. In order to determine where would be the place of this new imaging procedure in the decision tree before surgery, we performed MS in I00 patients (pts) with suspected hyp. erparathyroidism (HPT). All I00 pts had both echographic and scintigraphic examinations. MS was performed using a double phase method, i.e. imaging time post injection was 15 mn and then 75 ran. Up to now, only 58 of these I00 pts, had unde~one surgical exploration. Based on the histologic control of these cases, we have established three major indications of MS in identifying PT adenomas. MS is superior to all other techniques for the diagnosis and localization of ectopic glands (6 pts in our group). MS is determinant in all cases of recurrent or persistent HPT. When concordance is found between echography and MS on a single site, local instead of general anaesthesia c~tn be proposed. The recent increasing demand for HPT exploration, coupled with the cardiac use of MIBI, allowed a dramatic reduction of the cost per patient, falling below that of thallium. We conclude that MS is a powerful tool for the strategy of localizing PT adenomas, especially when ectopic situation is suspected, and should be therefore performed in all patients with clinical and biological hype rparathyro ~' dism. compared to normal thyroid tissue. All 30 patients underwent surgery and histological examination after scintigraphy. MIBI scans were true positive in 16 of 30 patients, with 12 patients being positive in both planar and SPECT scans, 4 patients positive in SPECT images only. In 6 of the 30 patients, 1VRBI-scintigraphy was false negative. In the remaining 8 patients MIBI-scintigraphy was unable to detect any pathological finding, so did surgery too. False positive scans did not occur. In eond,alon, Tc-99m MIBI scintigraphy seems to be well qualified for the detection and localisation of parathyroid adenomas, especially if SPECT with modem triple-head cameras is used. Sensitivity, image quality and low costs enable Tc-99m MIBI to replace the often used TI-201 / Tc-99m subtraction Scintigraphy in most diagnostic situations. The purpose of this study is to cu.pm~ the d~tic value of SESTAMIBI LATE imaging, as proposed by Taillefer and SESTAMIBI-~ imaging techniques, in the preoperative localization of parathyroid lesions. Twenty eight patients were exEm/ned. SESTAkMIBI images were recorded with a pinhole collimator just after and two hours after injection of 300 MBq of 99r~c ~.~"IAMIBI . ~he thyroid image was obtained after injection of 300 MBq of 99m~c I~Kq[~C}~I~. The subtracT/on w~s performed with an already validated software. Late and subtraction images were interpreted blindly by three observers in each of the four q~rants of the thyroid field.Then 112 quadrants were analysed. Ectopic lesions %~are not taken into account in this study. Thirty one lesions (24 adencmas and 7 hyperplasias) were found at surgery. The sensitivities and specificities obtained are : We present the results of a retrospective study of 89 patients (mean age 58.4y;34M, 55F) with hyperparathyroidism (67 1,22 II or III) having undergone a PT scintigraphy (86 TI201 with Tc99m substraction, 3 MIBI) before surgery. 12 patients had been previously submitted to PT surgery. 1 scintigraphy was unreadable. There were 44 patients with adenoma, 31 with hyperplasia. In I0 patients, diagnosis adenomahyperplasia was uncertain; 4 were negative. The scintigraphic localisation of abnormal PT was complete (+) in 64/88 (72.7%), partial (+/-) in 9/88 (10.2%) and incorrect (-) Diagnosis of SWS may be difficult during the first year of life because neurological signs can be absent and radiological investigations can be normal. In order to test diagnostic value of SPECT at this age, regional cerebral blood flow was measured using Tomomatic 564 and !33-Xenon in 8 children with confirmed SWS, aged ! to 17 months, and in 16 controls of the same age. Three c h i l d r e n with SWS never experienced seizures before SPECT ; they showed hyperperfusion in the damaged hemisphere(+10 %) and p a r t i c u l a r y in the cortex u n d e r l y i n g m e n i n g e a l a n g i o m a (+ 20 %). C o m p a r e d to controls, interhemispheric and local asymetries were not significant (0.0575%), 180 segreents showed moderate reduction (51-74%) and 188 severe reduction ~50%) of tracer uptake. Of these 188 segments with severe reduction of resting MIBI uptake, 47 (25%) showed increased M1BI uptake (~.I0% vs resting study) after nitroglycerine administration (from 43+7% to 60i-8%, p<0.001). All these 47 segments were identified as viable on RR thallium (2 normals, 26 reversible defects, and 19 mild-moderate irreversible defects). Of the 141 (75%) segments with severe reduction of resting MIBI uptake and no change after nitroglycerine administration, the reajority (i00 segments) were identified as nonviable on RR thallium (severe irreversible defects); however, the remaining 41 segments showed evidence of viable myocardium on RR thallium (18 reversible defects and 23 mildmoderate irreversible defects). In conclusion, nitrate administration improves the differentiation between severely ischemic but still viable myocardiure from irreversibly fibrotic tissue using MIBI cardiac toreography in patients with chronic ischemic LV dysfunction. Beta-methyl iodophenyl pentadecanoic acid (BMIPP) allows for myocardial metabolic studies with SPECT. BMIPP uptake reflects the activity of acyl-CoA synthetase, a common enzyme in triglyceride synthesis and beta-oxydation. More reduced BMIPP uptake than flow tracer uptake (mismatching) may be observed in postischemic dysfunctioning myocardium early after acute myocardial infarction (AM/). To determine if mismatching is an indicator of viability, rest BMIPP (148 MBq) and rest MIBI (740 MBq) royocardial SPECT studies were obtained in 18 patients with left ventricular dysfunction 7_+3 days after AMI.. The relative uptake of the 2 tracers was compared (9 segs/P0 to the inotropic reserve assessed by 2D echo and low-dose dobutamine stimulation (5-10 mcg/kg.min). Long term functional recovery was assessed in all patients by 2D-echo after a 6 months follow-up. Of the 54 segs with dysfunction, 34 showed mismatching (12 pts) and 20 demonstrated inotropic reserve (7 pts). Of the 29 segs (9 pts) with improved walt motion at 6 months, 27 segs (9pts) showed mismatching and 16 segs (6 pts) demonstrated inotropic reserve (p< 0.01). The predicitve ~,alue (PV) of a positive or a negative test and their percent accuracy (Acc) to predict functional recovery were: SPECT mismatehlng ECHO dobutamine PV + P V -Ace PV + PV. We conclude that mismatched BMIPP and MIBI uptake in dysfunctional segments following AMI, is indicative of residual viable myocardium, whereas matched defects represent scar tissue. SPECT is at least equivalent to ECHO in the prediction of functional recovery. A. Bockisch, K.J. Hendchs, U. Wenderoth, J. Andreas, J. Meyer, H. Oehlert, K. Hahn. Klinik fiir Nuklearmedizin, E[. Medizinische K!inik, HTG-Chirargie; L Gutenberg-Universi~t, D-55101 Mainz, Germany , In our prospective study, 3 protocols of myocardial scintigraphy were performed in the same patients (pts) suffering from high grade coronary artery sten0sis. The results were compared with first pass radionuclid ventdculography (FP-RNV), coronarangiography (CA) and in each case with post surgical outcome. Scintigraphy was performed both prior to and 3 to 6 months after bypass surgery. The scintigraphic investigation included always FP-RNV at rest and under stress, and myocardial SPECT using 99Tc~-MIBI in a 2-days-protocoI, ~°~T1chloride standard protocol with 3 hours redistribution images, and in addition a rest reinjection (reinj.) 2 days after exercise. Up till now 43 pts have entered the study, which is completed for 20 of them. Compared to CA, the 3 myocard, scinti~ methods were found to have a very high sensitivity and specificity (98% of pathological areas) in the detection of coronary heart disease. However, concerning viability, the results differ considerably. Viability was missed in 61% of the akinetic areas diagnosed as scars by 2°1T1 standard protocol but only in 45% by 2°~TI reinj, and 49% by MIBI 2-days protocol. In our highly selected patient population, therefore, the use of a reinj, technique (MIBI and T1C1) is mandatory. Fatty acid metabolism is altered in ischemic or necrotic myocardium as PET-investigations have shown. To evaluate myocardial metabolism with SPECT radioionated fatty acids have been developed, however without clinical acceptance so far. In contrast to other radiolabeled fatty acids (e.g. 123I-IPPA) 123I-PHIPA 3-10, a phenylene bridged long chain fatty acid, is accumulated in the myocardium with a long biological half life of more than 15 h, indicating a "metabolic trapping". In order to evaluate the clinical relevance of 1231-PHIlaA 3-10 myocardial viability has been assessed in 9 patients with severe coronary heart disease. SPECT investigation using t23I-PHIPA 3-10 were compared with 20iT1 (stress / redistribution) and 99mTc-Sestamibi studies. In 8 patients myocardial scares were overestimated by 201Tl-redistfibution. In 13 regions with persistent 201Tl-d~2f~cts hibemating/s99tg~mwed myocardium could be identified as well with I-PHIPA as with Tc-Sestamibi. In 4 lesions no loerfusion with 99mTc-Sestamibi was observed, but a significant uptake of I23i.li.PHiPA implicated residual viable myoeardium. This could be confirmed by follow-up studies after revascularization where the perfusion with 99mTc-Sestamibi was improved. During a heart transplantation a double nuclide study using 131I-PHIPA and 99mTc-Sestamibi was performed. Scintigraphies of the explanted heart were compared to the preoperative scans, the activity of tissue samples and the corresponding histology. 131I-PHIPA and 99mTe-Sestamibi were accumulated in hibernating or stunned myocardium in a ratio of 2 : 1 according to their percent I.D. In scares however, the accumulation ratio of PHIPA / Sestamibi reversed to 1 : 2. These results imply that residual viable myocardium can be more accurately differentiated from scares with PHIPA 3-10 than with Sestamibi. Furthermore the different biodistribution of PHIPA and Sestamibi in hibernating myocardium and scares indicates that not only the perfusion, but the metabolic state of the myocardium can be evaluated with PHIPA 3-10. As a metabolic marker of the heart PHIPA 3-10 has the potential to improve the assessment of myocardial viability with SPECT. To assess whether rest Tc-99m Sestamibi (Mibi) could identify viable myocardium, we studied 15 patients with severe chronic coronary artery disease (three-vessel disease in 9 and two-vessel disease in 6) and left ventrlcular dysfunction (ejection fraction: 30-J:11%), referred to positron emission tomography (PET) for identification of viable myocardium. A combined study of perfusion ( potassium-38 or N-13 ammonia) and glucose utilization (18-FDG) was performed under hyperunsulinemic euglycemic glucose clamp. For each study, potassium-38 or N-13 ammonia and 18-FDG activities were determined in 19 myocardial segments. The segment with the highest potassium-38 or N-13 ammonia uptake was set as 100% for both data sets and segment uptake was normalized to this reference segment, Based on results obtained in control subjects, the thresholds for segment viability were defined as perfusion tracer uptake <70% and FDG uptake >70% of the reference segment. For each patient, Mibi activity (expressed as percent of peak activity) was determined in the19 segments by circumferential profile analysis. Comparison between PET and Mibi data was realized in a total number of 212 segments. According to PET criteria, 43 segments (20%) were non viable and 61 segments (29%) were viable. Mibi uptake was 50+17% and 59~-_17% in non viable and viable segments, respectively (p=0.01). Viable segments by PET 11 8 11 31 Noq viable segments by PET 13 12 5 t 3 The positive and negative predictive values for segment viability using a threshold of 60% of peak activity of Mibi uptake were 70% and 50%, respectively. Conclusion: On the basis of direct comparison with perfusion-FDG PET, Mibi uptake at rest is a poor iodioator of myocardial viability in patients with severe coronary artery disease and left ventriculer dysfunction. F-18-fluorodeoxyglucose (FDG) is widely used to study tumour metabolism by means of positron emission tomography (PET). The purpose of this study: was to determine the effect of insulin on the uptake of FDG in cultures of breast cancer cells in comparison to T1-201. Measurements of both tracers were performed in 160 cell culture tubes with incubation intervalls ranging from 1 to 240 min, Cellular FDG-and T1-201 accumulation was measured in a gamma counter and normalized to the activity added to the medium and to one million ceils expressed as %, with an average of 8.5 + 0. million ceils / culture tube: As shown in fig. 1 , linear accumulation of FDG over time was seen. A further significant increase from 3.52 _+ 0.74 % to 5 . 1 0 + 0 : 3 2 % at240min was attained after adding insulin; In i contrast, cellular uptake of TI' 201 did not differ Significantly with and without insulin, Extrapolating these results to FDG-PET tumor imaging a markedly improved tumor targeting might be obtained With simply replacing the common FDG injection by a continuous !infusion together with insulin. An optimum imaging period at 150 min after starting infusion incubationtim¢ [mini, lean be derived from our data considering the decay of F~18 as shown in fig. 2~ The potential improvement of PET image quality in tumor visualization with FDG by the approach suggested ought to be tested clinically. The aim of the study was the evaluation of FDG and thymidine uptake with time in zumor cell spheroids following irradiation in relationship to cell viability and proliferative capacity. Spheroids of a human adenocarcinoma cell line (SW 707) were incubated in media containlng C-14-FDG or H-3-thymidine (37 kBq/ml) for lh at 1,4,8,24 and 48h after irradiation with 6 Gy. Tracer uptake was measured per spheroid. The number of viable cells was determined using the mitochondrial enzyme activity (MTT-test) and the proliferative capacity of dispersed spheroid cells by the clonogenic survival assay. The uptake changed in the following manner (uptake of control = 100%),%__ The proliferative capacity decreased to 4% of control az lh recoverlng to 21% at 48h. The results indicate, that tracer uptake is changing with time and is higher for the viable cells than for the whole spheroid. The difference is depending on the number of survivlng cells. The high uptake at 8h is an indication for the recovery of the proliferative capacity. Adult T cell leukemia (ATL) is caused by human T cell leukemia virus type I (HTLV-I). This disease can be modeled in severe combined immunodeficiency (SCID) mice inoculated with the HTLV-t-infected leukemic cell line 43T. The purpose of this study was to examine the early and late distributions of these cells in vivo using In-111-oxine labeled 43T cells and radiolabeled anti-Tac (IL-2 receptor c, chain) monoclonal antibody (MAb), respectively, Early phase distribution was examined 2 and 6 days after the i.p. injection of 108 In-111-oxine-43T cells into SCID and normal mice. By day 6 significant accumulations of radioactivity were found in the spleen and thymus of SCID mice (33.3_+9.4 and 10.0~-_3.6 %lDtg, respectively) in comparison with normal mice (19.1.+.2.5 and 3.7_+0.9 %lDtg). The accumulations in other organs of SCID mice were not significantly higher than in those of normal mice. Late phase distribution was monitored in 43T-inoculated-SCID mice starting 28 days after i.p. injection of the cells (not labeled with In-111-oxine) by localization with I-t25 and In-111 labeled anti-Tac MAb (IgG2a) and an isotypematched control MAb. The 6iodistributions were examined 1, 2 and 4 days after i.v. injection of MAb. Significant amouts of In-111-anti-Tac MAb were found in the spleen and thymus of SCID mice (22~5±6.9 and 22.8_+6.9 %lDtg, respectively at day 2), whitzh were higher than those in the same organs of mice given In-Ill-control MAb (12.0±5.1 and 7.5=b4.6 %lD/g). Similar results were obtained with 1-125 labeled anti-Tac and control MAbs. These results were coincident with the histologicallyconfirmed infiltration of 43T in SCID mice, suggesting that the radiometdc techniques in this study could be used to evaluate the proliferation sites of 43T cells. Short acting benzodiazepine derivates have found wide clinical use in anesthesia. From previous studies we know t h a t in vivo the cerebral uptake of flumazenil (FMZ), a benzodiazepine receptor (BZR) antagonist, is considerably increased in rats anaestetized with isoflurane. However neither the benzodiazepine receptor density (Bmax) nor the affinity (Kd) is affected by isoflurane in vitro. In an attempt to explain these observations we i n v e s t i g a t e d the interference of isoflurane on the BZR in living baboons. An in vivo modeling analysis for [llC]FMZ kinetics was used which provides an estimation of the apparent Bmax (B'max) and the equilibrium dissociation rate constant KdVR (VR = volume of reaction). Results show that the apparent Bmax and KdVR of FMZ are significantly increased by about 100 % in a n i m a l s anaesthetized with isoflurane/nitrous oxide (1%/70%) in oxygen compared to animals treated with nitrous oxide alone. We suggest t h a t B'max e n h a n c e m e n t is due to isoflurane nonspecific interaction with the lipid bilayer structm'e, altering the membrane fluidity which might result in a facilitated receptor accessiblity for FI~LZ. This increased volume of reaction may also explain the increase of KdVR in our study. These results suggest t h a t the a n a e s t h e t i c effect of inhalational anaesthetics and BZR agonists in combination results not only from an additive but from a synergistic interaction by increasing the available binding sites for benzodiazepine derivates. Acridones show biological effects on various turnouts, possibly mediated by turnout cell uptake. The aim of this study was to label selected acridone derivatives and to determine the cellular uptake in comparison to T1-201 as a known non-specific tumour tracer. Acridone (AC) and 10-methyl-acridone (MAC) were radioiodinated with 1-123 by the Iodogen method. The monoiodinated products were separated by HPLC. The accumulation was determined in breast cancer cell cultures (n = 300) with incubation times ranging from 1 to 240 minutes. The uptake was calculated as the percentage (mean + 1 cr) of the added activity and standardized to one million tmnour cells. uptake during different incubation times in breast cancer cells The uptake of 2-iodoacridone (I-123-AC) was similar to TI-201. The higher lipophilic, methylated analogon (I-t23-MAC) showed an uptake twice as high. In conclusion, 1-123-MAC seems to have potential for turnout imaging. Further research is needed in other types of cancer cells as well as in-vivo studies with lipophilic N-substituted analogons. . PD can be associated with AF. Standard physiological and pharmacological tests do not allow to distinguish pre-and postganglionic neurons. So far the pattern of affection of the autonomic system in PD + AF has remained unclear. 5 patients with PD and AF were investigated with standard autonomic testing, magnetic resonance imaging (MRI) and J-123-MIBG-Scintigraphy. No patient was on any medication interfering with MIBG-Uptake during the study. Planar whole-body and anterior images of the chest were acquired 1 and 4 h following injection of 260 MBq J-123 MIBG. SPECT images of the heart were recorded after 4,5 h. 2 days later a myocardial perfusion SPECT at rest, lh after injection of 370 MBq 99m-Te-MIBI was obtained. MIBG imaging was also performed in 8 normal subjects, that served as controls. In all five patients no myocardial MIBG-Uptake was seen, neither planar nor by SPECT, Heart/Mediastinum ratios in patients and controls were 1,04 + 0.07 and 1,98 + 0.24 respectively (p< 0,0001). Myocardial perfusion imaging revealed normal findings in all patients. These results show that in pts with PD and AF postganglionic sympathetic efferents are severely affected. MIBG-imaging may be helpful for early diagnosis of AF in PD-pts by discriminating postganglionic damage from central nervous diseases with preganglionic affection of sympathetic neurons. Gamma-VinyI-GABA (GVG/Vigabatrin) is used as an add-on drug in patients with partial epilepsy. It protects GABA from elimination by irreversibly inhibiting GABA transaminase. GVG might also have a benzodiazepine effect on GABA receptors (GABA~), due to the functional coupling of GABA, and BZ receptors, and so effecting tZ~l-lomazenil SPECT scans. We speculated on a possible inhibitory effect of GVG on the binding of 1231-1omazenil to the BZ receptors of the human brain. Three patients suffering from partial epilepsy were examined on and off Vigabatrin medication, Immediately after injection of 152 MBq ~=Sl-lomazenil i.v. [Msllinckrodt Diagnostica] 12 slices of 5 rain each (128"128 matrix) located at 4 cm above the orbitomeatal line were acquired for 60 min, followed by a multislice study 120 rain after injection on a SME 810 multi-detector system. Uptake velocity and final binding of ~l-lomazenil was measured by drawing cortical ROle after correction for dose, bodyweight and decay. Within 15 minutes a steady state was reached. Between 15 and 60 min, measured at 5 min intervals, uptake did not change (P > 0.2, slope of regress'ran curve) for all curves individually. The uptake, after the steady state was reached, was significantly lower (44 SMU) for 2 of the 3 patients leach P < 0.001) when on Vigabatrin medication. After 150 rain counts in 6 slices gave an average decrease of 115 SMU off GVG to 105 SMU on GVG. Conclusion. High doses of GVG seem to have an apparent effect on ~al-lomazenil binding to cerebral BZ receptors in vivo. We conclude that patients with partial epilepsy referred for t~al-lomazenil SPECT in the detection of epileptic foci should temporarily withdraw from GVG medication. n-tAChR are possibly involved in epilepsy and may play a role in dementing processes. We address the issue of quantifying specific kinetic characteristics of these receptors in the living human brain. Dynamic and static single photon emission tomography (SPET) was quantitatively oefformed in 3 normal volunteers after intravenous injection of ~02 [-252 MBc 1 [123I]-4-iododexetimide (I-Dex), using a 4head SPET camera. The input function was determined and corrected for metaboIites using arterialized venous blood samples. Kinetic variables were extracted from the time activity curves of various braio structures using a 4-compartment model. The results (mear~+SD) are summarised in Table 1 These data support the view that after non-specific delivery to brain tissue (K1) I-Dex binds specifically (k3) to areas known to be rich in mAChR (cortex, caudate nucleus and to a lesser extent thalamus) but binds with a much lower affinity to structures with a low content of this receptor. The results validate the use of I-Dex for quantifying mAChR in the human brain in vivo. There are recent indications that GABAergic transmission may play an important role in MDD. However, little is known about the in-vivo activity of GABA receptors in depressed patients whereas many studies report about diminished cerebral blood flow and metabolism especially in the frontal lobe. Additionally, structural changes and reduced volume of the frontal lobe in patients with severe depression are described in CT or MRI studies. Thirteen patients ( 50-80 years) with a mean score on the Hamilton Rating Scale for Depression (HRSD) of 26 and without evidence of relevant physical illness, history of drug abuse or other preexisting psychiatric disorders were investigated. The DSM-III-R criteria for MDD were fulfilled. Iomazenil-SPECT was performed 90 min. and HM-PAO SPECT 20 n~. al~er i.v. injection. Uptake to 8 anatomically defined ROts of the frontal lobe (4 for each side in consecutive slices, 0.Tcm thick) was normalized to the cerebellum.An uptake ratio ~ 0,9 was determined to be pathological. Neuroradiological examination was done on a 2,0-T MRI-system using T~-arid T2-weighting and disclosed slight frontal atrophy in 6 patients. They all showed a diminished blood flow in one or more ROrs. Seven patients had a normal MRI and ttM-PAO scan. G.a~A receptor activity was diminished in 12 of 13 patients in the frontal lobe. Patients with normal HMPAO and abnormal Iomazenil SPECT were characterised by a lower HRSD-score than those with abnormal pattern in both investigations (22 vs. 29, n.s.) . In course of depression, reduced GABA receptor activity precedes disturbance of regional blood flow and anatomical changes of brain structure (MRI). Exept of 2 cases of chronic and severe depression, the extend of lesions in the Iomazenil SPECT exceed those ofHM-PAO SPECT. This observation confirms the GABAergic hypothesis of depression and may be of relevance for therapeutic studies especially in the earlier stage of MDD. Muscarinic receptors may play a significant role in neurological (Parkinson's disease, Alzheimer's disease, epilepsy) as well as in cardiac disorders (myocardial infarction, cardiac failure). In the present study we evaluated the biodistribution of [123I]-Iododexetimide (IDEX) in three healthy volunteers as a possible radioligand for the imaging of muscarinic receptors in both the human brain and the human heart. IDEX (specific activity > 5000 Ci/mmol) was synthesized in house and showed high specificity in an animal model. Three male healthy volunteers with an average age of 32 years received approximately 185 MBq i.v.. Dynamic images of the thorax were made during the first hour after injection (lmirdframe, 64x64 matrix). Static images were acquired until 9 hours after injection (5 mirdframe, 64x64 matrix). Whole body studies were made at 5, 9 and 24 hours after injection. Liver activity increased throughout the study: 5h post injection approximately 5 % of the injected dose was measured in the liver. Lung rapidly increased after injection and diminished 1 how after ad~finistration. The myocardium proved already well defined by 15 minutes after injection. Iteart to lung ratios reached maximum values 1.5 h after injection. At 24 h post injection, 2-3% of the injected dose was still present in the liver and brain. Heart and lung activity had almost :ompletely disappeared at that time. Cardiac SPECT images with a 3headed camera (60 angles, 20sec/frame, 64x64 matrix) were obtained lh p.i. and were of high quality. Myocardial uptake of IDEX varied from 513 to 5.7 Bq/ml/MBq injected (BORSOM program v 1.0). Maximum activity in the human brain was reached at 9 h p.i., which is in accordance with literature data Brain SPECT images (Strichman SME 810, Multislice, lcm/slice, 5min/slice, 128x128 matrix), were made at 9 h p.i.. From these in vivo studies in humans, we conclude that IDEX is a promising radioligand for the imaging of muscarinic receptors in the human brain and heart. Hepatocellular carcinoma (HCC) ist the most frequent hepatic malignancy and its early detection by conven-tional means is still very difficult. In recent years, (99mTc-NGA) has successfully been used as hepatocyte receptor-seeking radiopharmaceutical. to the signifi-cant higher number of insulin receptors expressed, HCC became visible as "hot spots" after injection of t23I-Tyr-14-insulin. In the same patients, 99"Te-NGA scinti-graphy clearly indicated "cOld spots" over CT-verified lesions au 5 minutes after injection. Good matching of "cold" and "hot" spots was observed. We conclude that our new double-tracer methodology using ~gmTc-NGA andlni -Tyr-14-insulin could be clinically useful in the early diagnosis of patients with HCC. Since October 1992, 6 patients (3 children and 3 adults) with hepatitis fulminans were treated with OALG in our hospital. One child received a second OALG because of primary non functioning first transplant. In these patients, 3 4 hepatobiliary scintigraphies (150 to 300MBq of 99mTc-Br-IDA) were performed including two phases : an angioscintigraphie phase of 60 2see-images and a functional phase of 40 lmin-images. In 3 patients (2 Children and 1 adult) scintigraphic examinations were performed systematically every ten days and the results were compared to clinical, biological and histological data. In the other 3 patients , seintigraphies were indicated if any vascular or functional complication was suspected either in the native or in the transplant liver. Quantitative evaluation of both phases permitted to assess separately the perfusion (arterio-portal index) and the function (uptake and excretion parameters) in each liver. For the native liver, scintigraphic data allowed to follow the process Of hepatocyte regeneration (size increase and functional recovery) within a delay of about 40 to 50 days. For the liver grat~, owing to scintigraphic results, we were able to evaluate the capacity of substitution function and to give valuable informations about the most usual dysfunctions (cbolestasis / rejection and anastomosis patenq¢). In 2 children functional recovery of the native liver was completed 2 months after OALG and a transplantectomy could be decided. In an adult patient, the regeneration and the function recovery were slower and 0nly a progressive decrease of immunoseppressant treatment was adopted. In the 3 remaining patients, transplantation was too recent and no definitive results were available. The diagnosis of sphincter of Oddi dyskinesia is usually based upon the positive prostigmine-morphine provocation (Nardi) test, which has been recently Improved by simultaneous measurements of the serum aspartate aminotransfarase (ASAT) levels. Due to the lack of the objective parameters, this test has long been criticized. In order to make Nardi test more objective we have tried to visualize the sphincter spasm by_quantitative hepatobiliary scintigraphy (QHBS). Methods: 22 eholeeystectomized patients, having, typical postprandial biliary pain were included in this study. Organic bfiiary and extrabiliary disorders were excluded. Sphincter spasm was evoked by 0,5 rag prostigmine and 10 mg morphine administration and visualiz .e# by QHBS using 140 MBq 99mTc-EHIDA. Digital images were obtained at one frame/rain, for 90 min. Time-activity curves were generated from regions of the liver parenchyma (LP), hepatic hilum (HH), common: bile duct (CBD) and duodenum. The time to peak activity (Tmax), the half-time of excretion (T1/2) and the duodenum appearance time (DAT) were calculated. Serum levels of ASAT were also determined. Results: From the 22 patients 12 responded with typical biliary pain and ASAT elevation -in 3 cases less than twofold -to prostigminemorphine provocation. The time-activity curves showed a marked biliary obstruction, and a significantly increased DAT. In 10 patients -4 indicated abdominal pare, but neither of them had enzyme changes -the time activity curves proved free transpapillary flow of the tracer and the DAT was normal. In patients with positive Nardi test the Tmax parameters of the HH and CBD (32.0+ 4.1; 62.8 + 4.7) were significantly increased when compared to the lq"ardi nega~i-ve group (19.6+1.0; 36.7+3.4). The Tl/2 parameters of the LP, HH, CBD and also the DAT were--also significantly increased in Nardi positive group ( Hypoxia is a frequent finding in end stage liver cirrhoses. The mechanism of production relies on preeapilar dilation and pulmonary a/teriovenous shunts. The aim of this work is to evaluate and quantify those shunts using 99mTcAlbuminmacroaggregates scintigraphy. Twelve liver graft recipients have been studied before and 2 months post-transplantation. Each patients received 5 mei (185 MBq) of 99mTc-AMA and subsequently 5 min scans of the head, abdomen and thorax were obtained. The percentage of shunted activity (SA) was quantified as previously described: Systemic activity = (head + abdomen)/0.39. SA = Systemic Activity/(System+Lung). Normal values < 6.0% (1). Results: Before grafting, 9 patients showed a SA < 6 %, 3 of them remained within normal values at 2 months posttransplantation while 6 of them increased to abnormal values (range 7.9 -28 %), none of them showed hypoxia.In the 3 remaining patients BA was > 6 % before grafting and normalized at 2 months, only one of these 3 patients presented hypoxia. Conclusion: Those preliminary results suggest the method's high sensitivity in quantifying pulmonary shunt, even in the absence of clinical hypoxia. The changes observed posttransplantation m a y b e due to the haemodynamic changes that follow the transplant. Nevertheless further studies are in progress to clarify the reason of those changes. Addition of 3% oxygen to the argon atmosphere within the Technegas generator results in production of a modified form of Technegas, "Pertechnegas", which is characterised by rapid lung clearance. Use of Pertechnegas for lung clearance studies has advantages over other radioaerosols in terms of delivery efficiency, radiation safety and patient acceptability. The aim of this study was to measure and compare Pertechnegas clearance in normal volunteers and in patients with established lung disease, in particular pulmonary fibrosis. Pertechnegas was administered using a single inhalation followed by a 5 second breathold. Dynamic acquisition commenced at inhalation using 1O second frames ( 64 x 64 matrix) for 30 minutes. Subsequent analysis following definition of regions of interest around the lungs produced a time-activlty curve to which a biexponential fit was applied. A half time for the fast component of clearance was then evaluated for the upper and lower zones and for the whole of both lungs. Results from ii volunteers and 13 patients studied to date reveal a more rapid mean clearance half-time (fast component) for patients with pulmonary fibrosis (n=6, mean t½=3.6mins, p=0.03) and for smokers (n=6, mean t½=3.6mins, p=0.06 ) compared to normal non-smoking volunteers (n=8, mean t½-=4.2mins) . Patients with pulmonary fibrosis exhibited more rapid clearance of radioaerosol from the lower zones of the lungs when compared to the upper zones whereas in smokers and normals the converse applied. No significant differences were found between normals and the other patient groups. It is envisaged that sequential measurement of Pertechnegas clearance may be of value to monitor clinical progress in fibrotic lung disease. Th. Krause 1, V. Siegerstetter 3, K. Thrombosis and intima proliferation of metallic stents are, at least in part, caused by platelet aggregation. Therefore, Tc-99m HMPAO labelled platelet scintigraphy of stent-shunt may clarify the mechanism and risk of shunt stenosis/occlusion. At the time of dilatation of the stent for TIPS (transjugular intrahepatic portosystemic stent shunt), 120-290 MBq of Tc-99m labelled autologue platelets were injected i.v. in 22 patients. Scintigraphic imaging was done at 20, 60, 90, 180 rain, 6 and 24 hrs. All patients had patent TIPS at the end of the procedure as assessed by duplex-sonography. Visual evaluation revealed no or minimal platelet accumulation in 11 patients, moderate accumulation in 5, and marked accumulation in 6 patients. The stent/liver ratio initially amounted to 1.69 (range 1.0-3.1) and was 1.42 (range 1.0-2.0) at 24 hrs. At the same time points the stent/heart ratio was 1.07 (range 0.6-1.8) with a maximum value of 1.13 (range 0.6-2.2) at 90 min. Accumulation in patient with Wallstent was more distinct without than with heparin (stent/heart ratio: 1.6 times, stent/liver ratio: 1,4 at 60 rain). Stent/liver ratio > 2.3 at 90 and 180 min was only found in all 4 patients in whom early thrombosis was proven duplex-sonographically at day 2. Tc-99m labelled platelet scintigraphy allows detection and quantification of early platelet aggregation at the stent. This technique may be of importance in the evaluation of the risk of stent occlusion and in selection of anticoagulants in patients with TIPS. The aim of the study was to investigate the behaviour of serum concentrations of intercellular adhesion molecule-l (ICAN-I) and P-seleetin (P-Sel) in conjuction with perfusion gamma scanning and lung injury score (LIS-Hurray et el. /19%/) in patients with ARDS. The study was performed in 8 patients with AROS caused by: multitrauma-4,sepsis-2,acute pancreatitis-l,burn-l. As control served 9 volunteers.Venous blood samples were taken in 12 hours intervals during the first three days and once daily during next 10-14 days or to death of patient (n=}).The concentrations of ICAM-I and P-Sel were determined by ELISA kits (88P,UK).The perfusion lung scintigraphy was performed following intravenous injection of Tc-99m microspheres (CIS,France) using gamma camera. The results showed continuous increase of ICAN-1 concentrations from slightly higher to about 5-fold of control in survivors and maintained high values from beginning of observation to the death of patients. The initial high levels of P-Sel in all patients decreased in the second week of disease in nonsurvivors and remained high for 3-4 weeks in survivors.ln all images many focal perfusion defects in periferal regions and decreased relative radioactivity in the low and middle zone of each lung were found. These abnormalites were more evident during the worsening of the patients state (increase of LIS value). The concentration of adhesion molecules may be a measure of excessive or inapropriate endothelial or leukocyte activation in the AROS.Alternations in perfusion may reflect leukocyte sequestration and releasing of vasoconstri ctors in lung vasculature. Obtained results may be useful for monitoring and prognosis in this disease. PULMONARY MICROVASCULAR pERMEABILITY FOLLOWS THE CLINICAL COURSE OF PATIENTS WITH THE ADULT RESPIRATORY DISTRESS SYNDROME (ARDS). ARDS is a major cause of morbidity and mortality in critically ill patients. Pulmonary vascular permeability measurements using radiolabeled proteins may be useful in identification of increased permeability during ARDS. We studied the transvascular passage of Gallium-67, considered to bind to circulating transferrin, as a measure of pulmonary microvascular permeability in 13 patients (female/male: 6/7, age: 47±18 yr, mean ±SD) within 72 hours after the development of ARDS. In 9 patients with a n improvement of the gas-exchange, defined as a reduction of the positive end-expiratory pressure (PEEP) level to 0 or extubation, the permeability measurement was repeated. Furthermore, 8 patients with congestive heart failure (CHF) and pulmonary edema were studied (female/male:O/8, age=67±lO yr). Kinetics of i.v. injected Ga-67 citrate (4 Mbg) and in vitro labeled red blood cells (Tc-99m, ii Mbq) were recorded in blood and over both lungs during 60 min, using probes. The pulmonary leak index (PLI) was calculated from the rate of increase in time, of the lung/blood ratio of the Ga-67/Tc-99m count ratio. The mean PLI ±SD of CHF patients was 10.4±3.9 lO'5.min "I and 11.9±2.9 in the left and right lung, ~espe~tively. The PLI of ARDS patients was 34.5±8.5 lO'~min'" and 34.2±7.7 in the left and right lung, respectively (p<0.O005 vs. CHF group). In the 9 patients with an improvement of gas-exhange the chest X-ray showed a reduction of pulmonary edema in 8 of the 9 patients while the arterial PO2/inspiratory 02 fraction ratio (P.Ch/FiO2) increased (p<0.01) from 146±58 at a PEEP level of llf5 cm H20 to 217±51 at a PEEP level of 0. KINETICS IN RELATION TO THE INTEGRITY OF THE ALVEOLOCAPILLARY BARRIER We used a double In-111/Tc-99m granulocyte labelling technique for the study of granuloeyte intravascular and extravascular kinetics in the lung in extrapulmonary inflammatory lesions. The pulmonary vascular granulocyte pool (PGP) and parenchymal migration were compared with inhaled DTPA aerosol clearance as an index of injury to the alveolocapillary barrier. Nentrophil activation was measured in vitro by a shape change assay [as (activated colls)/(total cells)]. PGP was measured by a first-pass integration technique using the Tc-99m signal, and expressed as a fraction of the total blood granulocyte pool (TBGP). Extravascular granulocyte migration was measured as the 24 hour pulmonary In-111 counts corrected for the chest wall bone marrow background. Compared with controls (0.09, SD 0.013, n=5), PGP:TBGP index was increased in extrapulmonary inflammatory conditions e.g. in inflammatory bowel disease (0.28, SD 0.07, n=7, p < 0.05), systemic vasculitis (0.33, SD 0.03, n= 6, p < 0.001) and bone marrow transplant recipients (0.30, SD 0.09, n=7, p < 0.001). PGP:TBGP correlated with granulocyte activation (r =0.76, p < 0.01). Granulocyte migration was increased in vasculitis (1.35, sd 1.11 cpm/pix/MBq, p<0.05, n=5) and bone marrow transplants (0.96, sd 0.50 cpm/pix/MBq, p < 0.02, n=5) versus zero in controls, but did not depend on granulocyte activation status. Nevertheless, the migration signal correlated both with T1/2 of the lung DTPA clearance curve (r=0.54~ p<0.05), and with fast clearance exponent (r=0.77, p<0.01). The fact, that inflammatory activation of granulocytes correlates with delayed transit through the pulmonary vascular bed, but not with extravascular migration argues in favour of endothelial factors in the regulation of granulocyte migration. On the other hand, an increase in PGP:TBGP is not in itself associated with alveolocapillary damage, which seems to require extravascular neutrophil migration. An increased lung clearance of Tc-99m-DTPA has been found in smokers and pts. wtih lung fibrosis and pneumocystis pneumonia. A decreased clearance has been documented for diabetic patients with vascular complications or proteinosis. Normally Tc-99m-DTPA is used for estimating an impaired epithelial integrity. Today a new imaging tracer Pertechnegas (Ptg) is available which is easy to produce and to deliver. After diffusion through the alveolar membrane it is rapidly washed out of lungs; the half time of the clearance (Tl/2) is =11 min in normal pts. After transplantation immunosuppression prevents a rejection of the organ. To evaluate the influence of long-term immunosuppressive therapy on lung permeability pts. with heart-transplants were examined. 20 non-smoking males (age: 51+10) and without any signs of rejection inhaled ==20 MBq Ptg. A dynamic study with 60 frames was acquired over a period of 15 mins and a monoexponential fitting procedure was done on the lung clearance curve. The clearance rate (Tl/2) was 13.6+_2.3 mins (range: 10.3 -19.1 ). There was a significant difference compared to a normal reference group. (n=12, T1/2=11.1+1.1 mins, range: 9 -13). The reason for that is unclear. Perhaps immunosuppression causes a thickening of the alveolar membrane. It may also be possible that the clearance is not solely dependant on diffusion but is linked to some active cellular functions which are reduced by immunosuppression, as well. The initial disease which had made transplantation necessary and the following rejection treatment must also be taken into consideration. The incidence of thyroid cancer in children from Belarus has increased after the Chernobyl reactor accident from 2-4 cases in 1986 to 66 cases in 1992. In April 1993, we started the joint Belarussian-German project "Scientists Help Chernobyl Children" on optimization of childhood thyroid cancer, which is sponsored by German electricity companies. From 1.4.93 to 28.2.94, 36 children with advanced thyroid cancer from Belarus have been treated with 1-131 in Essen. The 22 girls and 14 boys aged 7 -18 years (mean age 11.1 + 2.9 years); histology had shown 34 papillary and 2 follicular cancers. 31 cases had to be classified as pT4, 33 as pN1 and 25 as pM1 cancers respectively. Distant metastases were localized in the lung in 24 patients and in 1 patient in bone. Pulmonary metastases mainly were of disseminated, miliary type. Up to now 60 courses of high dose 1-131 treatment have been given to the children. Despite the fact that fractionated 1-131 treatment has not been finished, in all but one cases at least a partial response could be observed. However, in childhood thyroid cancer with disseminated lung metastases 1-131 induced pulmonary fibrosis may limit the maximum cumulative therapeutic activity of 1-131. With respect to the question of radiation carcinogenesis, biological dosimetry by micronucleus assays in peripheral blood lymphocytes revealed a higher frequency of abnormalities in cancer children as compared to a control group of children without cancer from uncontaminated areas of CIS countries. D. Huvsmans, A. Hermus, J. Barentsz, F. Corstens, P. Kloppenborg. Depts. of Nuclear Medicine, Endocrinology and Radiology, University Hospital Nijmegen, The Netherlands. We evaluated the anatomical and functional results of treatment with 1311 and L-thyroxine (L-T4) in patients with large, compressive multinodular goiters. 18 patients,16 females and 2 males, aged 65+13 yr (mean+sd; range 46-86 yr) were studied. 7 patients had previously undergone thyroid surgery. 131 I was administered as a single gift, aiming at 3.7 MBq retained per gram of thyroid tissue at 24 hours. After 1311 therapy (2.6+1.0 GBq; range 1.48-5.55 GBq), euthyroid patients (n=14) were treated with L-T4 in order to keep serum TSH levels <1.5 mU/I; for hyperthyroid patients (n=4) L-T4 was combined with methimazole. Before and 1 year after 1311 therapy, anatomical and functional parameters were evaluated in 17 of 18 patients (one patient had to be operated 10 months after 1311 therapy; thyroid volume reduction at that time was only 10%). Thyroid volume (TV) was measured with magnetic resonance imaging (MRI), using planimetry of serial slices. The smallest cross-sectional areaof the tracheal lumen (SCAT) was also determined with MRI. Exacerbation of obstructive symptoms after 1311 was not observed. Before treatment TV was 274+161 ml (range 109-825 ml; n=17). After one year, a volume reduction of 116+98 ml (range 24-444 ml) was reached (40-+15%; range 19-68%). Neck circumference diminished by 3+2 cm (range 1-8 cm). SCAT was 0.75_+0.37 cm2 (range 0.29-1.70 cm2) before therapy and 0.99£-_0.49 cm2 (range 0.30-2,19 cm2) after therapy (n=16). Mean increase of SCAT was 32+35%. In 12 of 16 patients SCAT increased more than 10% (range 13% to 124%). In the remaining 4 patients it virtually did not change (<5%). Significant improvement (i.e. >10%) of forced inspiratory volume in 1 second (FlY-l) was observed in 7 of 16 patients (range 11-48%). FIV-1 improved in 4 of the 6 patients in whom this parameter was clearly subnormal before therapy (the other 2 patients had vocal cord paralysis due to prior surgery). Symptoms of superior vena caval obstruction disappeared in one patient and elevated central venous pressure normalized in another patient. In conclusion, treatment with 1311 and L-T4 of patients with a large, compressive multinodular goiter resulted in a mean reduction of thyroid volume of 40% in one year. This was accompanied by improvement of compressive signs (tracheal compression, reduction of inspiratory pulmonary function, venous obstruction). 1311 therapy is an effective alternative in elderly patients who refuse surgery or in whom surgery is contraindicated. FEizy M., K S r n y e i J Two sets of micropuncture experiments were performed in rat kidneys in order to study the inaarenal handling of 99mTc-DMSA, and pertechnetate. In a first series the concentration profile of DMSA along the nephron was measured according to our earlier micropuncture protocol for MAG-3 (JNM 30:1986 , 1991 : Fluid from Bowmann's space of surface glomeruli as well as fluid from proximal and distal tubules was collected. Bowman's space urine contained only 15_+2% (n=8) of the Tc activity of arterial plasma, indicating very low filtration of DMSA likely due to high plasma protein binding (93%). The concentration ratio of tubular fluid to plasma was 0.31+0.4 (n=17) in the proximal tubulus and 1.13_+0.34 (n=5) in the distal tubulus suggesting the absence of secretion and reabsorption. In a second series surface loops of proximal tubules were micropunctured and perfused for 10 to 20 minutes with DMSA or pertechnetate dissolved in 0.9% saline (10 nl/min It is accepted that the radiochemical purity of 1-131-Hippuran (Hipp) used for ERPF measurements with the continuous infusion method with urine collection (with continuous infusion of Hipp over a period of hours) should be minimally 98% (ie the free 1-131-iodide (iodide) is maximally 2%). This is because iodide and Hipp cannot be counted separatly and in comparison with Hipp, iodide is excreted in urine to a lesser extent. Therefore in the formula ERPF = UxV/P (UxV= activity excreted in urine in time; P= plasma activity), iodide will contribute mainly to the denominator and will therefore lower the calculated ERPF. Iodide percentages below 2% could still have significant influence on calculated ERPF, therefore we investigated the influence on ERPF of labeled iodide impurities below 2% by adding known amounts 1-123-iodide to the infusion solution in clearance studies in 9 patients. 1-123-iodide was counted separately from 1-131-Hippuran in urine and plasma samples, and the influence of different percentages free iodide on ERPF was determined. It was found, as expected, that the percentage iodide in plasma increased during the infusion time and that the percentage iodide was higher in patients with higher ERPF (in which case 1-13f-Hippuran in plasma was lower). Examples of the influence of iodide: the influence of 2% iodide was substantial: in a patient with an ERPF of about 500 ml/min, 2% iodide resulted in a drop of ERPF of about 7% after 1.5h and of 13% after 5.5h. In this same patient 0.5% iodide resulted in a drop of ERPF of maximal 5%. We conclude that one should aim at a radiochemical purity of Hippuran of at least 99.5% since percentages iodide of 1 a 2% still have significant influence on ERPF, especially when ERPF is high. Tc-99m-Ec is a new renal agent introduced as an alternative substitute for OIH in evaluation of renal function. Comparative studies in humans have demonstrated that renal clearance of Tc-99m-EC is superior to that of Tc-99m-MAG3 with similar imaging quality. The present study was designed to evaluate the clinical usefulness of Tc-99m-EC in renal disorders using OIH as an intrasubject standard. 20 patients with various degrees of renal impalrement were received 100MBq Tc-99m-EC and 7.4MBq 131-I-OIH. After the injection 11 blood samples were obtained during 60 rain. and 0.2ml plasma samples were counted by a well type counter. Pharmacokinetic data were calculated using double compartment analysis (Sapirstein). 60 min. urine was collected and urine samples were also counted. Protein binding values were determined by ultrafiltration. Imaging were performed for 30 rain. duration (Siemens Basicam). The mean plasma clearence of Tc-99m-EC (264.3~130) was found lower than that of OIH (357q-174) (EC/OIH: 0.76) giving an excellent correlation with OIH (I=0.64). 60 rain. excretion of Tc-99m-EC was almost identical to that of OIH (50% vs 51%). The protein binding of Tc-99m-EC was almost half of OIH protein binding value (33% vs 61%) and red blood cell binding of EC was almost negligible with respect to OIH (3% vs 27%). The volume distribution of Tc-99m-EC was found slightly higher than that of OlH. The elimination of Te-99m-EC was found longer than that of OIH. Image quality of Tc-99m-EC was of course better than that of hippuran due to Tc-99m labeling. In conclusion Tc-99m-EC has excelent imaging charecteristics and its plasma clearence allows to estimate the accurate ERPK With its prompt availability and simplicity of preparation Tc-99m-EC can be used in routine renal imaging and functional studies. Prazosin related alfa 1 adrenoceptors have been known for a long time. Quinazoline derivative, doxazosin messylate (Cardura, trademark finn Pfiser) is also a competative postsynaptic alfaladrenoceptor antagonist, but with a longer half life time. Hypertensive patients were sent to our department for renography because their hypertension was supposed to be due to renal artery stenosis. Four of these patients were pretreated with antihypertensiv doxazosin. In all these cases pronounced changes in the renogrammes were found with doxazosin. In three cases the renogrammes showed reduced bilateral blood flow, prolonged peaktime and delayed excretion of the tracer (Tc99mDTPA) from the kidneys due to bilateral renal artery stenosis. In the fourth case similar results were observed in the fight kidney. The renogram of the left kidney was found to be normal. Renal angiography confnvned these results. 10 days after the removal of doxazosin new renogrammes were registered under the same conditions as with doxazosin, showing normal results.We believe that doxazosin also has some effect on the renin-angiotensin system and/or on the renalparenchyme. Renography should be avoided if the patients are taking doxazosin medication. On the other hand double renography without and with doxazosin as shown here may unmask renal artery stenosis. The incidence of deep-seated fungal infections has dramatically increased these last decades. As they are difficult to eradicate, acute and chronic renal toxicity are among the most common Side effects of a number" of conventional antifungal treatments. Early evaluation of renal functional insufficiency in the above patients is of clinical significance. The ability of 99mTc-DTPA to detect antifungal therapy nephrotoxicity has been investigated in the present experimental work. Toxic doses (LD100, LD50 ) of amphotericin B (AMB) have been determined in mice (Swiss SWR/De). Groups of mice intravenously treated by various AMB doses inferior to LD50 are weighed daily and urine biochemistry shows normal except protein level which is increased to 30 mg/100 ml. 99mTc-DTPA biodistribution studies are performed in the above groups of mice 2 hr afte~ the injection of AMB. One hour after the injection of the radiopharmaceutical the mice are sacrificed by an ether overdose. Blood samples, and the various organs are weighed. The urine excreted and the above organs are counted in a well-type counter with reference to a standard dose. After statistical analyses the results show that in a short time interval after AMB injection the blood clearance and urinary excretion are significantly delayed as a consequence of the acute toxicity of AMB. Two hours after 3.30 mg AMB/kg b.wt, the 99mTc-DTPA concentration in blood 1 hr after inj. is equal to 18.12+4.63% of injected dose compared to 1.86_+0.23% in controls, whereas excretion in urine is equal to 33.20_+6.18% of injected dose comeared to 90.81±3.54% in controls. The extent of disturbances in 99mTc-DTPA pharmacokinetics is related to AMB dose. In conclusion, the above results suggest that 99mTc-DTPA can be efficiently used in order to evaluate the degree of renal impairment induced by high doses of antifungal agents and to help in the follow-up of the above patients. The aim of this study was to assess the sensitivity of positron emission tomography with 18-F-FDG (FDG-PET) in the detection of pelvic lymphnode metastases of urogenital malignomas compared to x -r a y computed tomography (CT). 30 patients were studied; 20 patients presented with prostate cancer, 7 patients with bladder cancer and 3 patients with penile cancer. FDG-PET was performed in fasting state after bolus injection of 370 MBq 18-F-FDG with a PC 4096 PET-Scanner, Patients were scanned dynamically in one scanner position until 80 min poet injection, Additional static frames were aquired to cover the entire pelvic region. All patients recieved a pelvic or inguinal lymphnode dissection. Postsurgical histological examination revealed lymphnode metastases in 12 / 30 patients; two of the 12 patients affected had micrometastases (<]mm) only, PET detected focal lesions of high FDG-uptake in 10 patients, whereas CT detected suspicious lymph nodes in only 5 patients, Both FDG-PET and CT failed to detect metastatic desease in the two patients with micrometastases, FDG-PET detected lymphnode metastases in sigqaiflcantly more patients (ca, 80%) with metastatic desease than CT (ca. 45%) did, The data suggests that FDG-PET detects pelvic lymphnode m e t a s t a s e s of urogenital malignomas with a higber sensitivity than x -r a y computed tomography. Previous preliminary report has shown a neurotoxic effect of doxorubicin on the myocardium assessed by I123-metaiodobenzylguanidine (MIBG) scintigraphy.To further evaluate this doxorubicin-induced cardiac neurotoxicity we analyzed data from 36 patients (pts, 26 women, 13 men, mean age 53-+16 with various malignant diseases; 13 pts were receiving doxorubicin with a mean.cumulative dose 353~168 mg/m 2 while 23 pts were not on doxorubicin. Cardiac I123-MIBG uptake was assessed as heart to mediastinum ratio (H/M) obtained 4 hours after intravenous injection of 5mCi I123-MIBG. Ejection fraction (EF) by radionuclide ventriculography was 57%-+10% in pts on doxorubicin and 60%~6% in pts withOJt doxorubicin (ns). In control pts MIBG H/.M was 2,13±0,2 while in doxo.rubicin pts 1,76-+0,2 (p 16 mm in all patients. Septal wall thickness ranged from 13 to 27 mm, Posterior free wall thickness ranged from 12 to i9 ram. Mean left ventricular mass index was 199 gr/ni ~ (range 144 to 258), None of the patients had valvular stenosis or systemic hypertension. Antimyosin uptake was quantified by a heart to lung ratio (HLR). Ten athletes with physiologic hypertrophy at echocardiography were used as control group. Antimyosin uptake was observed in 10 patients (83 %). The pattern of uptake was diffuse in 7 and confined to portions of the ventricle in 3 (1 anterolateral, 1 septal and 1 apical). Mean HLR in the control group was 1.47_+0.09 (p=NS versus normal subjects). Mean HLR in the group of patients with features of hypertrophic cardiomyopathy was 1.87_+0.19, range 1.50 to 2.20 (p<0.001). A correlation was found between intensity of antimyosin uptake and ventricular mass index (r=0. 625, p<0.01) . Antimyosin studies may be useful in confirming the diagnosis of pathologic hypertrophy in patients with features of hypertrophic cardiomyopathy at echocardiography. Angiogenesis is the main detem~inant of breast cancer invasiveness and 99m~c MIBI uptake by inv~sive breast cancer has been already r~ported by us. Aim of this study is to establish if a corres~ ex~ between tumor-induced neoangicr3~nesis ~nd~ tumor uptake of 99m~c MIBI. 19 patients, i0 with node ~sitive (N+) and 9 with ncde negative (N-) breast cancer have been sturlied with 99m~c MIBI. Node positivity h~ been established by histol~gical exam of nodes after surgery. Angiogenesis has been ~ by ~ndothelial staining with anti factor VIII antibodies and microvessels counted by means of a Q~ntimet 500 device for histological i~ages ar~ysis. A c~t-off of 135 vessels/a~aq correspcr~ to 90% probability of spreading in ~he Weinder's logistic regression was established. %~o observers blindly classified 99mTc MIBI scans as positive or negative on the h~sis of the presence or the absance of tumor i~age. Tumor/heart (T/H) activity ratio was also m~gsured. Immunohistochemistry sho~ed 71.6 + 12.1 vessels/~q in the N-pts and 146.6 _+ 20.6 ves~/~q in the N+ pts (P < 0.01). All the N-pts had a MIB=-scan whereas all the N+ pts showed a MIBI+ scan. T/H ~tio was 0.266 _+ 0.035 in N-a~d O.367 _+ 0.23 in N+ pts (P < 0.01). 9/10 N+ pts had more than 135 vess/~q add 1 shc~ed 99 vess/~ %~%ich corresponds to 70% probabill{ of node metastasis in the Weinder's regression. In oonclusion ~ur study shc~4s that 99mTc MIBI uptake is an i~xlirect measurement of angiogenesis but by a clinic~! point of vim its sensitivity in detecting invasive cance/~ is higher than that of immu~stoch~ically measured angiogenesis. Planar scintigraphy of the breast with TI-201 was recently found to be useful in differentiating between malignant and benign lesions in patients presenting with a palpable mass. Systematic screening for breast cancer is recommended from the perimenopause onward, but mammography may be difficult to interpret. We therefore performed a prospective study on the subject~ using Tc-MIB1 and planar as well as tomographic scintigrams. In 120 females, a mammogram of each breast (with in doubtful cases, an ultrasunography) and seintigrams were performed within a 3-day period. The scintigrams were obtained 1 hour aider injection of 740 Mbq of Te-99m-MIBI, by means of 1 anterior static acquisition of 3 minutes and followed by a circular tomography of 25 seconds per step and with 32 steps over 180 ° anteriorly. Final diagnosis was obtained by means of a biopsy or by a clinical, mdiohigical and seintigraphic follow-up of at least 6 months. Four cancers were detected in this population, the 4 of them by mammography, 3 on scintigraphy (in both the planar and tomographic views). The patient with false negative scintigraphy presented with an in sita intraductal adenoearcinoma of less than 1 mm in diameter, whose mammographic suspicion was related not to the tumor itself but to the presence of micro calcifications in an adjoining focus of fibroeystic disease. Ten cases of false pasitlves were noted atter mammography with ultrasonography versus 4 cases in static scintigraphic images and 11 in seintigraphic tomograms. Finally, tracer uptake was sometimes found in axillary lymph nodes, particularly in tomograms and, mostly, on the side of the tracer injection (sub clinically paravenous?), there being no obvious reason to relate this finding to malignant invasion. Circular tomoscintigraphy using Tc-99m-MIBI does not seem, in this series, to be better than a simple anterior view, mainly because of reconstruction artefacts when using small tracer activities. Also, results of screening a larger series would obviously be of value. So far though, our data would seem to imply some clinical usefulness for this technique. Tailoring the extent of surgery in the individual woman with BC in relation to a prior knowledge of the presence or absence of axillary and other lymph node involvement is an unrealised goal, unmet by previous BCRIS. This study embodies the use of a breast cancer specific ICRF monoclonal antibody SM3: the Tc-99m label; and the application of kinetic analysis with probability mapping which had previously prospectively detected lesions down to 5mm in ovarian cancer. 9 patients have received 600 MBq Tc-99m SM3 IV up to i0 days prior to subsequent surgery. Anterior and lateral gamma camera images of the breasts and axilla were made at l0 mins, 6 and 22h, with marker images with Co-57 for the subsequent image repositioning protocol. Application of the change detection algorithm gave sizes of significant change between the early nonspecific distribution and the later images with sites of specific SM3 uptake. In this way, image positive and image negative axillary nodes as well as the primary BC have been collated with subsequent surgical and histological findings and are correct in 8/9. Apparently involved internal mammary nodes have been imaged, but with no surgery co confirm. These initial results are encouraging and are the basis for a formal clinical trial. McEwan A ~, MacLean G ~, Golberg L z, Akram 11, Boniface G 2, McQuarrie S 1 , Golberg K 1 , Sykes T 2, A m y o t t e G 1, Noujaim A. z 1, Cross C a n c e r Institute a n d 2, Biomira, Inc., E d m o n t o n , Alberta C a n a d a . EVALUATING RADIOIMMUNOSCINTIGRAPHY IN PATIENTS WITH BREAST CANCER. R a d i o i m m u n o s c i n t i g r a p h y (RIS) h a s b e e n p o s t u l a t e d as h a v i n g a role in t h e m a n a g e m e n t of p a t i e n t s with b r e a s t c a n c e r b o t h at p r e s e n t a t i o n a n d at r e c u r r e n c e . We h a v e p e r f o r m e d a P h a s e II t r i a l of a m o n o c l o n a l a n t i b o d y (MAb) to assess its p o t e n t i a l role in this clinical setting. MAb 1 7 0 H . 8 2 ( T r u -S c i n t ® A D TM B i o m i r a Inc) is d e r i v e d a g a i n s t s y n t h e t i c TF a n t i g e n a n d i n -r i v e r e a c t s with m o s t a d e n o c a r c i n o m a t a a n d h a s b e e n directly labelled w i t h T c -9 9 m . F o r t y p a t i e n t s w i t h p r i m a r y o r m e t a s t a t i c b r e a s t c a n c e r h a v e b e e n i n c l u d e d in this e v a l u a t i o n . Doses of 1 mg. (21 pts), 2 rag. (10) a n d 4 mg. (9), labelled with b e t w e e n 1 1 0 0 a n d 1 6 0 0 MBq of T c -9 9 m , w e r e a d m i n i s t e r e d b y s l o w i n t r a -v e n o u s a d m i n i s t r a t i o n . I m a g e s w e r e o b t a i n e d i m m e d i a t e l y p o s t injection a n d at 4-6 a n d 1 8 -2 4 h r s p o s t injection with a GE 4 0 0 AT o r Prism 2 0 0 0 g a m m a c a m e r a . SPECT w a s p e r f o r m e d a t 2 4 h o u r s . P h a r m a c o k i n e t i c a n a l y s i s was p e r f o r m e d o n 4 p a t i e n t s a n d i n c l u d e d serial b l o o d s a m p l i n g a n d total u r i n e collection to 72 h o u r s post injection. E i g h t y -f i v e b r e a s t , n o d a l a n d b o n e sites w e r e i d e n t i f i e d as k n o w n lesions. E i g h t e e n of 20 b r e a s t lesions w e r e identified, 36 of 4 0 l y m p h n o d e s a n d 23 of 28 b o n e m e t a s t a s e s . In total, five false positives w e r e identified, 3 of w h i c h w e r e in t h e b r e a s t , 1 in t h e i n t r a -m a m m a r y c h a i n , a n d o n e in the axilla. S e n s i t i v i t y f o r l o c o r e g i o n a l soft tissue disease was 9 0 % a n d specificity 93%. These d a t a s u g g e s t h i g h clinical a c c u r a c y f o r this MAb in this g r o u p of p a t i e n t s a n d i n d i c a t e a p o s s i b l e r o u t i n e c l i n i c a l m a n a g e m e n t role for RIS in b r e a s t c a n c e r m a n a g e m e n t . In this continuing study the in vivo scintigraphic imaging of somatostatin receptors in mammary tumors is studied utilizing lliln-DTPA-Octreotide in order to evaluate this technique for both preoperative detection of the extent of the disease and postoperative follow-up for possible recurrence. A total of 24 female patients (mean 55,07y, range 27-67y) with diagnosed or suspected breast tumors were studied. All patients had findings in preceding studies with mammography and/or U/S. CAT, MRL Following the IV administration of 2,2-3 mCi lilln-DTPA-Octreotide, planar imaging (and SPECT selectively) was carried out at 6+i and at 22+2 hrs p.i. The scintigraphic data was compared to the histological data (procured by FNA / node biopsy or tissue removed by surgery}. The prestudy grading was as follows: grade IIA (n=3), grade lib (n=4), grade Ilia (n=5), grade 1lIB (n=6) and grade iv (n=6). The scintigraphic imaging was then evaluated in view of these findings for a possible correlation between the grade and the imaging and also to assess whether imaging could detect local or distal recurrences of the disease. In 20 of the 22 patients with cancer imaging was positive (sensitivity 90,9%), In two patients (8,3%) the scan was falsely positive (histology revealed fibroadenosis). In 2 other patients (grades liB, IliA} the scan was false negative (8,3%), Pieural effusion was imaged in one patient where aspiration and subsequent cytology revealed malignancy. Bone metastases were imaged in 5 patients (confirmed by 99mTc-MDP scintigraphy]. The normal biodistribution of the radiopharmaceutical in the liver, the spleen and the kidneys hindered the imaging of possible hepatic metastases, In two of the patients however formerly unknown metastatic lesions were imaged in the abdominal region. In 8 of the 22 true positive scans (36,4%) previously unknown involvement of maxillary and/or thoracic lymph nodes was demonstrated which had either not been detected or not been confirmed previously by other modalities. 111-ln-Octreotide proves to be an important radio-pharmaceutical in the diagnostic imaging of breast cancer. Its ability to image involved lymphnodes and both local and dist31 recurrence has been helpful in the grading of the patients and especially those with grades I]IA-lilB with the relevant c)inical significance. Short-comings of this procedure is.the fact that a benign fibroadenoma was imaged thus lowering the specificity, and the high cost of the radiopharmaceutical which prohibits its everyday use. The introduction of a larger number of patients in this continuing study and the use of $PECT is expected to provide more objective conclusions, PET-FDG imaging has been shown to accurately identify large breast tumors, but little PET data exist in the initial diagnostic workup of small breast lesions detected by mammography. Twenty-one patients scheduled for exploratory breast surgery were studied with FDG-PET (Siemens ECAT 951R). Dynamic FDG-PET scans of the breast were obtained for 60 minutes followed by PET imaging of the axillas for 15 rain. Time activity curves were evaluated and standardized uptake values for FDG calculated based on attenuation corrected images acquired between 45 -60 rain after tracer injection. Twenty-two malignant lesions in 17 patients could be identified with FDG-PET (SUV 3.6_+1.8). An increased FDG uptake (SUV 3.4 and 3.8) was found in two patients with a carcinoma in situ. Benign lesions such as mammary dysplasia (n=5) and fibroadenomas (n=2) showed a significant lower FDG accumulation (SUV 1.3-+0.2) than malignant tumors (p<0,01). Tumor FDG uptake correlated with in-vitro human nuclear cell proliferationassociated antigenbinding (Ki-67) in tumor tissue of 11 patients. Axillary lymph node dissection in 15 patients showed in 7 cases axillary lymph node involvement. True positive FDG uptake was seen in 4 patients. 3 patients had false negative findings with lymph nodes size smaller than 1 cm in diameter. In conclusion, FDG-PET imaging identified all malignant lesions in this selected patients. Fibroadenomas and areas with mammary dysplasia had significant lower glucose metabolism. The observed high specificity has to be confirmed in a larger patient population with benign tumors. Detection of lymph node involvement appears to be limited by partial volume effect. FDG-PET may be clinically useful in the early diagnostic workup of patients with abnormal marnmography. (WD) is a hereditary disorder of copper metabolism leading to striatal degeneration and liver cirrhosis. It may be treated either by decoppering drugs such as D-penicillamine (DPA) or by liver transplantation (IT). The aim of this study was to evaluate the effect of these therapeutic modalities on striatal glucose consumption (rCMRGIc). Using FDG and the PET-camera PC-4096 the striatal glucose consumption was measured in 25 normal volunteers and 14 WD patients. In 3 of the patients LT had been performed 1 to 6 years before their inclusion in the study. I1 of the patients were treated by DPA. Whereas in 4 of these decoppering therapy had just been started before the PET study, the duration of DPA therapy was longer than 5 years in the remaining 7 patients. The normal limits of striatal rCMRGlc were calculated as 95% confidence limits of the normal data using Student's t-values. While striatal rCMRGlc was markedly reduced below normal in tbe 4 patients with short duration of DPA therapy, it was in the lower normal range in the patients with long-standing medication. In the latter group striatal glucose consumption correlated negatively with the duration of medication and the urinary excretion of copper (p<0.01). The patients in whom LT had been performed also had normal values of striatal rCMRGlc. In conclusion, DPA medication leads to a normalization of striatal glucose consumption in WD patients; the observed negative correlation between striatal glucose consumption on the one hand and the duration of medication and the urinary excretion of copper on the other suggests that the dose of DPA given in the patients studied was inappropriately low. There was no decrease of striatal glucose consumption after LT; this is in agreement with the recent theory of a disturbance of the biliary excretion of copper as the cause responsible for the excessive tissue copper accumulation in WD. K. Scheidhauer A. Scharl ~,T. Oepen * , E . Voth, P. Thei:ssen, K. Schom~icker, A. Bolte*, H. Schicha Departments of Nuclear Medicine and Gynecology* University of Cologne, Germany. [18F]-FDG-PET IN BREAST TUMORS Aim of the study was to evaluate Positron emission tomography (PET) using [18F]-Fluorodeoxyglucose (FDG) for visualization and detection of breast tumors. Although unspecific, higher rates in glucose metabolism compared to normal tissue should enable selective tumorimaging. Therefore, in 23 patients, 12 with unclear breast findings and 11 breast cancer patients suspicious for metastatic disease, FDG-PET was compared to histology and other imaging methods. PET was performed after iv-injection of 370 MBq [18F]-FDG in fasting state on a CTI ECAT Exact scanner with an axial FOV of 16.2 cm, transmission and emission images were taken 15 -45 min. p.i., with additional whole body scans in some metastatic patients (n=4). Focally increased uptakewas visually judged suspicious for malignancy. PET yielded focal FDG-uptake with high contrast in 7 of 8 primary carcinomas including a patient with only monomorphic microcalcifications. In another patient, only PET correctly visualized multifocal disease (3 foci, ~ 0.4 to 1 cm). One carcinoma in a diabetic patient was not seen (false negative). A clinically suspicious cicatrical tissue after tumorectomy (lymphoma) and chemotherapy was false positive (low contrast). All metastases (lymph nodes, lungs, brain, bones, soft tissues) seen by other methods (X-ray, CT, MR, bone scan) showed FDG-uptake. In 3 patients, only PET initiated further diagnostic procedures. These results indicate, that FDG-PET may provide a fast diagnostic study (30 -60 min.), which allows a o n etime accurate tumorstaging of several organ systems for primary tumor and metastases. Whether early use of FDG-PET in cases of unclear breast disease and for staging in breast cancer benefits patients, needs to be demonstrated. Posttraumatic Parkinson-syndrome (PPS) can occur after severe head injuries with inner inferior cerebral trauma. L-DOPA-therapy can be helpful in some cases, while others show no response. Considering the pathogenesis of this syndrome either a destruction of dopamine-receptors (DR) in the striatum or a disruption of neural transport systems could be responsible for PPS. To analyze mechanisms responsible ffor PPS we studied 5 pts. with PPS doing 99mTc-HMPAO-perCusion-SPECT and 123 I-IBZM-D2-recep~ tor-SPECT 1 week after the perfusion study and after apomorphine tests. SPECT-images were obtained with a single-head-rotating-camera 10 min. p.i. of 555 MBq 99mTc-HMPAO and 2 hrs. p.i. of 185 MBq 123 I-IBZM. 3 pts. were also studied after L-DOPA-therapy ffor 6 weeks and after L-DOPA had been withdrawn for 7 days. All pts. showed perfusion defects (4 bilateral) initially, in 4 cases also in the striatum (2 bilateral). IBZM-SPECT showed uptake defects in basal ganglia only in 4 pts. (i bilateral) of which i had the defect in the contralateral side of the perfusion defect. Control scans in 3 pts. showed normal IBZN-uptake in all pts., which had all improved under L-DOPA-therapy. Our findings suggest that HMPAO-and IBZM-SPECT together with apomorphine tests can predict the response to L-DOPA-therapy in pts. with grossly abnormal perfusion scans but with at least partially functioning DR. Tc-99m HMPAO SPECT Brain Perfusion (BF) imaging is more sensitive than X-ray CT or MRI in detecting abnormalities following closed head injury (HI). The purpose of this study is a retrospective comparison between the findings of SPECT BP imaging and X-ray CT or MRI in two groups of patients who suffered from minor to moderate closed HI. All had T c -~m SPECT BP one hour following I.V. injection of 30 mCi (IIIOMBq) and were imaged either early within one week; 21 patients (Grp I), or late 3 weeks to one year; 21 patients (Grp II). All had either eT or MRI. The results are in the following We conclude that early SPECT BP imaging (within one week) following closed HI is more sensitive than delayed imaging (more than three weeks). This is due to recovery and repair of lesions detected in early imaging. We encourage EP imaging following minor to moderate head injury in the first week. This might help explain the psychological and behavioral complaints of these patients in the absence of CT or MRI abnormalities. An ideal project would be to follow up the same group of patients with early and delayed BP imaging and to correlate with neuropsychological testing. U. Cremerius, I. Lossau, B. Lippitz, J. Weis, J.M. SchrSder, J. Gilsbach, U. BUll Depts. of N u c l e a r Medicine, N e u r o s u r g e r y and Neuropathology, R W T H Aachen, G e r m a n y The aim of our study was to e v a l u a t e the r e l e v a n c e of T c -H M P A O -S P E C T (reflecting vascularisation) and F D G -P E T (representing glucose consumption) for a n o n -i n v a s i v e g r a d i n g of i n t r a c r a n i a l m e n i n g i o m a as c o m p a r e d to h i s t o p a t h o l o g i c a l grading. 30 p a t i e n t s w i t h i n t r a c r a n i a l m e n i n g i o m a r e c e i v e d SPECT 15-60 min. p.i. (750 M B q 99m-Tc-HMPAO) and . 26 m e n i n g i o m a s w e r e c l a s s i f i e d as g r a d e 1 (WHO), 4 as g r a d e 2 or 3. SPECT was e v a l u a t e d s e m i -q u a n t i t a t i v e l y u s i n g the tum o r / c e r e b e l l u m -r a t i o (TCR-HMPAO) and the tumor /grey m a t t e r -r a t i o (TGR-HMPAO). G l u c o s e cons u m p t i o n (MRGIu) of m e n i n g i o m a was a s s e s s e d from static P E T -s c a n s a c c o r d i n g to SOKOLOFF. T 39±.15 s *in ~m o l / g / m i n ( n ) s = ( n o t ) s i g n i f i c a n t for p<.05 Grade 2-and 3 -m e n i n g i o m a s r e v e a l e d higher M R G I u and H M P A O -u p t a k e t h a n t y p i c a l g r a d e lmeningiomas. The In order to reveal in v i v o signs of neuronal d a m a g e in MS as a p o s s ib l e e x p l a n a t i o n of the chronic progression, we p e r f o r m e d C o -P E T and MRI on a g r o u p of 7 r e l a p s i n g -r e m i t t i n g M S -p a t i e n t s (no immunos u p p r e s s i v e therapy) and a g r o u p of 7 h e a lthy s e x m a t c h e d volunteers. The p a t i e n tg r o u p s h o w e d an i n h o m o g e n e o u s C o -d i s t r i b ution t h r o u g h o u t the brain, s u g g e s t i n g focal a c c u m u l a t i o n in m u l t i p l e spots. There was a s i g n i f i c a n t l y i n c r e a s e d n u m b e r of C o -s p o t s (as c o m p a r e d w i t h the h e a l t h y brain) in the MS-brain, w h i c h s h o w e d partial a n a t o m i c a l c o r r e l a t i o n w i t h the M S -l e s i o n s as d e t e c t e d w i t h MRI. T h e r e was no c o r r e l a t i o n b e t w e e n C o -u p t a k e and c o n t r a s t -e n h a n c e m e n t on MRI. In conclusion, our p r e l i m i n a r y C o -P E T data suggest neuronal d a m a g e in M S -p a t i e n t s w h i c h c o u l d e x p l a i n the slowly p r o g r e s s i v e course in the later stage of the disease. RCBF IN HEROIN AND POLYDRUG ADDICTS EVALUTED BY 99mTc-HMPAO-SPECT: TEMPORAL LOBE INVOLVEMENT In drug addicts, namely in cocaine abusers, PET studies have revealed metabolic abnormalities. However, the effects of heroin dependence on cerebral perfusion have not yet been investigated systematically. We evaluated 37 in-patients by means of 99mTC-HMPAO-SPECT (40 investigations). HIV testing was negative in all individuals. Five patients were dependent only on heroin. Twentythree additionally took cannabis, 22 benzodiazepines or barbiturates, 11 cocaine, and 9 amphetamine. In addition to visual evaluation, 31 ROIs were drawn for semiquantative analysis. Both temporal and frontal regions showed the most striking blood flow abnormalities with right-sided preponderance. Thirty patients (75 %) had a hypoperfusion. Among them, the right temporal lobe presented with reduced blood flow in 32%, the left temporal region in 18%. A decreased perfusion of the right frontal lobe was observed in 11%. The right parietal and the right oceipital areas were involved in 9%. -Furthermore, combined addiction of cocaine and heroin significantly correlated with hypoperfusion of the right frontal lobe (p < 0.01). Abuse of amphetamines along with heroin was related to left lateral temporal hypoperfusion (p < 0.005), that of barbiturates along with heroin with left mesial temporal hypoperfusion (p < 0.005). However, there were no major perfusion differences when comparing polydrug addicts and individuals dependent only on heroin. Thus, our most striking finding, the hypoperfusion of the right temporal lobe in heroin (heroin alone or combined with other drugs) addicts, seems to be related to the heroin abuse itself.-In conclusion, the results presented here indicate abnormal cerebral perfusion patterns in heroin addicts predominantly of the right hemisphere. The preponderant right temporal lobe involvement might be related to the marked opiate receptor density of that region. We applied Fourier analysis to condensed images of gastric emptying with the aim to evaluate the amplitude (amp) and frequency (f) of gastric contractions. Patients with various gastric disorders were studied to assess the diagnostic value of the new approach. In 9 controls and 40 patients conventional gastric emptying studies (TAC, emptying rate, Tla) were performed using semiliquid and solid (10/49 pts) test meals. In addition for defined time intervals condensed images from a gastric ROI were established (space-and time matrix consisting of 160 frames with 3 see/frame) which were used to characterize gastric contraction parameters by Fourier analysis. Condensed images of gastric emptying precisely depicted the regio- 3,2 min-l). No significant correlations were observed between gastric emptying (Tla, emptying rate) and corresponding contraction parameters. In conclusion, Fourier analysis of condensed images has shown to be a feasible approach for evaluating gastric contractions in an easy, quick and reliable manner. Amplitude rather than frequency seems the relevant criterium to discriminate between various disorders. Quantitative results have shown to be independent of the composition (semiliquid vs. solid) of the test meal. Data on gastric contractions evidently expand the information provided by conventional emptying studies. R. Benti, *D. Lisciandrano, A. Bruno, *A.R. Baldassarri, E. Reschini, P. Gerundini Depts. of Nuclear Medicine and * Gastroenterology; Ospedale Maggiore and University of Milan, Milan, Italy SCINTIGRAPHIC ASSESSMENT OF RETROGRADE SPREAD AND ABSORPTION OF A 5-AMINO-SALICYLIC ACID ENEMA IN ULCERATIVE COLITIS AND ILEO-RECTAL ANASTOMOSIS 5-Aminosalicylic acid (5-ASA) enema is frequently given for topical treatment of the rectum in ulcerative colitis (UC) and ileo-rectal anastomosis (IRA).In IRA a significant Retrograde Ileal Spread (RIS) of a 5-ASA enema can unproperly increase its serum levels, being seven fold higher 5-ASA transport efficiency in ileal than rectal mucosa, lleo-rectal ripartition and absorption of a 5-ASA enema were investigated by nuclear imaging and measurements of 5-ASA plasma levels in seven IRA patients (age 22-68 ys) with UC in remission. Two grams of 5-ASA in 50 ml enema were mixed with 30-40 MBq of 99mTc colloids and administered. Dynamic images (1/min) of the abdomen in anterior view were obtained for 1 h, static (1 rain) images from 2nd to 6th hour. Semiquantitative analysis was performed obtaining an Ileal Percentual Activity (IPA) from ROls drawn over the ileum and rectum. Two patterns of rectal wall contraction were recognized in 1 st hour images: A) parietal rectal motility with RIS (2-1 l/h, mean 3.8); B) parietal rectal motility without RIS (9-21/h, mean 12.1).5-ASA plasma levels were measured with HPLC before, 30, 60 min and hourly for 6 h after administration. 5-ASA absorption was expressed by the integral Area Under time/plasma level Curve (AUC) in lag/ml/h. Mean IPA were 14.5+16 % and 8.7+6.1%, mean AUC values were 0.5+_0.2 and 4.3+3.8 in the 1st hour and 2nd-6th hours periods respectively. IPA and AUC values during the 1st hour were positively correlated (Spearman rank test, p=0.03) but not in 2nd-6th hours period. First hour AUC were lower in IRA than in a control group previously studied.Two IRA patients showed higher AUC than normal whereas three had lower AUC values.Patients with more than nine RIS/hour had the higher AUC values. The technique detects RIS presence and degree of a 5-ASA enema by quantitative parameters, revealing the rectal motility as a major cause of RIS related high 5-ASA absorption in topically rectal treated UC patients wih IRA. Severe acute attack is a life-threatening complication of ulcerative colitis (UC), generally suspected on the basis of available clinical and analytical data. Diagnosis is currently established on barium enema and colonoscepy, but with high risk of complications such as colonic toxic dilations or perforations. In 7 pts out of 36 with known or suspected UC, we have diagnosed severe attacks by 99mTC HMPAO labelled granulocyte scan, demonstrating a "double track" aspect. In all 7 cases, severe acute attack was confirmed by surgery and histologic findings. In the other 29 pts without severe attack, we never saw this "double track" aspect. Scintigraphic "double track" appears t o be pathognomonic of this disease. We explain this phenomenon by the morphologic modification of the inflammatory process which becomes transmural in the colonic wall in case of severe attack of UC. We conclude that 99mTc HMPAO labelled granulocyte scan is a reliable procedure for the diagnosis of severe acute attack of UC. This method is useful as a diagnosis tool, being easy to perform, fast and without risk of complication. Those who had had surgery were excluded. Patients with Incont were older than those with IBS or CConst( m e a n age 57, 44 & 42 respectively, p<0.05). There was no d i f f e r e n c e in the a n a t o m i c a l m e a s u r e m e n t s b e t w e e n the three groups, but the functional m e a s u r e m e n t s in p a r t i c u l a r b e t w e e n CConst and other two groups Increased FDG-uptake is a typical PET-finding in malignam rumors and has been observed in inflammatory disease, too. Recent reports upon differentiation between chronic pancreatitis and cancer seem to contradict these results. Purpose of the present study was to compare FDG-uptake measured in 30 patients with malignant (n=21 ) or benign (~--9) pancreatic tumors with histology of surgical specimens and proliferation evaluated by Ki-67 immunohistochemistry. Static PETscans were performed 40-70 min. afler iv injection of 150-300 MBq FDG and quantitated by calculating differential uptake ratios (DUR) of the tumor area shown by CT. Significant differences were found between high, intermediate, or low grade carcinomas (GI: 4.34-1.1; G2: 6.2.~0.7; G3:t0.34-2.1 [DUR]/p<.05) while the correlation between FDG-uptake and proliferation was poor (~--0.65). Tumor size did not influence the magnitude of FDG-aecumulation. Chrortie pancreatitis present in 8 patients was characterized by low FDGuptake (DUR: 3.0-a:I.2) except for one (DUR: 5.2). Surgical specimens of the latter revealed leukocyte-rich tryptical necroses as sign of active inflammation. In a patient with rapidly proliferating retroperitoneal fibrosis and vast lymphocytic infiltrations a high DUR of 7.9 was calculated and misinterpreted as sign of malignancy. We conclude that FDG-uptake of pancreatic cancer is strongly influenced by tumor differentiation, less by proliferation suggesting the presence of further edlular determinants of metabolism (e.g. glucose transporter proteins). Leukoeytie or lymphocytic infiltrations are the main reason for increased FDG-aceumulation in benign conditions. 111 J. Andersson, J. Bosaeus, B. L~ngstrSm Uppsala u n i v e r s i t y PET-centre, Uppsala, Sweden. Movements during or between PET examinations is a common problem causing difficulties in the interpretation of data. A method to detect and correct such movements is presented. The method maximizes a "similarity function" between two data sets. It uses derivative information from the image sets to determine which parts that contain orientational information and then uses the image correlation between these parts. It has bee n validated by applying a known set oftranslations and rotations to datasets collected from the same subject in the same position. The data sets have been collected either using the same tracer in both, tracers with a similar uptake pattern or tracers with a markedly different uptake pattern. The results show that for image sets with the same or similarly behaving tracers it is possible to correct for motions with a precision of 0.2mm and 0.2 ° . This precision is achieved for data sets with down to 0.5 million counts. For tracers with such marked differences in uptake pattern as water and NMSP it is still possible to reorient the image sets with a precision of 1.0mm and 1.0 °. The method is fast, and completed in 1-2 minutes of CPU time on a VAX-station 4000/60. Our results show that the method is adequate to use routinely to register image sets before usin 9 subtraction techniques, to register frames withln a dynamic sequence to yield accurate TACT-curves and to register examinations performed with different tracers to facilitate the analysis of multi tracer protocols. LS was performed during the first week of hospitalization (mean: 4.3 days). Mixed, autologous leukocytes, labeled with 99mTc-HM-PAO in vitro were used. The uptake in the view of the pancreas was classified as none, moderate or intense. Clinical features, laboratory parameters (the baseline amylase level and the amylase level 10 days following LS) and the outcome were registered during hospitalization. In group 1, 11 of the 22 LS proved positive. 4 of these cases had infected pancreatic necrosis, confirmed by surgery; other patients were successfully treated with antibiotics. The grade of leukocyte accumulation correlated with the duration of hospitalization (r:0.45, p<0.05) and with the late amylase level (r:0.57, p<0.01). Baseline laboratory findings showed no correlation with these parameters. In group 2, 4 patients had positive LS; 3 of them were operated on, and pancreatic abscess was detected in all cases. In 3 of the 7 cases with normal LS, surgery revealed a noninfected pancreatic pseudocyst. Conclusion: Leukocyte infiltration into the pancreas can be demonstrated by LS. Positive LS indicated a severe course of acute panereatitis, with a special need for antibiotic and/or surgical treatment. LS was also useful for differentiation between infected and noninfected psuedocysts in chronic pancreatitis. Classical Positon Emission Tomography (P.E.T.) enables to reconstruct either transverse slices of the object in a 2D mode, or directly a whole volume in a 3D mode. In both cases, the reconstruction process need to get projections of emission measurements all around the object (or patient). These projections are obtained over 180 ° either with many detectors in a ring arrangement around the patient, or with detectors facing only a part of the circumference and rotating around the patient. The new method called P.A.T. enables to reconstruct directly longitudinal slices Of the object without every projection around it. This is realized by using only a sub set of projections with respect to the sub normal direction (typienlly from 20 ° to 40°), including the T.O.F.set information. Events so located are then backprojected using a special mode, in order to reconstruct directly the emission information within ~he object volume. Comparing to the normal projection, the use of oblic projections allows a sensitivity gain with a loss of spatial resolution reduced with the time of flight measurement. An analytic study and a numerical simulation have been performed which enable to quantil~ for a final spatial resolution of 7 mm (intrinsec spatial resolution of 6 mm) a sensibility gain superior with a ratio 20 (comparing to an acquisition without time of flight) with time of flight measurement of 250 ps. We conclude that T.A.P., thanks to to the T.O.F. information an the plans reconstruction process enables to reconstruct correctly data volumes for WBI, in agreement with the aimed spatial resolution. This technic could dramaticaly reduce the price of the detection system of a PET for WBI applications. E.Rota Koos. H. Herzog, H.W. MUllcr-G~rtner Institute of Medicine, Research Centre Jiilich, and Nuclear Medical Department, Heinrich-Heine-University Dtisseldorf; Jtilich, Germany Blank and transmission measurements are necessary for attenuation correction of PET data.. The aim of the present study was to investigate the influence of the transmission source activity, e.i. of the number of transmission coincidences, on the quantitative accuracy of reconstructed PET images. The study was performed with the PET-Scanner PC4096-I5WB. A first phase was based on phantom measurements in form of brain simulation, the results of which have been already shown elsewhere. The second phase consisted of patient measurements: five brain studies and four heart measurements. Different transmission scans collected 0.5 to about 12 million coincidences. In case of brain studies, Regions of Interest (ROI) were drawn on whole cortex, thalamus, and white matter; for the heart studies one ROI was drawn on the myocurd. The results of the phantom measurements were confirmed by the patient studies. With transmission coincidences of -> 2.5 million per slice for the brain (left figure) and of -> 6 to 8 million for the heart measurement (right figure) constant values of activity concentration with a variance up to +/-6% were found. The corresponding standard deviations yielded values up to about 20% variance for brain studies, but of only 1% for heart measurements. For lower values than 2.5 and 7 million of coincidences, respectively, the results confirmed again the phantom measurements: the reconstructed images showed lower concentration values with higher standard deviations, but also image artifacts, due to an erroneous attenuation correction. This study, together with the first phase of phantom measurements, confirmes that the transmission source activity influences strongly the quantitative reliability of PET images, but also that the transmission scan length can be shortened to a minimum as result of an optimally planned measurement schedule. The ability of PE T to determine the spatial distribution of activity concentration in vivo is mostly due to the possibility to do an exact attenuation correction. The accuracy of this correction influences strongly the accuracy of quantitation, because typically the correction factors are in the range of 500-2000 %. As the correction is based on a transmission scan, in theory complex object geometries with nonhomogeneous attenuation coefficients can be treated. Practically, however, there are problems mainly due to the limited statistics of the transmission scan. This is especially true for modem scanners with high transverse and axial resolution and therefore fine spatial sampling. So a single correction factor typically is based only on 40 counts for brain-and 0.5-30 counts for abdominal imaging. Without any processing the associated noise completely destroys the emission image. By smoothing the transmission data this effect can be reduced, but the transmission spatial resolution is degraded from 6 mm tol2 mm. So at the borders between changing attenuation coefficients systematic errors are introduced. So contrast for a cold, airfilled sphere is reduced from 70 % to 65 % (40 mm in dia.) or from 30 % to 17 % (15 mm dia.), respectively. Using realistic phantom setups with different attenuation coefficients simulating tissue, lung, and bone the problems of attenuation correction, dependent on the degree of smoothing (2-or 3-dimensional, repeated application), are demonstrated. The data are compared to the results of an analytical correction assuming constant ~t, which introduces unacceptable errors (e.g. changes image activity concentration from cold to hot) for these complex geometries. In addition the degradations caused eventually by external absorbers (patient table, head holder) are discussed. The problems shown are common to all linear correction methods and demonstrate the need for more sophisticated non-linear correction methods. other g e n e r a l expenses and financial burdens, the running cost of a PET center -based on obsolescence of 5 years for the tomograph and I0 years for the rest of equipment -was in 1991 1.048.000 ECU. The financial burdens due to investment with an annual interest rate of 7% were in the same year 132.500 ECU. With this rate of interest, the cost of i n v e s t m e n t ( d e p r e c i a t i o n and interests) was about 46% of the total cost. Considering running costs as fixed, except for the disposables, the average cost per study was between 1.500 ECU (800 annual studies) and 1.980 ECU (600 annual studies). These results force a careful evaluation relatively to the acquisition of PET technology from health ca~e structures specially considering the potential demand of studies. E. Voth, A.R. B6rner, P. Theissen, H. Schicha Dept. of Nuclear Medicine, University of Cologne, Cologne, Germany In 30 patients with Graves disease admitted for therapy with 131-1, 18-FDG positron emission tomography (PET) was performed. 99m-Tc scintigraphy, sonography, 131-1 uptake and t-r3, fT4 and TSH were available. 18-FDG PET was performed in all 30 patients before 131-1 therapy. Following determination of blood glucose level, 370 MBq of 18-FDG were administered intravenously to the fasting patient. Using a CTI ECAT ECACT 921 (16.2 cm axial field of view, 47 planes), transmission (30 min) and emission scans (8x5 min) were performed. Reconstructed data were interpolated in 3-D technique. For quantitative analysis, four coronal 5ram slices were added and thyroid FDG-uptake (% / ml thyroid tissue) was determined using ROI-technique. There was marked thyroid 18-FDG uptake in all patients, increasing with activity of hyperthyroidism and decreasing with age. Patients with high 18-FDG uptake showed a short biological half-life of 131-1 under therapy conditions. Using multiple regression analysis, significant relations of 18-FDG uptake were determined to biological half-life of 131-1 under therapy conditions (partial correlation coefficient m-0.44, p=0.01), to amount of antithyroidal medication (r=0.35, p=0.04) and to patient's age (m-0.33, p=0.04). Combination of these three relations resulted in a total correlation coefficient of R=0.72 (p=0.001). The correlation of thyroid 18-FDG uptake to the biological half-life of 131-1 and to the amount of antithyroidal drugs might be explained by activation of glucose dependent transmembrane transporter proteins (P-Glycoprotein), the product of the multidrug resistance genes (MDR1 and MDR 2). Induction of P-glycoprotein and other energy dependent membrane transporters may be the cause of both increased FDG-uptake and short biological half-life of 131-1. Because of the unwanted effects of TSH stimulation test, recently TI-201 has been proposed for the visualization of supressed thyroid tissue in patients with autonomously functioning thyroid nodules (AFTN). It is suggested that TSH control is not a major determinant of T1-201 uptake. More recently, Tc-99m MIBI has also been recommended to be used for the same purpose. However, the mechanism of thyroid uptake of Tc-99m M]]3I is contraversial. In this study, we tried to find out the ideal agent in the visualization of supressed thyroid tissue in patients with AFTN. Fourteen patients (12F,2M) with toxic solitary AFTN visualized on Tc-99m pertechnetate scan were included in this study. 15 rain. images were obtained at~er IV injection of 80-100 MBq of TI-201 and 350-400 MBq of Tc-99m MIBI with 3 days interval. The scintigrams were analysed both visually and semiquantitatively. For the semiquantitative analysis, ROIs were set over AFTN and contralateral normal thyroid tissue and the average counts in every ROIs were determined. After background correction, by dividing nodular counts to normal tissue counts, nodule / extranodular tissue ratios were calculated.The mean tissue ratios for pertechnetate, Tc-99m MIBI and TI-20lwere found to be 10.04±4.18,4.45±2.03, 1.75±0.19 respectively. Our results showed that TI-201 uptake of supressed thyroid tissue was more prominent and statistically significant (p<0.05) than that of Tc-99m MIBI in toxic AFTN. This might be due to the higher metabolism and / or TSH dependent uptake of Tc-99m MIBI. In conclusion, TI-201 is superior to Tc-99m MIBI in the visualization of supressed thyroid tissue in patients with AFTN even its poor physical characteristics. Toxic adenomas are rarefying in Berne From a total of 12'320 patients referred for thyroid scintigraphy to our nuclear medicine department during the years 1976, 1982 and 1991, 1'125 (9.1%) were clinically or latent hyperthyroid. The frequency of immunogenic versus non-immunogenic hyperthyroidism (IH versus NIH) and of toxic adenomas (TA) versus multifocal functional autonomy (MFA) were evaluated in these patients. 413 Results: 50 years after the beginning of a progressive iodine supplementation via kitchen salt in Switzerland, NIH is still the most frequent form of hyperthyroidism in Berne. Over the 18 year period evaluated, the IH proportion remained constant. Within a constant share of 60% of NIH, the TA/MFA ratio dropped from 2.4 (1976) over 0.9 (1982) to 0.4 (1991 ) . A decreasing proportion of TA and a rising MFA frequency could be markers of the progressively diminishing iodine deficiency. Indeed, the urinary excretion of iodine, from 30 pg/g creatinine in 1920, had risen (1981) (1982) (1983) (1984) (1985) (1986) (1987) (1988) (1989) (1990) ) to a level above 100 pg/g creatinine (WHO standard), to drop again, in 1992, to a 87-+36 pg/g creatinine level. A rising proportion of TA seems to be a marker of an increasing or newly installed iodine deficiency, as has recently been observed in several parts of the European continent. Thus, the epidemiology of hyperthyroidism is in continuous change in a prealpine country. The previously available imaging procedures -CT and MRI -have been used routinely in cases of endocrine orbitopathy (EO) to characterise morphological aspects of the retrobulbar space. These methods, however, do not provide information related to functional aspects. The capability of the somatostatin analogon Octreotide to localize activated lymphocytes in inflamatory lesions provides investigators with a new tool for this task. The aim of this study was to compare the clinical findings with both MRI and Octreoscan in cases of EO. A series of 11 patients with Graves' disease were included in the study. The ophthalmological score was determined according to Mourits' scale. Both eye muscle thickening and eye muscle oedema were taken as parameters of the MRI investigation. For the Octreoscan studies 111MBq 111-In-Octreotide were injected i.v., planar and SPECT images were taken 2 hours p.i. A study was called positive if tracer accumulation was documented in at least two corresponding slices after SPECT reconstruction of the orbital region. A higher rate of positive findings was seen with the Octreoscan (88%). On the other hand, muscle thickening was apparent in 66% and oedema only in 55°/'0 of the cases. The opthalmological score correlated well with the Octreoscan results. In this preliminary evaluation, retroorbital changes seem to be more apparent in the Octreoscan as compared to MRI imaging. The underlying pathogenetical mechanism reason for this could be the presence of activated lymphocytes. Development of cholestasis after orthotopic liver transplantation (OLT) in children may be related to various causes, i.e. graft rejection, hepatitis, or segmental biliary stenosis (BS). This latter complication may be suspected by ultrasound (US) when bile ducts are dilated. Since functional biliary alterations may precede morphological alterations, we have now evaluated the usefulness of hepatobiliary scintigraphy in the early detection orBS when US is still normal. We have reviewed 131 consecutive scans performed in 85 post-OLT children with cholestasis and normal US, including 14 patients (18 studies) with proven BS and 71 patients (113 studies) without stenosis (NBS). Bile ducts activity was visually graded G1 (no or faint bile ducts visualization during less than 60 min) or G2 (bile ducts visualization exceeding 60 min with or without tracer pooling). Hepatic and bile ducts time/activity curves were generated in order to obtain quantitative parameters of biliary activity and clearance. The diagnosis of BS was confirmed in 4 of the 108 G1 studies and in 14 of the 23 G2 studies, indicating for the visual method a sensitivity of 78%, a specificity of 96%, a negative predictive value of 96% and a positive predictive value of 6 I%. Although the mean quantitative parameters were different in patients with and without biliary stenosis and correlated with visual grading, all values observed in BS were in the range of those observed in NBS. Conclusion: 1.visual grading of the biliary activity is effective in the early detection ofbiliary stenosis in post-OLT children, 2. quantitative data analysis does not improve the accuracy of the method. Not only the skeletal muscle but also the myocardium is one of the target organs of thyroid hormones. In 15 hypothyroid (TSH > 30 gIE/mI) patients with thyroid carcinoma after thyreoidectomy and radio iodine therapie, additionally phosphorous-31 nuclear magnetic resonance spectroscopy (P-MRS) was performed before iodine-131 -whole-body-scintigraphy. It was assessed, whether alterations of the myocardial phosphate metabolism occur with hypothyroidism similar as in skeletal muscle. For comparison it was proved, whether left ventricular function of these patients is decreased at rest. In patients and 15 healthy volunteers P-MRS (volume selection method ISIS at the anterior, lateral, and septal left ventricular wall; EKG-triggering, repetition time = 3 s; average of 512 endsystolic measurements) and magnetic resonance imaging (dynamic mid-ventricular transverse and sagittal oblique gradientecho (GE) scans) were applied. The ratio of the peak-areas of phosphocreatine (PCr) and B-ATP has been designed as parameter for the status of the myocardial phosphate metabolism. Values were corrected for partial saturation and contamination with blood. Left ventricular function has been evaluated quantitatively measuring the ejection fraction (EF) by the area length method on the GE-scans. In comparison to the normal subjects with a PCr/g-ATP-ratio of 1.79 _+ 0.21, this ratio and, therefore, first of all the PCr of the patients with 1.23 + 0.32 was significantly decreased (p = 0.005). Besides the decrease of PCr, only 5 of the 15 patients showed a diminished left ventricle function at rest with EF values below 50 %. Left ventricnlar dilatation or myocardial thinning was not observed. This results emphasize that hypothyroidism affects the phosphate metabolism of the myocardium. The drop of PCr was unexpectedly marked. By this means, at least at rest no high grade reduction of left ventricuIar function was caused. Presently, the consistency of the existing results is proved by enlargment of the patient group and control examinations at euthyroidism. Chronic liver disease is a main complication of Cystic Fibrosis, and it has been recognized as a risk factor for early death. Aim of the present study is to evaluate the hepatobiliary function by the aid of trimethyl-Br-IDA-99m-Tc (TMBIDA) scan, in 48 children with Cystic Fibrosis and clinical or US signs of known or suspected associated liver disease. Four groups of pts were evaluable: 20 with liver cirrhosis (LC), 13 with not cirrhotic-liver involvement, 15 with no liver involvement (8 with biliary sludge and 7 with meconium ileus). In 29 pts, the scan was repeated 11-36 months after therapy with Ursodeoxicholic acid (UDCA), with a total of 87 scintigraphy. Morphological abnormalities, hepatic extraction fraction (HEF) and time of visualization of intestine (TI) were evaluated after i.v. inj. of 111-185 MBq of TMBIDA. Parenchymal abnormalities and bile ducts dilatation were observed in 27/48 pts (56%) with a slight difference when comparing LC vs the other groups (70% vs 46%). HEF and TI were slightly prolonged in pts with LC (30.2 and 28.3 min, respectively) and in pts with elevation of liver function tests (28.8 and 28 rain), in comparison with all the other pts, irrespectively to the clinical group. Both morphological and functional parameters improved, according with the clinical status, after UDCA therapy in all but 2 LC pts. In conclusion our data demonstrated that scintigraphy well correlates with clinical status and it is a good parameter of treatment responsivity. Moreover it allows to identify liver abnormalities in 2/3 ofpts without signs of liver disease. The biliary reflux was seen in 14 children (44 Z), the results were vague in 6 (18 %), the test was negative in 12 (38 %). Reflux index was 3.4 +/-1.1%. Control scintigraphy was performed i n 8 children after the treatment with cisapride and revealed the withdrawal of the reflux in T, with persistence in i. This was in accordance with clinical symptoms. Those results arm in accordance with the results For 10 years MIBG has been used successfully in the diagnosis and staging of children with neuroblastoma. Because 1-131-MIBG allows delayed imaging, it is reported to have a higher sensitivity than 1-123-MIBG. To study the sensitivity of 1-123-MIBG we evaluated all MIBG scans performed between 1984 and 1992 in 91 children suspicious for neuroblastoma using I-123-MIBG exclusively. 50 males and 41 females were studied. The age of the children varied between 4 weeks and 18 years (average age: 33 months). The results of MIBG scans were compared to those of other imaging techniques (ultrasound, X-ray, MRI, CT, bone scan), of catecholamine levels in urine and plasma, of Neuron Specific Enolase (NSE) levels in plasma, and of bone marrow histology/cytology. Neuroblastoraa was confirmed histologically in 81/91 children and excluded in 10 children. The primary tumor was localized in the abdomen in 60, in the chest in 18, in the neck in 2, and in one case in the pelvis. 48 of the children were in stage IV, 19 stage III, 9 stage I or II, and 5 were in stage IVS. 55 out of 81 children had metastases: 12 bone marrow, 4 bone, 25 both bone marrow and bone involvement. 26 children had soft tissue metastases (8 liver, 4 intracerebral, 2 scrotal and 12 lymph node). Comparing the MIBG results with those of all other methods combined, primary tumors were true positive (TP) in 76 cases, in 10 cases true negative (TN), and in 5 cases false negative (FN). Bone marrow involvement or bone metastases could be diagnosed in 40/41 cases; 50/50 studies were TN. Soft tissue metastases were TP in 22 cases, and FN in 4 cases (2 liver and 2 lymph node metastases). No false positive I-123-MIBG scan was observed in the entire study. With a sensitivity of 94% for primary tumor, 98% for bone/bone marrow involvement, and 85% for soft tissue metastases without false positives I-123-MIBG results compares favorably with published data for 1-131-MIBG. Despite the shorter imaging sequence 1-123-MIBG seems to be an equally reliable tool in diagnosis and staging of children with neuroblastoma. Hypoproteinemia is a pathological process with many possible etiologies. Occasionally, the source of protein loss is difficult to pinpoint. We have evaluated the applicability of 99m Tc-albumin scintigraphy for the detection of gastrointestinal protein loss. Eleven children, five females and six males (ages eight months to 19 years) were scanned dynamically for one hour post injection. Static images were obtained at 2,4, and 6 hours. All patients had documented total serum proteins and albumins significantly below normal. Most patients had fecal l-anti-trypsin performed for correlation. Three liver disease patients with a low likelihood of GI protein loss were normal (controls) as demonstrated by no WmTc-HSA activity within any ~rtion of the bowel. Eight patients demonstrated Tc-HSA activity within the bowel and the site of leakage could be determined to assist surgical planning. In these patients, 9~mTC-HSA activity in the bowel correlated with elevated fecal l-anti-trypsin levels. We believe this is the largest series to date demonstrating that the use of ~TC-Albumin in detection of GI protein loss offers the following advantages: I) High sensitivity; 2) Ability to localize accurately the site of leakage, and therefore be useful in surgically correctable disease; 3) Reasonable cost. 13 children with advanced NBL received ~3:I_MIBG as therapy. They were either refractary to conventional therapy or showed disease relapse after initial successful treatment, in one patient the MIBG was given as a consolidation therapy. II children were on stage IV and 2 on stage Ill. Chosen criteria were: positive I~+I-MIBG in all tumoral lesions and no bone marrow involvement. Many of the patients had received previous intensive therapy, so depression of pre-treatment blood cell count has been in cases a limiting factor for treatment. A total of 59 MIBG courses were administered by infusion. In most children the dose was divided into two portions each infused over a period of 4 hours with a 24 hr, interval between them. Courses were repeated up to 4 times and the maximum activity given to one patient has been 22.200 MBq. Main toxic elect was thrombocytopenia. Antitumoral effects were evaluated: there was I complete remission; 4 minor or subjective response and 8 no response (no changes or disease progression). Children suffering from bone pain became free of complaints during the first three days after treatment. These data suggest that greater effort should be placed to identify the conditions in which NBL may have a real benefit from MIBG therapy in comparision with more standardized treatment schedules, In order to evaluate the significance of dobutamine stress testing, gradient echo magnetic resonance imaging (MRI) and 99m-Tc methoxy-isobutyl-isonitdle (MIBI) SPECT were performed in 32 patients at rest and during dobutamine stress. All patients had at least one coronary artery stenosis of >-50%. Dobutamine stress test (5, 10, 15, 20 pg/kg /min.) was performed during MRI image acquisition with simultaneous MIBI-injection at the maximum dobutamine dose. Segmental MIBI-uptake and wall motion were evaluated quantitatively on corresponding short axis and transverse tomograms. MIBI-SPECT and MRI were considered pathologic if dobutamine induced perfusion or wall motion abnormalities occurred in at least two neighboudng segments. For comparison with coronary angiogrephy segmental MIBI-SPECT and MRI findings were compared to the respective coronary artery perfusion territories. Dobutamine induced perfusion and wall motion abnormalities were detected in 28/32 (87%) and 27/32 (84%) patients, respectively. After reperfusion of severely ischemic myocardium, prolonged myocardial dysfunction may occur in the salvaged area ("stunning"}. This is thought to be caused by Calcium (ca) overload. Co-55 can be used to image Calcium. Co-55 has already been used to visualize ischemic brain damage. To investigate the possibility of Co-55 as a Ca tracer and therefore image myocardium at risk, 2 mCi Co-55 was administered i.v. to 2 healthy volunteers and 2 patients with an evolving acute myocardial infarction before reperfusion with balloon dilatation. Co-55 PET was performed approximately 24 hours post injection. In healthy volunteers there is hardly any myocardial Co-55 uptake. The patients clearly show highly selective uptake of Co-55 in the ischemic border region. This indicates Ca overload due to reperfusion in these regions, demarcating the area of stunned myocardium. In conclusion, Co-55 PET visualizing stunned myocardial tissue after reperfusion, may become a promising new method for early detection of ischemic and salvaged myocardium and for monitoring the effect of therapeutic interventions (Ca-antagonist) in these situations. Besides being a relatively inexpensive PET radiopharmaceutical, imaging with Co-55 can be delayed 24 hours after the acute ischemic event, making it a convenient tool for aiding patient selection for a more aggressive anti-ischemic treatment, determining early prognosis and therapy evaluation. To estimate the disagreement between stress (ST)-redistribution (RD) mid reinjection (RI) imaging, 12 experienced Nucl. Med. Depts. enrolled 402 patients with at least one ST perfusion defect. To eliminate external sources of variability the same type of gamma camera, acquisition protocol and computer software was used for three views planar imaging of a conventional 3-4 hour ST/RD study. A new set of images was acquired 30 min after T1-201 RI performed ha the same day (Group A, n=230) or in a different day (Group B, n=i72) from to the ST/RD study. Four hour delayed imaging after RI was repeated in Group B only. The left ventricle was divided into 13 segments and blindly evaluated, in a core center, by 3 independent observers, according to a 5-pohat scale (0 =normal, 4=no uptake). Reversibility was defined as a shift towards normal of -> 1 grade on subsequent images. Of the 5195 evaluable segments, 2058 (40%) had ST perfusion defects, of which 566 (27%) were severe irreversible defects (SID: score 3-4). After RD, 1313 (64%) defects remained totally irreversible (TID) and 415 of them (32%) were SID. After RI the number of TID decreased to 1033 (50%), 341 (33%) of which were SID. When comparhag RI with RD imaging 403 (31%) out of the 1313 TID and 105 (25%) out of the 415 SID at RD improved after T1-201 RI. The change in segmental uptake was of only one degree on the scoring scale ha 91% of segments evaluated after RI. In Group B the agreement in die segmental scoring of TI-201 perfusion defects, at early and delayed imaging after RI, was excellent (Kw = 0.947). ha conclusion the improvment in TI-201 activity after RI of apparently irreversible defects after conventional ST/RD study is reproducible also when a strictly controlled methodology of image acquisition and analysis is adopted. In a large and unselected population of ischemic pts, the segmental prevalence of this phenomenon is less than previously repoll.ed. No significant differences were found when comparing early mad delayed imaging after RI. * SIRT: Italian Multicentre Study on Thallium Reinjecfion. The protective role of collateral blood flow on myocardium sustended by stenosed coronary arteries has long been recognized. Its role on the diagnostic performance of dipyridamole stress test has not been established. 26 patients with well-developed intercoronary collaterals and 12 control pts without collaterals were studied at rest and after dipyridamole infusion (0.84 mg/kg). The regional myocardial activity of SESTAMIBI was measured with SPECT using a 5-point scoring system and 13 segments. The severity of coronary stenoses (Gensini score) was similar in both groups: 12.7+7.1 vs 11.3+6.9 (p= NS). Clinical and ECG evidence of acute myocardial ischemia were noted during the test in 15 pts with collaterals and in 2 pts without collaterals (p= 0.004). Dipyridamole-induced perfusion changes were observed in 24 pts: 9/20 pts (45%) with ECG Q-wave vs 15/18 pts (83%) without ECG Q-wave (p= 0.02). There was a significant association between perfusion changes and the presence of collaterals in pts without ECG Q-wave: 13/13 pts with collaterals vs 2/5 pts without collaterals showed dipyridamoleinduced changes (p= 0.01). Of the 76 diseased vessels (> 70% luminal narrowing), 64 vessels supplied territories containing at least 75% of myocardium with residual SESTAMIBI activity at rest. Dipyridamoleinduced perfusion changes were observed in 40/64 territories (63%). A significant association was found between perfusion changes and the presence of collaterals: 18/21 vessels with collaterals (86%) vs 22/43 vessels without collaterals (51%) showed perfusion changes (p= 0.006). The mean difference between stress and rest peffusion scores was higher for collateralized vessels than for non-collateralized vessels (3.6+3.4 vs 2.0+3.1; p= 0.065). These findings suggest (1) that collateral vessels supplying stenotic coronary arteries are associated with ischemia observed in some patients in response to coronary arteriolar vasodilatation (coronary steal effect); (2) that collateral vessels play an important role in the diagnostic performance of dipyridamole stress test in patients without ECG Q-wave. Dipyridamole-induced perfusion changes were observed in all pts with angiographic collaterals but in only 40% of pts with similar CAD severity but without collaterals. Tetrofosmin (Tetro) is a new Tc99m labeled myocardial perfusion agent. Biodistribution studies indicate more attractive heart-to-adjacent organ biokinetics than for Tc99m Sestamibi (Mibi) after injection during exercise. To determine whether Tetro could also be more suitable than Mibi for Dipyridamole stress test (Dipy) in a one-day imaging protocol, we compared the distribution of these 2 tracers in patients with proven or suspected coronary artery disease. Six to 9 mCi of Tc99m Tetro were injected at rest and 23-28 mCi were injected 4 hours later, during Dipy infusion (0.84 mg/kg). Planar and myocardial SPECT images (MultiSPECT3, High Res collimator, 128 matrix) were obtained 60 minutes after the rest injection, and 30 min and 60 rain after Dipy injection. The Mibi study was obtained using exactly the same protocol, either 48 hours before or after the Tetro study. So far, 12 patients have completed the study. High quality SPECT images with good myocardial delineation and adequate contrast between the heart and background were obtained with the 2 tracers, as well after rest as after Dipy injection. Mean + sd myocardial count rate were 5.4+1.9 and 5.8+1.8 counts/pixel/min/mCi for Tetro and for Mibi, respectively (p= NS). Tetro and Mibi heart/lung ratios averaged 3.1_+0.7 and 3.2_+0.5 after rest injection (p=NS) and 3.5_+0.6 and 3.6_+0.5 after Dipy injection (p=NS). The heart/liver ratio was similar for both tracers 60 minutes after rest injection (1.4+0.4 versus 1.2+0.6; p= NS). The Tetro heart/liver ratio was 0.78+0.09 at 30 rain after Dipy injection and increased tol.6_+0.2 at 60 minutes. At this time, the Tetro heart/liver ratio was higher than the Mibi heart/liver ratio (1.2_+0.5; p< 0.01). We conclude that Tetrofosrnin offers modest biokinetic advantages in comparison with Mibi for Dipyridamole stress test performed with a one-day imaging protocol. Immunoscintigraphy using Tc-99m labelled monoclonal antibodies (Mab) today represents a widely used method in the detection of tumors. However, induction of HAMA after multiple administrations or even after a single injection limits the usefulness of this approach in the follow-up of cancer patients. This study presents the first immunoscintigraphic results after the injection of the totally human Mab Tc-99m-88BV59 (OncoSpect TM, AZKO--Organon Teknika bv, Turnhout, Belgium) in patients with a history of colorectal cancer. Mab 88BV59 (IgG Kappa 3 subclass, 170 KD) is a panadenocarcinoma antibody which detects a cytokeratin-like antigen and has been shown to react with >90% of primary colorectal cancers as well as with recurrences and metastases. ISC (8 anterior/posterior planar images as well as SPECT of the abdomen and pelvis) was performed 18 to 20 hrs after injection of 1.1 GBq (30 mCi) Tc-99m-88BV59 (9.46 mg). The scintigraphic results were compared to CT scan and sonography; all patients subsequently underwent surgery thus allowing to evaluate the immunoscintigraphic findings histologically. There were no adverse effects and no human anti-human (HAHA) responses. Labelling efficacy reached from 97 to 99.9%. The detection rate was 2/2 for primary tumors, 6/7 for liver metastases, 2/2 for lymph node involvement, and 2/2 for recurrences. All lesions detected scintigraphically were confirmed by histology (no false positive findings). In conclusion, this first totally human Mab proved useful in the detection of colorectal primary tumors, recurrences and lymph node metastases providing the advantage of no induction of HAMA and thus allowing repeated studies in the follow-up of patients suffering from colorectal cancer. Tetrofosmin is a new technetium labelled lipophilic cation evaluated for use as a myocardial perfusion tracer. Same day stress/rest planar and tomographic images obtained as part of the phase III clinical trial were compared to planar thallium and to angiography in 72 patients with definite or suspected coronary artery disease. Studies were processed on a common computer and read separately by four investigators unaware of patients identification. 42 patients had previous and 30 no previous myocardial infarction. 38 patients had multiple vessel disease (lesions _> 50%) and a total of 111 arteries had stenosis. Spect tetrofosmin was normal in 8 of the 9 patients without significant coronary lesion, thallium planar and tetrofosmin planar images were normal in 7 of these 9 patients. 12 of 13 patients with previous myocardial infarction and single (10) or no (3) residual vessel lesion had tetrofosmin Spect abnormalities versus 9 with planar thallium and 8 with planar tetrofosmin. 26 of 29 patients with multiple vessel disease and previous myocardial infarction had fixed defects (11 patients) or partially reversible defects (15 patients) as compared to 9 and 13 respectively with planar tetrofosmin and to 7 and 16 respectively with planar thallium. Finally Spect tetrofosmin demonstrated stress abnormalities in 17 of 21 patients without myocardial infarction as compared with 14 using planar tetrofosmin and 13 using planar thallium. Overall, Spect tetrofosmin recognized disease in 69 arterial territories versus 59 for planar tetrofosmin and 58 for thallium. We conclude that the use of Spect plays a major role in the improved sensitivity and specificity demonstrable using Tc-99m tetrofosmin. The aim of this study was to compare diagnostic accuracy and kinetics of two 99mTc-labeled monoclonal anti-CEA antibodies (MAbs) (complete versus fragmented) in colorectal cancer patients intraindividually. 22 patients were investigated with both MAbs within one week: 740-1295 MBq of the complete IgG1 MAb BW431/26 (1.5 mg of protein; Behringwerke FRG) and of the F(ab')2/Fab" fragment mixture F023C5 (0.35 rag; Sorin Biomedica, Saluggia, Italy) were injected intravenously. Planar and whole body scans were performed 1, 4, 24 and in special cases 48 h p.i., SPECT after 4 and 24 hours. The following localizations could be visualized (F023C5-posJBW431-pos./all lesions): Primary tumors 2/1/2, locoregional recurrences 10/8/10, liver metastases 12/10/14, kidney met. 0/1/1, lung met. 0/1/1, lymph node met. 6/5/6, bone met. 2/2/2, brain met. 2/2/3, peritoneal carcinoses 4/3/4. SPECT was superior to planar scans in 35%, especially in locoregional recurrence, liver, kidney and lung met. With MAb fragments, tumor detection was possible in 17% after lh, in 94% after 4h, whereas with complete MAb, in 48% 24h or even 48h scans were necessary. The tumor/background ratio of liver metastases was significantly lower with fragments, compared to complete MAb (1.24+0.10 vs. 1.67-+0.32; p<0.01). In conclusion, with fragments (due to faster whole body clearance), tumor detection is possible with higher sensitivity earlier p.i. in comparison to whole IgG1. Therefore, for Tclabeling with its short physical half-life, fragments seem to be more suitable. The lower tumor / background ratio of liver metastases results probably from the lower antigen affinity known for fragments, despite their higher sensitivity. A. Akamune, Y. Kimura, S. Nakamura, T. Tsuda, T. Fujii, M. Kawamura, S. Tanada and K. Hamamoto. Dept. of Radiology, Ehime University Shool of Medicine, Shigenobu-cho, Onsen-gun, Ehime, Japan CLONAL ANTIBODY IN RADIOIMMUNOSCINTIGRAPHY Significant non-specific accumulation of rain-labeled diethylenetriaminepentaacetic acid-monoclonal antibody (mln-DTPA-MoAb) into normal tissues such as liver and kidney makes it difficult to detect the malignancies in the abdomen. We have so far shown that DTPA could reduce rain accumulation to liver in animal model. This in vitro and in vivo sudies were performed to evaluate the effect of asialoglycoprotein receptor (ASGPR) on the surface of hepatocyte on the accumulation of mln-DTPA-MoAb to liver. In vitro studies : The uptake of mln-DTPA-MoAb by isolated rat hepatocytes was suppressed by adding MoAb itself, human IgG, galactosyl human serum albumin (GSA) and GSA-DTPA which were proportional to their concentrations, mln-DTPA-MoAb uptake was much more suppressed by GSA-DTPA than by GSA alone. The hepatocyte uptake of 125I-GSA-DTPA was higher than that of ~251-GSA. MoAb which is glycoprotein, was considered to be uptaken in part by hepatocytes through ASGPR. In vivo studies : Biodistribution and imaging studies with mln-DTPA-MoAb depicted that the administration of cold GSA-DTPA reduced the undesirable uptake of mln-DTPA-MoAb by the liver and kidney both in normal and tumor-bearing mice. These results show the usefulness of administration of cold GSA-DTPA in mln-DTPA-MoAb scintigraphy. . Liver metastases were confirmed in 9 patients, IS revealed "hot spots" in 6 and unspecific "cold lesions" in 3 of them. PET-scans of the liver were available for 11 patients (7 true+, 4 true-, among them 2 hemangiomas with doubtful findings of IS). All lymphnode metastases were identified by PET, 3 out of 5 by IS. Local recurreneies (n=6) were correctly localized by both procedures. In 2 patients with a history of radiotherapy because of rectal cancer, PET yielded false positive findings within the portal while IS was normal. The results indicate that PET is superior in diagnosing liver or lymplmode metastases, which might be attributed to better spatial resolution of PET-scanners and higher tumor/non-tumor ratios of FDG. IS proved to be more specific in case of previous irradiation (no false positives) and is the method of choice in case of unknown tumor location (screening by use of whole body scanning). The biodistribution of mIn-pentetreotide (rain-P) was measured m vivo in 44 patients with suspicion of GEPnt. Patient preparation included administration of laxatives and withdrawal of octreotide therapy. Patients were imaged 4 and 24h after injection of-200MBq m In-P. Organ and tumor activity was determined using the geometric mean method and expressed as % injected dose (%ID) or by quantitative SPECT and expressed as %ID/100ml. The diagnosis of GEPnt was proven in 36 patients and mIn-P was positive in 31 cases and negative in 13. Total liver (L) and spleen (S) activity was similar at 4h (L:3.7+1.2, S:2.8+1.6%ID) and 24h (L:4.0_+1.7, S:3.0_+1.8%ID). Kidneys (K) activity decreased from 5.9+2.5%ID at 4h to 5.1+1.8 at 24h (p<.001) and a mean decrease of 62% was measured over background areas. At 24h, the activity expressed as %ID/I00ml was 4-fold lower in L (0.2+0.1) compared to S (0.8__+0.5) or K (0.8+0.4). No differences in L, S or K uptake were observed in patients with positive or negative scans. At 24h, the thyroid was visualized in 92% of patients (0.02+0.02%ID), the pituitary in 74%, gallbladder in 14% and breast in 18% of females. Bowel activity was se~n in 19% of patients at 4h and 91% at 24h. The tumor activity was similar at 4h (0.01 to 20%ID; median 0.28;n=50) and 24h (0.02 to 18%ID; median 0.31). At 24h, the median tumor uptake was 0.81%ID/100ml with a median tumor/liver ratio of 3.8 (range: 0.8-29.3, n=59) . Conclusions: I) with the exception of kidneys, the tumor and organ uptake of mIn-P remains stable between 4 and 24h, 2) in GEPnt patients, mIn-P provides a high target-to-nontarget ratio. In a prospective longitudinal study of 197 cases of dementia (mean age 73.2 range 39-95) and 114 controls (mean age 70 range 34-94) annual medial temporal lobe (MTL) oriented X-ray CT and Tc-99M HMPAO SPET scans are used to evaluate the diagnostic and prognostic potential of structural and functional neuroimaging in the differential diagnosis of dementia. Some subjects have bad seven annual evaluations. So far of 90 who have died, 87 have come to post mortem (PM)(97%). 52 had more than 1 annual scan (lx6, 5x4, 19x3, 27x2) . Histology is known for 77:52 had AD (27 >1 annual scan), 17 had other dementias (12 >1 annual scan) and 8 controls had no CNS pathology (7 > 1 annual scan). The combination of MTL atrophy and parietotemporal (PT) hypoperfusion on SPET is thought to predict AD. We assessd scans for significant MTL atrophy (<0.79 multiples of median for age), PT hypoperfusion, and the combination of both, at intervals before PM and up to 28/2/94 in the living controls (see table) . Both criteria have been positive at least 56 months before death in confirmed AD, are much less common in other dementias and virtually absent in controls. 48-60+ 2/3 2/3 2/3 0/1 0/1 0/1 2/18 0/19 0/19 The rate of MTL atrophy in AD (1.89mm/yr,95%CI 1.25-2.54) is an order of magnitude greater than controls (0.21mm/yr,95%CI 0.02-0.39) and correlates directly with cognitive decline. Such dramatic MTL atrophy suggests that AD is a disease rather than the inevitable consequence of ageing. These findings have important aetiologie, diagnostic and therapeutic implications. The validity of clinical testing is not possible in all patients with PA, due to frequent difficulties in applying neuropsychometric tests. Structural neuroimaging can be normal or show typically left perisylvian atrophy in some patients. The aim of our study was to evaluate the usefulness of HMPAO,SPECT as a diagnostic tool in PA, in comparison with MR/and clinical follow-up. HMPAO brain SPECT was performed on I 1 patients (10F, mean age 68_+8 yrs) with a mean of 4 yrs of language dysfunction (range 2-15 yrs). All patients underwent a MR/ study. Criteria of inclusion were: 1) a history of unexplained progressive language disturbance and 2) the absence of other cognitive impairment for at least 2 yrs after the onset of aphasia. During a 8-33 months follow-up, 5 patients were re-examined by SPECT (4 once and 1 twice). The presence of atrophy (MR/) and hypoperfusion (SPECT) were graded as absent (a), mild (ml), moderate (md) or severe (s). All the SPECT and MR[ abnormalities were located in the left hemisphere. Perfusion defects were found in the posterior temporal region (PT) in 11/11 patients (5ml, 3md, 3s), in the anterior temporal region (AT) in 10/11 (9ml, lmd) and in the frontal lobe (F) in 3/11 (3ml) . MR[ showed atrophy in the PT in 8/11 patients (6ml, lmd,ls), in the AT in 6/11 (4ml, 2md) and in the F in 2/11 (lml,lmd). In agreement with clinical deterioration, follow-up SPECTs showed impairment in 5/5 patients. No relationship between perfusion defects and atrophy was found (Fisher's exact test N.S.) Patients with PA show temporal perfusion defects, mainly in the posterior region, including Wernicke's area. HMPAO-SPECT shows a higher number of severe abnormalities than MR/, and may demonstrate functional impairment in PA patients with normal MRI. EA van Roven, WA van Gool, GJM Walstra, S Teunisse, F van der Zandt, HC Weinstein. Dept. of Nuclear Medicine and Neurology, Academic Medical Centre, Amsterdam, Netherlands. Based on the observation of bilateral temporopariatal hypoperfusion in Alzheimer's disease (AD), cerebral blood flow SPECT has been advocated as a powerful diagnostic tool in the evaluation of demented patients. We assessed if routine SPECT in eldedy, mildly demented outpatients increases the a priori diagnostic sensitivity and specificity of a careful clinical and neuropsychologic examination alone. A total of 110 consecutive patients, referred by general physicians for memory disorders, were studied. SPECT images wens acquired on a multidetector brain SPECT system (SME810) after the injection of 550 Mbq s~=-I'c HMPAO. A diagnosis of probable AD (McKhann criteria) was made in 68 patients (mean age 79.3 yr) based on clinical examination, neuropsychologic tests (CAMDEX-N), ancillary investigations and a 6 month follow-up. Temporopariatal (TP) perfusion, quantified as the ratio of the activity in the cerebellum was significantly lower in AD patients than in non-demented age matched controls. ROC analysis revealed a cut-off level of 0.79 for the TP ratio to be most favourable. Using that value the specificity was 89% and the sensitivity only 43% for detecting probable AD. SPECT imaging proved to have contributed to the final diagnosis in only 8% of the demented patients investigated. We conclude that in this large series of patients, routine cerebral blood flow SPECT does not contribute substantially to diagnostic accuracy after clinical examination using current diagnostic criteria. TO investigate the effect of i.v. diazepam on rCBF at rest and following activation, 99mTc-EMPAO/SPECT study was performed in 12 healthy right-handed volunteers (mean age= 23±1.3 yrs). Baseline anxiety levels were rated by State-Trait Anxiety Inventory (mean:41.7±5). For the baseline SPECT study, 300 MBq 99mTc-HMPAO was injected. After i.v. administration of 0.1 mg/kg diazepam, 2nd dose of 600 MBq 99mTc-HMPA0 was given. Brief Cognitive Rating Scale was performed in 6 subjects just before the baseline injection (mean scale:57.33±0.75) and after i.v. diazepam before second 99mTC-HMPAO injection (mean scale: 57.16±i.o7). Their results were compared to those of subjects given no activation test. The mean counts/pixel was calculated for 9 ROIs on 8 sequential trasaxial s l i c e s and for cerebellum. L e f t / r i g h t region, r e g i o n / o c c i p i t a l c o r t e x , r e g i o n / c e r e b e l l u m and region/hemisphere ratios were determined for each region. After diazepam, ratios of right and left prefrontal, right parietal and temporal regions were changed significantly. The mean left/right hemisphere ratio was decreased significantly after diazepam with activation (1.025 vs 1.002, p=0.001), but not in patients without activation (1.018 vs 1.019). The mean frontal/cerebellar cortex ratio of subjects without activation was significantly higher than those of other group, either at baseline (i.011 vs 0.971) or after diazepam (1.013 vs 0.944). According to our results, the decrease of CBF in left hemisphere is more remarkable during activation, whereas CBF decreases significantly at rest in both frontal and right parietotemporal regions in comparison to other regions.99m Tc-HMPAO/split-dose injection method used in this study seems to be a promising tool in the evaluation of cerebral challenge studies. R.Mielke, K.Herholz, U.Pietrzyk, A.Jacobs, K.Wienhard and W.D.Heiss Max-Planck-lnstitut for Neurologische Forschung and Klinik for Neurologie der Universit&t KSIn. Germany Impairment of frontal HMPAO uptake has been described not only in many neuropsychiatric diseases such as Alzheimer's disease (AD), Pick's disease (PD), frontal lobe dementia, major psychoses and thalamic infarction but also in normal aging. We performed SPECT of Tc-99m-hexamethylpropylene amine oxime (HMPAO) and PET of F-18-fluoro-2-deoxy-D-glucose (FDG) under identical resting conditions within 3 h in 53 cases (23 AD. 14 patients with vascular dementia (VD), 2 PD, 1 patient with minor depression and 13 normal controls). Reduced frontal HMPAO uptake relative to whole brain uptake was seen in 20 cases (7 AD, 6 VD, 2 PD and 5 normals). 14 of these subjects had also impairment of frontal glucose metabolism (4 AD, 4 VD, 2PD and 4 normals) while there was no metabolic correlate of low frontal HMPAO uptake in 3 patients with AD, 2 patients with VD and 1 normal control. Low frontal HMPAO uptake is an unspecific finding that is frequently seen also in aged normal individuals and is not always accompanied by corresponding reduction of frontal glucose metabolism. Logemann J., Kocher F, Grab B M , Reske S.N. Dept. Nuclear Medicine, University ofUlm, Ulm, Germany Immunoscintigraphy of bone marrow with Tc-99m-labelled anti-NCA-95-antibodies has been used for efficient detection of skeletal metastasis in a variety of malignant tumors. Although sensitivity for detecting skeletal metastasis is regarded as high, some authors reported a very low specificity of only 11% of this procedure for detecting metastatic skeletal deposits.Therefore specificity of immunoscintigraphy was tested in I09 consecutive patients (m:~62:47), mean age 47 years (9-91) between 9/92 and 12/93. Clinical indication for the investigation was localiSation of potential inflammatory lesions in patients without indication of malignant disease. After i.v. injection of 420 (380-460) MBq 99m-Tc-NCA whole body scintigraphy was peformed about 4 hours p.i.. Scans were visually assessed for presence of photopenic lesions . In 88 patients out of 109 we found a completely homogenous hematopoietic bone marrow. Additionally we found peripheral focal increased activity as a sign for inflammation in 47 patients. In 13/21 patients bone marrow defects resulted from bone marrow biopsy (3 pts), proven spondylodiscitis (3 pts.), state after surgery (3 pts.), acute compression fracture of a single vertebral body ( 2 pts.), total hip prothesis (1 pt.), and known hemangioma of vertebral body (1 Pt). Among the residual 8 patients there were two patients with fever of unknown origin and spondylodiscitis was supposed but not yet proven. 6 patients showed solitary unexplained defects.These were solitary lesions in2 patients located in lumbal vertebral body V, in one patient in lumbal vertebral body III/IV, in 2 patients in the iliosacral joint and in one patient in pubic bone. In summary we found in only 6 of 109 patients (5.5%) unexplained photopenic defects in bone marrow. We conclude that immunoscintigraphy of hematopoietic bone marrow shows a homogenous bone marrow scan pattern in 95 % of a medium aged patient population. These data suggest a rather high specificity of bone marrow scintigraphy used for evaluation of metastatic spread to skeleton. Cognitive activation studies concentrate on cortical activation and very little attention is paid to the cerebellum. We studied the cerebellar activation in 2 groups of subjects during 2 visuospatial tests. Group 1 (O1): 7 patients (mean ag~75.7; MMSE=17.5) fulfilling the criteria of the NINCDS-ADRDA work group for probable Alzheimer% disease (AD) and 5 elderly controls (mean age=71; MMSE>24). Group 2 (02): 11 non demented patients with objective memory disorders (mean age=67.1; MMSE=27.1) and 4 normal controls (mean ag~58.2; MMSE=28.7). Each subject underwent two SPECT studies: one during cognitive stimulation (STIM) and one during baseline conditions (BAS). For 01, STIM consisted in a visuospatial task and for (32 in a visual memorization task. During BAS, all subjects were looking at a blank sheet. For each study, 740 MBq of 99mTc-HMPAO were injected via an IV line during the tasks. One hour later, imaging was performed with a conventional rotating gamma camera. 128 projections of 25 seconds each were gathered over 360 degrees on 64x64 pixels matrices. The SPECT data were analyzed on recortsa-ucted lateral views of each hemisphere using the Talairach arias localization system with automatic ROI definition. The activation effect was measured for each ROI by the index: (STIM-BAS/BAS) x 100. In normal patients, a significant cerebeilar activation was observed on the right side (11% for G 1;4.8% for (32). In AD patients in G 1, this activation was significantly lower 0.2%; p<0.05) as well as in patients with objective memory disorders in (32 (-0.55%; p<0.01). Beside the cerebellum, in normals, right associative visual cortex was activated in G1 and right inferior temporal region in (32. These results point out the involvment of cerebellum in cognitive tasks. They also question the use of this region as an internal reference due to its sensitivity to both conditions of injection and pathology. Dept. Radiology III and *Surgery III University of Ulm, Germany In a current prospective study we investigated the uptake of (fluorine-18) 2-deoxy-2-fluoro-D-glucose (18-FDG) in 6 patients (4 female, 2 male, range 14- Fluoride scintigraphy has been used in ~he past to evaluate skeletal flow. PET permits quantitative assessment of regional flow and tracer influx rate, and permits tomographic imaging of the skeleton. We investigated the bone blood flow (BBF) and influx rate (K) in 5 patients with a remote femoral neck fracture that was treated with a high risk for developing ostenecrosis. The contralateral hip was normal. A dose of 300 MBq 18 F-was administered iv and dynamic imaging performed over 60 rain. Plasma fluoride clearance was measured from arterial blood samples. With kinetic modeling diffusion rates wer~ est!mated between plasma, extra-cellular fluid and bone compartments . Net Fluoride influx K was used as measure of remodeling rate. For every patient the flow in the affected head was higher than the contralateral control. Necrosis was seen as absent fluoride uptake, accompanied by a hyperactive rim. Internal derangement is found among the most frequent disorders of the temporomandibular joint (TMJ), characterized by a disruption of the internal aspects of the TMJ with abnormal relationship and structural alterations of the components. A classification is possible according to Mill findings. However, clinical observations not always coincide with MRI results. Aim of this prospective study was to detect osseous changes of the TMJ with high-resolution SPECT and to correlate scintigraphic results with different stages of the disease. 37 patients with suspicion of internal derangement were investigated -ivith 555-740 MBq Tc-99m-DPD using planar and SPECT technique. SPECT was performed with a 3-headed camera equipped with an UHR collimator (Multispect 3, Siemens), matrix size 128x128. Visual and semiquantitative evaluation was carried out by two independent observers. Uptake values greater than those in the ipsilateral petrous bone were considered as pathological. MRI {mages were obtained in 69 TMJ/37 patients: Stage I (n=17) displacement of the disc with reduction, II (n=4) nonreducing disc, III (n=20) significant deformity of the disc, moderate osseous alterations and/or adhesions, IV (n=4) progressive osteoarthrosis. All TMJ could be discriminated with high resolution by SPECT. Pathologic uptake was seen in 31/69 TMJ, all of them having positive MRI findings: n=l 1 belonged to stage I, n=2 to stage II, n=14 to stage III, n=4 to stage IV. The results of this study indicate a good correlation between SPECT and MRI findings in the later stages of internal derangement. False positive results have not been observed. The diagnostic benefit of SPECT seems to lie in the detection of minimal osseous changes in the early stages of the disease. R6ntgenologic arthrography (RO.A~)and bone scintigraphy are diagnostic procedures used for evaluation of possible total hip prosthesis (THP) loosening. In this study, both examinations are combined and nuclear contrast imaging is added. 107 patients were i.v. injected with 600 MBq Tc-99m-MDP. Thereafter, standard 116.A. was performed. The radiographic contrast medium Omnipaque 300* was mixed with insoluble In-Ill colloid (5 MBq per 20 ml). After completion of the R6.A., nuclear arthrography (Nu.A.) was performed: multiple view, dual isotope images fln-Ilh 247 keV peak only) were recorded. Images w e r e interpreted by superposition of the In-111 image and the corresponding Te-99m-MDP image, the latter serving as a landmark for the position of the THP and osseous structures. 33% of the acetabnlar and 29% of the femoral components were uncemented. Filling of bursae -causing overprojection of In-111 over the joint spaceand occasional intraarticular In-lll resorption may interfere with image interpretation. In conclusion, Nu.A. is a sensitive technique for detection of THP loosening, offering significant added value over R6.A. alone, especially for evaluation of the femoral component. RO.A. remains necessary not only for adequate deposition of the contrast agents but also for detailed evaluation of osseous structures. G.Westera. A. Buck, C. Burger, K. Leenders*, P.A. Schubiger*, G.K.v.Schulthess. Division of Nuclear Medicine, University Hospital, Zurich, * Paul-Scherrer-Institute, Villigen, Switzerland. [I-123]Iomazenil is well known as a benzodiazepine receptor tracer for SPECT in epilepsy. We have prepared [C-11] iomazenil by methylation of demethyliomazenil with [C-11] MeI, which makes a direct PET-SPECT comparison with [123I]iomazenil possible. Five healthy volunteers were studied. After i.v. administration (4 min infusion) dynamic PET (during 90 min) and SPECT (during 270 min) scintigrams were made. The plasma input functions were corrected for metabolites by chloroform/water extraction of arterial (PET) or venous (SPECT) blood samples. The data were evaluated by fitting the tissue time activity curves to a three compartment model yielding K1 (the rate constant for blood-tobrain transport) and the distribution volume DV. The parameter variance in quantitation tasks is usually assumed proportionalto the vadance of the image data. While this assumption is valid for certain simple tasks, e.g., calculation of the mean activity concentration within a ROI, it may not always be valid for more realistic tasks, e.g., estimation of activity within a lesion whose size must also be estimated from the data. For these nonlinear quantitation tasks, the Cramer-Rao bound (CRB) also predicts a linear relationship between parameter variance and data variance. At low signal-to-noise ratio (SNR), however, the CRB may not be achievable. We compared quantitation performance in nonlinear quantitation tasks based on CRB calculations and Monte Carlo simulation. We modeled a spherical object embedded in a uniform background (BG), imaged by a system with a Gaussian PSF (FWHM 4 pixels). We calculated the CRB for the simultaneous estimation of the activity concentrations of the sphere and BG and the sphere diameter. We determined these 3 parameters by maximum-likelihood estimation (M LE) from simulated data (adaptive Gauss-Newton algorithm), calculating the parameter variances over 1000 replications per condition. In regimes of discrepancies between CRB and MLE, the estimation was repeated with the Nelder-Mead and the simulated annealing algorithms. We varied the sphere diameter (3-32 pixel), the axial length of the data set (1-16 slices), the pixel noise (white Gaussian noise with variance 10-3-t05), and the object contrast (activity concentration in the sphere 1-200, in the BG 100). At high SN R ML E achieves the CRB; i.e., it is efficient in the statistical sense. The parameter variance is proportional to the pixel variance. At low SNR, when the coefficient of variation (CV) for the nonlinear parameter (size) is larger than10%, the variance of the ML-estimates for the linear parameters exceeds the CRB and is no longer proportional to the pixel variance. At high SNR, the parameter variance for nonlinear quantitation tasks is proportionaltothe variance of the data; herethe CRB predictsthe best possible performance. At low SNR, however, the usual assumption of proportionality between parameter and data variance may break down. This implies, e.g., that averaging estimates over several low count images leads to higher qu antitation errors than estimating from the sum of the images. As the potential of image investigation of in vivo human biochemistry has been well validated, nuclear medicine must now turn its attention to the development of original radiopharmaceuticals with unique biochemical properties. For receptor studies in SPECT, numerous radioligands htbelled with 1-123 have been described. They are mostly antagonists and possess high affinity for binding sites. One should be careful in the interpretation of "receptor images" since these ligands are initially distributed with flow and then may demonstrate an uptake which may not be necessarily correlated with receptor density. For example, PET data obtained with C-11 MQNB indicate that its cardiac uptake represents only flow at all times after injection. For C-11 Flumazenil, early cerebral cortex uptake images are mostly flow images while late uptake images are more correlated with receptor density. A precise understanding of receptor ligand uptake can be obtained with PET through dynamic acquisitions and compartmental modeling to quantify receptor binding parameters (density Bmax and affinity Kd). SPECT technology does not allow so far rapid dynamic imaging of receptor ligand distribution and compartmental modeling cannot be obtained. Consequently, in SPECT, the interpretation of the distribution of a receptor ligand is not straight forward and simplifications are needed. A transfer of knowledge from PET to SPECT may be an adequate mean for establishing simple and direct ewlluation of SPECT images. For exanlple, fi'om the modeling the striatal uplake with Br-76 Lisuride on D2 receptors, one can show that, all parameters being kept constant, Bmax is well correlated with the striamm to cerebellum ratio of radioactive concentrations S/C. Atthough this conclusion cannot be directly extrapolated in patients, the ratio S/C has been proved to be useful in clinical practice. In conclusion, the future impact of receptor Iigands in SPECT depends on the selection of those radiopharmaceuticals with adequate pharmacological characteristics allowing their radioactive distribution to parallel specific binding. A COMPUTER MODEL TO ASSESS RADIOACTIVE GAS DISTRIBUTION WITHIN THE LUNG A computer model has been developed to simulate the transport of short-lived radioactive gases within the lung. The erect lung is divided into upper, middle and lower zones. Associated with each zone is an alveolar compartment and a regional deadspace compartment; the deadspace compartments are connected via a common deadspace volume. All compartment volumes are derived from Weibel's Lung Model A (1963). The alveolar compartments are trumpet shaped, corresponding to approximately the final 6 mm of distal airways and 90% of the total lung volume. The alveolar compartment is divided into 21 subcompartments (radial-slices). The regional specific ventilation, breathing rate and pattern, inspired gas concentration profile and radioactive half-life are taken into consideration. Gas movement in the deadspace compartments is considered to be by convection only and in the alveolar compartments by convection and diffusion. Using the model, the feasibility of utilising radioactive gas washout data to determine regional specific ventilation or gas-turnover in patient studies has been assessed. For example, regional specific ventilation can be deduced from the 81Krm washout time-activity curves, with a typical error of 13% (normal young adult). Including regions of impaired function within the model gives errors of 40%. In conclusion, the computer lung model is a useful tool to simulate the distribution of short-lived radioactive gases within the lung and has demonstrated that existing quantitative techniques are inaccurate when applied to patient data where pulmonary airways abnormality is present. [ 1-11C]-acetate has been recognized as a suitable tracer for assessing myocardial oxidative metabolism with dynamic PET. The close correlation between tissue clearance and oxygen consumption has been demonstrated using mono-and bi-exponential fitting as well as mean transit time approaches. A direct biochemical interpretation of the various parameters could not be given up to now. We have developed a detailed kinetic model which incorporates the known information of the metabolic fate of acetate in myocardinm in order to investigate which factors influence the actual behaviour of the tissue response. Our simulations show that the reproduction of measured impuls responses requires at least a 4-tissue-compartment model. Within our model the relation between the parameters of the usual mono-and bi-exponential fits and the rate constants of the model have been established. Model simplifications are discussed. Further, we address the problem of adequate corrections for spillover and recovery which are necessary in order to assess myocardial blood flow in addition to oxidative metabolism. We show that the formal treatment of spillover as effective fractional blood volume leads under realistic conditions implicitely to a rather good de facto recovery correction. Under these circumstances it is therefore erroneous to perform an additional recovery correction as has frequently been done in the literature. We conclude that the simultaneous quantitative assessment of myocardial blood flow and metabolism with [1-11C]-acetate is feasible with effective one-and two-tissue compartment models. Exponential fitting should generally be avoided because of the bias introduced by the effects of finite input duration and recirculation. M.Possa R.Sara L.Ruffini M.Milells R.Cozzi~P.0rlandi ~ F. Spinelli Nuclear Medicin Department Division of Endocrinology ~ Niguarda Hospital, Milan Italy lll-In-Pentelreoflde selutlgraphy In pituitary adenomas. The somatostatln (SS) analog l ll-ln-Pentetreotide has recently allowed to disclose in vivo the presence of SS receptors on pituitary adenomas. We studied 47 patients with pituitary adenoma. Planar images of the brain were acquired after the injection of 110-200 MBq 111-In-pentetreotide. We scored the images by an "uptake index" ratio between the adenoma radioactivity and the mean intracranial activity). In 4 patients without pituitary disease the mean score was 2 (range 1.8-2.2).GH secreting adenomas (n=18): the mean U.I. was 3.8 +/-0.4 A direct co=elation (r=0.54; p>0.05) was found between UI scores and the percentages of G H decrease after acute SS injection (100 gamma so), calculated as mean of the first 6 hrs GH levels vs baseline. In 3 patients with NMR evidence of empty sella, the scan did not visualize any intrasellar accumulation of pentetreotide.Sllent GH secreting adenomas (n=3): U.I. was very high (4.8, 9.6, 38); SMS treatment markedly depressed the accumulation of the ligand in the patient with the highest score.Non functioning (NF) adenomas (n-22): mean UI was 4.1 +/-0.9. Scan was positive in 14 (63%) patients. This % ofpositivity is close to the frequency of SS receptors obsen, od in these minors in vitro. In 6 patients with positive scan, long term SMS treatment did not change the accumulation of llgand neither the size of adenoma.]PRL secreting adenomas (n=4): UI was low (moan score 2.5).Conclusions: Pentetreotide scintigraphy shows the presence of SS receptors in a large portion of pim/tary tumccs. In aetomegaly the observed correlation with GH changes after SMS indicates their ftmofionality. In NF adenomas, the poor results so far obtained with SMS treatment on tumor size even in patients with positive SS receptors, point out the lack of fanctional role of the receptors evidenced by scintigraphy in controlling cell proliferation. It is well known that the image resolution of reconstructed PET images influences the quantitation of the observed activity concentration. The lower the image resolution the more unterestimated is the activity uptake in small structures due to the partial volume effect. The aim of this work was to investigate the influence of reconstructed image resolution on the kinetic analysis of dynamic PET data, i.e. on the rate constants resulting from a nonlinear regression fitting analysis of the time-activity curves. Dynamic sequences of brain images recorded for 60 min after intravenous injection of F-18-deoxyglucose (FDG) in 4 patients were reconstructed with a Harming filter and 4 different cutoff-frequencies leading to an image resolution of 5.5, 7, 9, and 11 nun (full width at half maximum, FWHM). Cortical regions of interests (ROI) were defined at an isocontour level of 50% at the maximum of the FDG-images summed from 30 to 60 rain after injection. The ROIs became larger with decreased image resolution. Using these ROIs cortical timeactivity curves were obtained. The plasma time-activity curve was derived from arterialized venous blood. Applying the well-established three-compartment model for FDG the rate constants were determined by a nonlinear regression fitting procedure, which was based on the Marquardt-Levenberg algorithm. For the best image resolution of 5.5 mm FWHM the resulting values of K1, k 2, k 3 and k 4 were 0.121+0.011, 0.223±0.076, 0.116x'-0.026 and 0.005_+0.005, respectively. All rate constants became higher when the image resolution was decreased. With the lowest image resolution of 11 mm FWHM K1, k2, k 3 and k 4 increased to 105±5%, 134±33%, 113-+15% and 175±86%, respectively, compared to the results for 5.5 mm FWHM. This investigation demonstrates that not only static PET data, but also dynamic ones are dependent on the image resolution. As known from animal research (Schmidt et al., JCBM, 1991) , the high increase of k 4 might be caused by effects of tissue heterogeniety which become higher for lower resolution. We used 7mCi of 99m-Tc-MIBi iv. and imaged the neck from anterior (first: 16 frames of I s, secondly: 16 frames of I min, thirdly: static images up to 3 hrs). Evaluation was based upon visual interpretation and computer analysis; the functional state of the thyroid was characterized by Iodine-123 uptake and clearance. The initial perfusion was greater in hyperfunctional thyroid adenoma and parathyroid carcinoma than in parathyroid adenomas; it was inconspicuous in normal-and hypofunctional thyroid nodules. The wash-out of MIBI from thyroid tissue was found proportional to the functional state of the thyroid ranging between 35 and 115 min effective half-time (mean 64 min). The wash-out of MIBI from parathyroid adenomas yielded the same mean value of 64 min. We are led to believe that the perfusion-and wash-out analysis of MIBI in the neck aids in differentiating the functional states of the thyroid but does not obviate the need for dual isotoDe techniques. Bailliez A., Nocaudie M., Huglo D., Ziegels P., Proye C., Marchandise X. Aim. This study was designed to assess 99~Tc.MIBI scan with respect to any parathyroid lesions, as they are found by surgeon. p_~tients. Among 65 investigated patients by MIBI scan, 23 patients with primary hyperparathyroidism were cured by snrgery and had fully documented data. 91 glands were systematically exhibited by surgeon : 34 were abnormal (2 ectopic Methods. 550 MBq 99~Tc-MIBI were injected, images were performed 20 mn and 2 h later ; ~-~3I was then injected and thyroid scan was obtained 2 h later. Parathyroid scan was + if abnormal focus corresponded to surgical finding, -if not. A ROC analysis was performed to study the mass threshold. Evolution of Contrast Ratio lesion/thyroid from 20 mn to 2 h (ECR) was studied in 15 + lesions with normal thyroid. Results. When multiple lesions, 1 at least was detected in 6 patients (over 9), but all in only 1.12 adenomas >300 mg (over 13), 3 < 300 mg (over 8) and 2 hyperplasias (over 13) were seen, In our prospective study, we investigated during the last 3 years 50 patients (pts) with suspicion of parathyroidal adenoma on a routine basis with 99Tcm-MIBI. 31 of them -mostly with symptomatic hyperparathyroidism -underwent surgery, 20 patients with established thyroidal nodules were added, 15 pts with hot and 5 with cold nodules. All pts were scanned 10 min., 1, 2, and 4 h after intravenous injection of 350 MBq 99Tc~"-MIBI and digital scintigrams were acquired. The tracer kinetics was analyzed for the site of suspected parathyroidat adenoma (showing up as hot spot or known after surgery), the thyroid, and soft tissue of the neck. The activity of suspected lesions was compared with thyroidal activity and the ratio was found to increase with time for parathyroidal adenomas. 14 of the 31 pts, for whom histology is available, were diagnosed true positive. 3 of them were ectopic, intrathoracic in 1 case, autografts in the foreman in 2 cases. 2 findings were true negative, the remainder were false negative resulting in a sensitivity of app. 50 %. The scintigraphic finding for the 19 pts, who were not operated and who mostly were under dialysis, was negative and the final diagnosis most likely excluded an adenoma. None of the pts with hot or cold thyroidal nodules showed any lesion, that could be misinterpreted as a parathyroidal adenoma. The sensitivity of the method was found to be moderate in our unsetected patient population. However, the specificity is very high (no false positives in our study), as proven by histological comparison and in the prospective study with selected thyroidal disease. 111In-LDL has been shown to have preferable binding characteristics both in-vitro and in-vivo as compared to 99mTc and 123I. LDL was isolated by sequential ultracentrifugation and labeled using cyclic DTPA-anhydride. 111 In-LDL-liver imaging (500 ~Ci; 32 minutes, 64 frames, matrix 128 x 128) was performed after an overnight fasting. Time-activity curves over the liver, total liver uptake (%) and plasmatic decay were monitored and compared to in-vitro binding data (125I-LDL). There was a s~ng correlation between in-vitro binding results and in-vitro trapping by the liver. Therapeutic interventions (diet, n=8, drugs [clofibrate analogues, n=14, HMG-CoA-reductase inhibitors, n=8] and LDL-apheresis, n=5) resulted in a significant improvement in in-vitro and in-vivo LDL-binding, which significantly correlated to LDL-cholesterol lowering. B. Erbas. N. Elahi, M.K.Ahmedi, N. Atakan, A. Karaduman, Z. Koray, G. Erbengi, S. Akkaya. Hacettepe University, Ankara-Turkey. Nephrotoxicity is a major problem in patients treated with cyclosporin A (CyA). It is used after transplantation and for the treatment of various autoimmune disorders. To examine the short-and long-term renal effects on normal kidneys and circulating endothelin levels, we investigated renal perfusion and glomerular function after oral CyA and one month later. Study was performed on 18 patients (mean age: 28.7+14.3, range: 7-58 years) with diagnosis of psoriasis or alopecia (duration: 10.2+7.9) whose renal functions were normal. Renal function of pts were assessed using 99mTc-DTPA scintigraphy. Following i.v. administration of 370 MBq 99mTe-DTPA, 64 serial images/per sec and 80 serial images/per 15 sec. were recorded. GFR was calculated according to the Gates' technique. Perfusion index (PI) was determined using Hilson's method. All patients received 5 mg/kg/day of CyA. Renal scintigraphy was pertormed at baseline, at 2rid hr following Cy A administration and after one month. Simultaneously blood levels of CyA (2 and 4 hrs after CyA administration), circulating endothelin, plasma and urine beta-2 microglobulin(B-2) were determined using RIA. The mean GFR was 81.4+16 ml/min (baseline). Following CyA, total GFR was decreased in 12 pts acutely, whereas it was increased in 4 and remained unchanged in 2 pts. CyA levels were 400.3+330 ng/rnl, 399.9+222 ng/ml and 269.77+320 ng/dl, respectively at 2nd, 4th hrs and one too. later. The mean endothelin level (10.6+7.8 pg/ml) was increased acutely (26.9+22 pg/ml). B-2 levels were within normal limits. The mean percent change of GFR (0.11+22, range: -38, +57,7) and mean percent change of P1(-4.97+36, range: -87.9, 87.2) were not correlated acutely with CyA, endothelin or B-2 levels. However, % change of endothelin at 2nd hour was significantly correlated with CyA !evel (p=0.02 r=0.78). One too. later, the mean GFR was changed to 74.4+21.2 ml/min, insignificantly. The mean % change of GFR (-6.6+25.2) was not correlated with CyA and B-2 levels. Our results indicated that CyA might cause an insignificant reduction of GFR in patients with normal kidneys being independently of CyA levels immediately after oral administration of drug and at long-term. Acute increase of endothelin correlated with CyA levels might be responsible for acute functional changes. ~he MTT and T20 in OBS is significantly longer than in FG (p<0.001). The IU in ATN, AR and OBS is significantly decreased in reference to FG (p<0.001 in ATN and AR; p<0.0S in OBS) . The IU in NTX is similar to FG and significantly different from ATN and AR. A significant correlation was found between serum creatinine and IU values (r=-0.74, p<0.01).Patients' IU follow up corresponded in most cases to clinical evolution. In conclusion, MTT, T20 and IU are useful in evaluating kidney allograft function and may be of help in the differential diagnosis of post-transplant renal disfunction. The intrarenal reflux plays the key role in the etiology of reflux nephropathy and its detection is of utmost importance in evaluating possible damage in kidney with reflux. In 176 kidneys (113 children) with different degree of vesicoureteric reflux (VUR), dynamic renal scintigraphy with Tc-99m-DTPA in zoom mode was performed. From each study 6 functional images of mean time were generated, kidney contour superimposed on each, and time activity curves (TAC) over possible areas of increased mean time were generated. In these study we analysed only areas of increased mean time over the outer contour of the kidney which corresponds to the renal parenchyma. In later functional images of the mean time we found 53 focal retentions over the part of the kidney which corresponds to the renal cortex (33 in upper, 5 in middle and 15 in lower part of the kidney). TAC-s generated over these areas exibited a sharp increase of activity on the descending part of the curves. We propose that the return of activity from the collecting system to the kidney cortex represents intrarenal reflux. In our opinion, analysis of functional images of the mean time could be a method for more accurate detection of intrarenal reflux and indicating the children with high risk to acquirfe renal scarring. Coronal, sagittal and transaxial slices (CST-slc) from SPECT Tc-ggm-DMSA allow a good detection of renal scarring but are not easy to read also because they are oblique as regards the longitudinal axis (LA) of the kidneys. The aims of this study were: i) to obtain slices parallel (PA-slcl and perpendicular (PE-slc) to the LA of each kidney and a cylindrical multi-slice diagram (MSD) ut each kidney; 2) to evaluate the effectiveness of both MSD and PA+PE-slc for the detection of renal scarring, in comparison with planar images (PI) and CST-slc. 26 patients (age range 1-71 yrs) were imaged 2 hours after administration of 80-200 MBq of Tc-ggm-DMSA. Planar and SPECT studies were performed. SPECT data were processed both in the usual fashion (to obtain CST-slc) and with a new algorithm. During reconstruction, the SPECT transaxial slices of each kidney were rotated to annihilate the angle between the LA and the sagittal plane. So PA-slc and PE-slc of each kidney were obtained. From each PE-slc a count distribution angular profile was obtained and represented as a horizontal row of pixels of a matrix (cylindrical MSD). The PI, the CST-slc, the PA+PE-slc and the MSD of each of the 5 2 kidneys were analyzed separately. Upper, central or lower part of each kidney was considered as a positive zone if it contained scars. The positive zones were 52, 70, 81 and i01 with the four techniques, respectively. 33 positive zones were always observed. Some more positive zones (not always the same) were reported with each technique: 19 on PI; 37 on CST-slc; 48 on PA+PE-slc and 68 on MSD. In conclusion SPECT PA+PE-slc and especially MSD were easier to read and allowed to find more renal scars than PI or CST-slc. Despite angiographically successful interventions, residual ischemia in the perfusion territory of the treated coronary artery is not uncommonly observed in postinterventional perfusion scintigrams. Intracoronary ultrasound (IVUS) studies have demonstrated that the extent of residual intracoronary plaque and obstruction may be underestimated by angiography. Therefore, 24 patients with angiographically successful (residual diameter steneses < 50%) coronary interventions (techniques: 14x PTCA, 6x stenting, 2x directional atherectomy, 2x rotablatien; vessels: 15x LAD, 7x RCA, 2x RCX) were examined by IVUS immediately after the intervention. 24 and 48 h after the intervention all patients underwent myocardial scintigraphy with 99m-Tc-methoxyisobutyl-isonitrile after dipyridamole stress and at rest using a triple head SPECT camera. The perfusion territory of each treated vessel was estimated from the coronary angiogram and assigned to a segmental left ventricular model. Areas of myocardial ischemia were assigned to the same segmental model. The residual area stenosis was determined from IVUS images as (area within lamina elastica intema -luminal area) / area within lamina elastica interna. 13/24 patients had myocardial ischemia during dipyridamole MIBI-SPECT. Median area stenosis was 71% in patients with ischemia and 53 % in patients ivus stenosis_> 60% no yes without ischemia (p=.008; Mann-Whitney " --yes I test). The best concordance between ~_m 2 11 residual area stenosis and residual g ~ no 8 3 ischemia was found for IVUS area stenoses _> 60%. Patients with stress induced myocardial ischemia immediately after successful coronary interventions show high grade residual stenoses when examined by IVUS which could at least partially explain the discrepancy between angiographic and scintigraphic findings. Whether DMSA is taken up by the tubular cell directly from peritubular capillaries or by reabsorption following filtration of the unbound fraction in plasma, the rate of uptake should reflect tubular function. Since MAG3 and hippurate are taken up even in ATN, they are unlikely to be sensitive markers of tubular injury. The aim of this study was to examine the feasibility of dynamic DMSA imaging, with measurement of renal extraction efficiency (EE) of DMSA, for the assessment of tubular injury. Renal blood now 0tBF) and DMSA EE were measured using quantitative techniques previously developed for DTPA. These were respectively based on the first-pass integration technique and the Patlak plot applied up to 15 min after injection. Since DMSA behaves almost as a pure intravascular marker, RBF can be obtained in units of ml/min. 24 patients were studied; 14 with native kidneys and 10 with recent transplants. As expected in this heterogeneous group, RBF was highly variable, with maximal values approaching 1000 ml/min in some transplants.The Patlak plot was consistently bi-phasic, giving a higher EE from 40 sec to 3 rain than over 3-15 rain. EE in both phases was consistently higher in native than in transplanted kidneys. In the first phase, it ranged from 1.5 to 7.3 and in the second, from 0.65 to 5.8. Five transplant recipients with biopsy documented ATN had low values of EE, 1.05 (sd 0.5) for the first and 0.28 (0.06) for the second phase, whereas in 5 with vascular and/or pareecbymal rejection, it was significantly higher, 2.35 (1.3; p<0.05), and 1.45 (1.0; p<0.05), respectively. The range of the second phase EE for the ATN group (0.2147.38) did net overlap with that for the rejection group (0.4-2.8), We conclude that dynamic DMSA imaging yields useful functional data, including RBF, and may be able to distinguish between rejection and causes of tubular damage, such as ATN or cyclosporin toxicity° The timing of the initial higher EE is consistent with DMSA filtration; if 80% was protein-bound in plasma and filtration fraction was 20%, then EE over this phase would be 4%. The subsequent EE reflects tubular uptake. Coronary angiography is regarded as the gold standard in the detection of coronary artery disease (CAD). Therefore, myocardia) perfusion scintigraphy is frequently regarded as false positive. Since the endothelium plays a pivotal role for coronary blood flow regulation, we tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature even in the absence of obstructive CAD could contribute to the failure of coronary blood flow to increase. In 16 patients (p) with normal perfusion and 14 p with exercise induced ischemia evaluated by TI-201 SPECT, coronary blood flow (CBF) was measured after infusion of the endothelium-dependent dilator (EDD) acetylcholine (ACh, 10 .8 to 10 .6 M), and of the smooth muscle relaxant papaverine (Pap, 7mg) into the LAD via a Doppler catheter. Flow-limiting epicardial CAD was excluded in all p. After ACh, CBF increases were significantly greater in all normal p compared to p with exercise induced TI-201 defects (ACh lOSM: 4 3 . 3 + 5 5 . 4 % vs 1 4 . 4 + 1 2 . 6 % NS, 10-7M: 1 1 9 . 8 + 5 9 . 5 % vs52_+39.8% p=O.O01, 10-6M: 173.8_+79.9% vs 7 2 . 8 + 2 8 . 5 % p=0.002). No difference was found after Pap: 360.6_+141.4 vs 3 4 2 + 7 6 . 6 % NS. The ACh/Pap-ratio was significantly lower (p<0.0001) in p with myocardial perfusion defects. Thus, impaired endothelium-dependent dilation of the coronary resistance vasculature contributes to exercise induced myocardial ischemia detected by TI-201 SPECT in p with nonobstructive CAD. Raunaud's phenomenon is frequent in patients (pts) with systemic sclerosis (SS). To examine whether cold-induced Raynaud's phenomenon in SS may involve the coronary arteries, we examined 20 pts with known SS. Age was 52±12 years (range 38-66 years), duration of SS was 7,2±5,5 years (range 6 months-17 years), 18 pts were women. 19 pts had definite Raynaud's phenomenon with duration i0~7,6 years (range 3-24 years); 4 pts had esophageal involvement. All p~s underwent dipyridamole-thallium SPECT imaging (0,56 mg/kg for ~ min) to exclude the p o s s i b i l i t y of myocardial ischemia.Within one week thallium SPECT imaging was repeated after immersion of both hands to ice water (tem~erazure 0 ° to 2°C) for 3 mir (Cold pressor, CP). During CP systolic blood pressure rose to 172~27mn~%, diastolic blood pressure rose to 99±14 mmHg and heart rate to 88±15/min. No pt develooed ischemic thallium defects during dipyridamole thallium imaging. During CP 6 pts developed definite ischemic thallium defects(2 anter i o r l y , 2 i n f e r i o r l y , 1 septal, i l a t e r a l ) . All pts with cold-induced defects had Raynaud's phenomen. Compared to pts without cold induced defects, pts with defects had similar rise in blood pressure and heart rate but a sign i f i c a n t l y longer duration of Raynaund's phenomenon. In conclusion, pts with longstanding SS and Raynaud's phenomenon may present abnormal myocardial perfusion during cold pressor stimulation, indicating a CoronaryRaynaud's phenomenon in those pts. P. Theissen, M. Reichenbach, E. Voth, K. Scheidhauer, H. Schicha Klinik und Polildinik ftir Nuklearmedizin, Universitiit zu K6in, K61n, Germany Thallium1201 myocardial scintigraphy with dipyridamol-(Dipy)-stress is considered to be equivalent to the scintigraphy after ergometer-(ergo)-stress. In order to ensure the finding "ischaemia", quantitative wash-out evaluation seems to be advautage0us~ Though, the value of the redistribution analysis for detection of ischemia after Dipy-stress has been judged differently. In order to prove the significance of the redistribution analysis thallium-SPECTmyocardial scintigraphy (MySc) after Dipy-stress wash-out was calculated in 48 patients with coronary artery disease (CAD) verified by coronary angiography (CA). In 42 patients MySc was performed only after Dipy-stress and in 6 patients with a 14 day interval after both, Dipy-and ergo-stress. 0.75 mg/kg body mass dipyridamol and 74 MBq thallium-201 chloride were administered. The time interval between stress and redistribution scintigram was 3 hours, polar tomograms resulting from stress and redistribution scintigrams have been divided into 17 Regions of Interest (ROI). For the total 144 ROIs after Dipy-stress and additionally for 18 ROIs after ergo-stress wash-oat rates were calculated. The wash-out rates belonging to the 3 vascular regions of coronary blood supply were referred to the average value of the 2 ROIs with the highest wash-out values. Thereby, a reduction of the washout by more than 15 % compared to the maximum has been considered as pathological. Coronary stenoses of 60 % or more deemed to be relevant. In 113/144 (79 %) ROIs corresponding findings between CA data and washout calculation occured. In 31 ROIs discrepancies were found. Most of the different findings occurred in multi vessel CAD (13 cases with either 2 or 3 stenosed coronary arteries). In 8 cases, ROIs with discrepancies between CA and washout data were affected by a myocardial infarct. Comparing Dipy-and ergo-stress, 12 of the 18 ROIs agreed. In 4 ROIs with discrepancies Dipy-stress and in the other 2 ROIs with discrepancies ergo-stress were positive for ischaemia. Herewith, the Dipy and ergo scintigraphy were conform with the CA data in 3 times, respectively. Wash-out calculation of the MySc after Dipy-stress shows similar results as the redistribution analysis of the MySc with ergo-stress. The results indicate that also for MySc after Dipy-stress wash-out calculation makes the results more reliable and should, therefore, be added to the routine MySc evaluation. A.Bortone*, F.Lauriero, D.Rubini, A.Chiddo*, P. Rizzon*, A. D'Addabbo. Depts. of Nuclear Medicine, *Cardiovascular Diseases -University of Bari-Italy Endothelium-dependent vasodilatation impairment seems to be responsible for perfusion defects in pts with angina and normal coronary arteries.The aim of this study was to verify whether Acetylcholine (Ach), in conjunction with perfusional scintigraphy (99mTc-MIBI SPET), was able to identify distrectual paradoxis vasoconstriction and quantify the perfu-sion defects. In 13 normotensive pts (3 male, i0 fe-male; mean age 52 yrs) with typical chest pain, negative stress test, absence of ischaemic signs after i.v. ergonovine and angiographically normal coronary arteries, Ach (10 -4 M) was administered in the LMCA for 1.5 ml/min and the coronary sinus flow achieved by thermodilution technique. At the end of perfusion, 500 MBq of 99mTc-MIBI was injected and SPET acquisition was performed 2 hours after. The day after, 99mTc-MIBI SPET was repeated in basal conditions. In 7/13 pts 99mTc-MIBI SPET showed reversible myocardial perfusion defects in the left coronary related area, affecting only part of the distribution area. The coronary sinus flow was reduced in all 7 pts, but not significantly. Ach induced typical angina and ST segment depression (> 1.5 mm) in 3/7 pts. 99mTc-MIBI SPET in conjunction with intracoronary infusion of Ach is a useful method to detect pts and quantify regional myocardial perfusion defects due to endothelium-dependent vasodilatation impairment. Nuklearmedizin, Universit~t Ulm, Ulm, Germany The dependence of the extraction fraction E on flow F in the human heart is essential for the noninvasive determination of myocardial blood flow. We investigated this flow dependence in the human myocardium by comparing the Rh-clearance (F'E) with the flow F determined by the Argon-method. For 5 patients (age 60.6±7.4a, 3/2=m/f) extraction was measured under rest and under dipyridamole (0.7mg /kg/4min) induced hyperemia. The fit of our results to the analytically derived dependence for a two compartment model (tissue and vascular compartment, P permeability, S surface) yields E = PS/(PS+F) , PS=(0.90±0.09)ml/g/min . (i) This result deviates for large and low flows from the standard formula determined by Mullani and Goldstein (for dogs) E = 0.55 exp(-bF) , b=0.22g*min/ml . ( We showed that their extraction fraction E is not equivalent to the usual unidirectional extraction fraction and that the data of these investigators are also adequately described by equation (i) with PS=0.87ml/g/min -a common value for mammals -if the usual unidirectional extraction fraction is used. The differences between both equations may cause the lower myocardial values for flow F obtained with equation (2) compared to flow measured by microspheres. Therefore we claim that the functional dependence of equation (i) should be used for the extraction fraction, as it is the theoretically consistent description for a two compartment system. JC Rooe, A Perkins, A van Hof, Q Davies, C Molthoff, W den Hollander, A Wilhelm, R Verheijen, M Frier, J Vermorken, A van Lingen, T Baker, E Symonds, P Kenemans. Free Univ Hosp Amsterdam, The Netherlands and celltech Ltd, Slough and Queen's Medical Centre, Nottingham, UK. hCTMOI is a CDR-grafted humanised IgG4 MAb binding polymorphic epithelial mucine (PEM) which is present on the membrane of secreuory epithelia and overexpressed in malignancies derived from these tissues. 13 Patients (pts) suspected of primary or recurrenu ovarian cancer were inj meted intravenously with 0.1 mg/kg In-IlI-hCTM01 macrocycle conjugate (100 MBq) . Radiochemical purity was > 96.4% (TLC) and immunoreactivity (coated antigen bead assay) was > 66% binding. All pus were assayed for circulating CA 15-3 prior ~o injection. Immune complexes were detected (HPLC) in all blood samples from 15 min post injection (pi). The mean biological T%B of IgG in blood in cancer pus was 61-+20 h, and longer in pus with high levels of circulating antigen (CA 15-3 assay). T h e mean biological T½~ of the complexes was 54-+13 h. Immunoscintigraphy up to 120 h pi showed malignancy in 6 out of 8 pts with surgically proven cancer. Bone marrow, liver and spleen were seen in all pts. Of the 5 pts with benign or borderline tumour, 1 was false positive. Mean (SD) tissue uptake (%D/kg) at surgery (6 days pi) was for tumour (T) 4.9-+5.3 (range 1.3-17.4), normal tissue (NT: mean of skin, fat, muscle and peritoneum) 0.7+0.6 (0.2-2.2), blood (B) 2.3+2.3 (0.5-6.4) and liver 22.1±ii.6 (5.4-35.6). Mean T/NT was 7.7±5.9 (2.4-19.8) and T/B 2.7-+1.7 (0.8-6.3). In one pt with a high CA 15-3 the highest tumour and lowest liver uptake was found. In conclusion, hCTMOI selectively targets ovarian cancer with positive immunoscintigraphy. The possibility of an inverse relationship between circulating CA 15-3 level and liver uptake requires further investigation. The MAb dose is now to be increased to 1 mg/kg to elucidate the effect of a higher MAb dose on complex formation and liver and tumour uptake. Kocher F., Stollfu8 J.C., Sch0nberger J.A., Logemann J., Bachor R. *, Hautmann R:*, Reske S.N. Staging criteria for lymph node involvement in kidney-and bladder cancer presumes actual biopsy of nodal tissue. Since glucose utilisation is markedly increased in a variety of malignant tumors and their lymph node deposits~ the feasibility of non-invasive assessment of lymph node involvement with FDG-PET was studied in 11 patients with bladder cancer and 10 patients with carcinoma of the kidney. After performing transmission scans for attenuation correction PET-Scans were acquired with ECAT-931-08-12 PET-Scanner ( Siemens-CTI, Knoxville TN ) 50 minutes after intravenous injection of 240 +/-60 MBq 18-FDG. The axial field of view was 30 cm Iterative reconstruction was performed in eight iterations and images were reconstructed in three views. To avoid artefacts due to 18-FDG contamined urine 20 nag furosemide was given i.v. and the urinary bladder was purged continuously with an irrigation catheter. Results were compared to histological findings of intraoperativly picked lymph nodes. PET-scans were classified correctly positive, when a focally increased FDG-uptake was found in all correCt anatomical sites of verified infiltrated lymph nodes. Pet scans were classified as Correctly negative when activity distribution in small pelvis and lower abdomen showed no focally increased uptake in major lymphatic pathways and histology of lymph nodes was negative. In patients with bladder carcinoma lymph node staging was correctly negative in 7 patients, correctly positive in 3 patients and false positive in one patient. In patients with carcinoma of the kidney, lymph node staging was correctly negative in 7 patients and correctly positive in three patients. Despite renal excretion even the primary tumor was detectable in 4 out of 10 patients with kidney carcinoma.These preliminary results suggest that 18-FDG-PET provides a highly promising tool for demonstrating or excluding metastatic spread to regional lymph nodes in bladder-and kidney carcinoma. Laparoscopy, CT of abdomen and pelvis, and the CA-125 m a r k e r are a l t e r n a t i v e s to "second-look" l a p a r o t o m y in o v a r i a n cancer. The A $UV of 3.08 ±1.68 was the cutoff s e p a r a t i n g b e n i g n from m a l i g n a n t tissue. Overall, PET had a s e n s i t i v i t y and s p e c i f i c i t y of 83% and 80%, c o m p a r e d to 82%, r e s p e c t i v e l y 53% of CT. In p a t i e n t s w i t h s u s p e c t e d r e c u r r e n t o v a r i a n cancer, PET had a sensitivity, s p e c i f i c i t y and a c c u r a c y of 58.3%, 95% and 81%. FDG PET is s u f f i c i e n t l y specific, e s p e c i a l l y in light of a n e g a t i v e CT scan, that it m a y obviate "second-look" operations. We conclude that FDG-PET can differentiate 2 subgroups of prostatic cancer. Glucose metabolism of one group equals that of benign hyperplasia while the other group, which mainly comprises patients with metastatic disease, is clearly hypermetabolic. Thus, identification of patients with high risk of progressive disease might be possible by PET and needs to be further investigated by long-term follow up studies. The sleep apnea syndrome (SAS) is comprised by daytime hypersomnolence, snoring, obesity and frequent cessation of breathing during sleep. Complications are alterations of blood pressure, brain pressure and cardiac output, lethargy, loss of cognitive functions and memory, and brain infarction as well. Aim of the study was (1) to find feasability of imaging rCBF during nocturnal phases of sleep apnea and (2) to document therapeutic effects of transnasal continuous positive airway pressure (CPAP) breathing on rCBF. 13 patients ( 12 male, 1 female, mean age 50 +/-9.8 y, mean body weight 107+/-13.6 kg) were suspected to have SAS as indicated by a device for ambulant SAS monitoring (MESAM box) and were enrolled to the study. Polysomnography (PS) was started in the late evening hours. Patients were injected during a PS-documented apnea phase with 700 MBq Tc99m-HMPAO by rapid inflush of saline solution into i.v. indwelling cannula. Injection took place between 2.00 and 4.00 hrs a.m., SPECT data acquisition at 7.30 a.m. Two nights later the investigation was repeated under therapeutic transnasal CPAP breathing. Two injections coincided with REM phase. Injection times were doumented to allow for precise analysis of PS. All SPECT studies were evaluated by means of a semiquantitative algorithm and regional perfusion indices were established. Under CPAP breathing a drastic improvement of the former pathologic sleeping behaviour could be documented, the arterial pO 2 saturation increased (p<0.02), the apnea index decreased (p<0.01) significantly. More patients attained deeper states of sleep (from I and II to III and IV). In 5 patients a suprafrontal hyperperfusion, in two pat. an additional increased basal ganglia perfusion could be found, five pat. revealed temporo-parietal decreased perfusion pattern. All findings improved under CPAP, in two patients normalizing completely. SPECTs of the REM phase showed increased occipital perfusion in spite of closed eyes, revealing hyperactivity of visual cortex. We conclude that HMPAO-SPECT is capable to image nocturnal regional cerebral blood flow. Frontal hyperperfusion is discussed to have two reasons: dilatation of brain vessels due to increased pCO 2 tension with superposition of frontal cognitive activation during pathologic light sleep behaviour. A Tc-99m labelled antibody has been used in 14 p a t i e n t s for imaging r e c u r r e n t p r o s t a t i c malignancy. 600 MBq of Tc-99m labelled CYT-3SI (Cytogen Corporation, USA) was administered, with planar imaging at i0 minutes, 6 hours and 24 hours and pelvic SPET at 6 and 24 hours. All patients had bone scans (BS) and immune scans (IS). 2 patients had negative BS and IS. 4 patients had positive BS and positive IS. In these patients, the IS picked up local soft tissue recurrence but not the BS lesions, while in one IS showed all BS lesions. In 6 patients with a negative BS and a rising PSA, IS demonstrated local recurrence. In 2 patients with extensive BS lesions, IS did not demonstrate any disease. Both had longstanding metastases and were responding to treatment. This procedure offers all the advantages of using Tc-99m and is comfortable for the patient, the entire study being completed in 24 hours with no special preparation. These early results seem to indicate that Tc-99m labelled CYT-351 may have a role in identifying soft tissue recurrence, especially in patients with a negative workup and a rising PSA. 126 patients suffering from epilepsy have been evaluated retrospectively for the predictive value of diagnostic imaging using MRI and interictal HMPAO-SPECT. In 106 patients these results could be compared to the EEG findings, the site of surgical intervention and the post-op outcome. 10 -30 minutes after Lv.-injection of 740 MBq (20 mCi) 99mTc-HMPAO a brain-SPECT was performed. MRI scanning included sagittal TI-, transversal proton-and T2-and coronal Tl-weighted IR-sequences and in most eases T2weighted TSE-sequences using a temporal angulation. Areas of hypoperfusion were seen in 113 patients, whereas only 13 patients showed an inconspiclous cerebral perfusion pattern. MRI revealed lesions in 74 patients and normal results in 52 patients. In 7 cases both techniques described defects, that did not match concerning their localization. The distribution of the remaining results is given below. Tc-99m-Bicisate is now available as a new tracer for cerebral blood flow (rCBF). We initiated a study aimed at evaluating its usefulness in the detection of epileptogenic foci. We report on the first 11 cases who underwent an ictal and iuterictal rCBF SPECT so far. All patients received an EEG and a MILl of the brain including transverse protonand T2-weighted sequences, as well as coronal Tl-weighted IR-and T2-weighted TSE-sequences using a temporal angulation. Prior to injection the radiochemical purity of the tracer was determined to be at least 90% in all cases using thin layer chromatography. Approximately 590 -770 MBq 99mTc-Bicisate were i.v.-injected 2 -20 seconds (mean 5 sec.) after the onset of a seizure. SPECT-studies were started 1 to 3 hours after injection, using an annular crystal SPECT-system (Ceraspect, DSI). lnterictal studies were performed 30 minutes to 1 hour after i.v,-injectiot~ of 740 MBq 99mTc-Bicisate using the same SPECT-system. MR/ was normal iu 7/11 patients. During interictal phase 10/i1 patients showed areas of hypoperfusion according to the EEG findings. Ictal SPECT-studies revealed significant changes in perfusion iuvolveiug especially these areas in all patients. Circumscript areas of total hyperperfusion were detected in 5 patients. These preliminary results indicate that Bicisate is valuable for the assessment of epileptogenic foci, if the tracer injection is carried out rapidly after the onset of a seizure, which underlines the value of a tracer with a high in-vitro stability over several hours. In addition ictal rCBF SPECT using high resolution SPECT systems is able to detect circumscript ictal hyperperfusion suggested to represent the focus itself in a considerable number of patients. This study was performed in order to correlate ictal CBF changes to seizure symptomatology and to estimate the value of combined video -EEG and HMPAO -SPECT findings for the presurgical lateralisatlon of epileptogenic foci. In 15 patients (18 -65 yrs) prolonged video EEG recording (mean 5 days) and HMPAO -SPECT (Siemens Multispect 3) were obtained during a seizure (HMPAO inj. 40-60 sec after seizure onset). MRI and a second SPECT study were performed in the seizure free intervall. Nine patients had temporal lobe epilepsy (TLE) while 6 patients suffered from extra -temporal seizures (ETE). For anatomical reference SPECT studies were realigned and superimposed to MRI images. rCBF changes between the two SPECT studies were estimated visually and localized on MRI images. Loss of consciousness, postictal amnesia and automatisms were associated predominantly with activation of the lower mesial and lateral portion of the temporal lobe. Additional activation of the lateral frontal lobe was also seen in 3 patients with automatisms. Two patients with paranoid symptoms revealed increased HMPAO uptake in the mesio-and laterofrontal regions as well as in the anterior basal ganglia. One patient with TLE showed an activation in one temporal lobe and in the contralateral frontal and parietal region, suggesting no direct contralateral temporal seizure propagation, as already postulated by electrophysiological investigations in man. Optical hallucinations were paralleled by CBF increase in the temporal lobe, basal ganglia, sup. and inf. occipital lobe. During seizure activity elevated CBF extended from the extratemporal focus to the ipsilateral occipital and temporal lobe or even in both mesio -temporal regions in the ETE -group. One case with negative motor seizures had a circumscribed rCBF increase in the prefrontal cortex. Lateralisation of the epileptogenic focus was achieved by SPECT in 90%, EEG 60%, and MRI (hippocampal atrophy) in 70% of the cases. In summary, high resolution SPECT combined with prolonged EEG recording considerably increases the accuracy of focus lateralisation and the knowledge on seizure propagation related to seizure symptomatology. W. Reiche l, J.Reel3 2, R. Save and effective surgical treatment for medically refractory epilepsy depends upon aeurate identification of the epileptogenic brain area. Confirmatory tests of focal functional deficits are applied to increase confidence in EEG-localization. The goal of this study was to compare the findings of tSFDG-PET and neuropsychological tests with the EEG-loealization in the presurgical evaluation in patients with medically refractory focal epilepsy. We examined 15 patients (12 females, 3 males, medium age 26,3 +14.4 years) with long-standing (17.7 -+10.2 years) medically refractory focal temporal lobe epilepsy by EEG-videometry, 18FDG-PET and additional 7 patients with neuropsychological tests. lnterictual PET-investigation was acquired 30 rain. after intravenous injection of 185-250 MBq ~SFDG. We applied for neuropsychological testing the testbattery of the helmstaedter working-group (Bonn-Germany). In all cases the PET-findings, a hypometabolic temporal area, correlated well with EEG-localization. In 4/7 patients we revealed a temporal memory deficit with a clear side classification, which correlated significantly with the EEG-and PET-lateralization of the epileptogenic area. In 2/7 cases there were bitemporal neuropsychological deficits. One neuropsychological test was rejected because of both-handing. These results demonstrate, that (1) noninvasive information about epileptogenic brain areas can be gained from 18FDG and PET. (2) If the findings of EEG, PET and neuropsychologieal tests agree referring to the lateralization, this may spare patients a stressful invasive diagnostic by EEG with subdural records. Effective surgical treatment for medically intractable bitemporal epilepsy complex partial seizures depends upon accurate identification of the epileptogenic brain zone. In bitemporal epilepsy (BTE), this remains difficult and requires extensive evaluation by several modalities and invasive depth electrodes. The aim of this study is to evaluate FDG PET findings in the lateralization of BTE in 23 patients (12 women and 11 men) and correlate them with other modalities. The dose for PET was 5-10 mCi of F-18 FIX; (i/v). All patients had interictal F-18 FDG PET scan, MRI, prolonged EEG/video monitoring and invasive depth electrode study. MRI was abnormal in 5 patients, of these only 3 showed lateralization (13%). Scalp prolonged EEG showed definite !ateralization in 2 patients (9%). PET scan revealed lateralization (hypometabolism in one temporal lobe) in 13 patients. In these patients there was agreement in lateralization between PET and Ictal depth electrodes in 11 patients and discordance in 2 patients. In the remaining 10 patients, there was bilateral temporal hypometabolism (non-lateralization) or equivocal PET scan. In this group, ictal depth electrodes findings agree with PET findings (nonlateralization) in seven out of 10 patients. However, there was lateralization by ictal depth electrodes in 3 patients; two patients were shown to have a right temporal focus and underwent a right temporal lobectomy and the third patient showed a left temporal focus. In patients with temporal epilepsy, MRI and scalp EEG prolonged monitoring revealed lateraEzation in a small percentage of patients. In contrast, there was overall concordance between FDG PET and depth EEG findings in 18/23 patients (78%). Manninq, Critchley', C Charlwood, J University Depn of Clinical Chemistry and *Dept of Nuclear Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP. Etidrona~e 400 mg/day glven cyclically 2 weeks out of every 12 weeks for 2-3 years is a recommended nrea~menc for osneoporos~s (Regimen i). In an annempn co improve efficacy, the same dose of etidronate was given but for 8 weeks of each 12 week cycle (Regimen 2] . An open, randomised trial was undertaken to compare Regimens 1 and 2 given for 2 years. 32 patients were randomised to Regimen 1 and 36 patients to Regimen 2. During the etidronatefree period, calcium and vitamin D intake was optimised in both groups. During their second year of treatment, two Regimen 2 patients developed bone pain and lower limb weakness. Radionuclide bone scans suggested metabolic bone disease and iliac crest biopsies confirmed osteomalacia. The trial was terminated and radionuclide bone scans were performed on consenting participants. Bone scans suggested metabolic bone disease in only 1 of 17 patients on Regimen 1 (bone biopsy awaited) compared with 22 of 27 patients on Regimen 2. 16 bone biopsy results are available in Regimen 2 patients to date: 12 show evidence of osteomalacia. The high incidence of osteomalacia makes Regimen 2 an unsuitable treatment regimen. Bone scintigraphy is not routinely performed in osteoporotic patients but it played a vital role in this study in the identification of a serious adverse event. Aim of the study: Diabetic polyneuropathy leads to an alteration in bone perfusion by the opening of arterio-veneous shunts. A relationship between sympatholytic increased bone perfusion and diabetic osteopathy is discussed. Aim of the investigation is to show a possible correlation of bone density, examined by double-photon-absorptiometry (DPA) and the state of diabetic polyneuropathy. Performance: The study includes 60 diabetics and 30 control persons. Diabetic polyneuropathy was found in 30 diabetics. Exclusion criteria were neurological diseases of non-diabetic origin, osteological diseases as well as medications with an effect on the nervous system or on the bone turnover. Bone density was measured in the left femoral neck and in a defined region of the left distal lower leg. Findings: In the diabetic group we found a significantly reduced bone mineral content g/qcm hydroxilapatidequivalent in the area of the femoral neck (0,87 _ 0,17 vs. 0,93 _+ 0,14; p < 0,05) and in the area of the distal lower leg (0,92 + 0,13 vs. 1,01 _+ 0,13; p < 0,01 ). However, no significant difference between diabetics with or without polyneuropathy could be found. Conclus ons There s no correlation between the existence and state of diabetic polyneuropathy and the bone mineral content appointed by DPA. While the whole-body retention values reflect the elevated binding capacity of the bone due the liberation of hydroxyl apatite binding sites the effective half lives indicate the accelerated kinetics of bound 131I-BDP3 as a consequence of the enhanced turnover rate. The faster liberation of radioactivity in patients with OP and PI-IP as well the delayed turnover in PD as compared to the control demonstrates the sensitivity of the method. Measurement s of 13 II.BDP3 kinetics in bone may therefore be useful in the diagnosis and therapy monitoring of metabolic bone disease. Dynamic Tc-HSA (DHSA) scan is used for staging RSD. Its diagnostic value was never established nor compared with bone scan. Based on c l i n i c a l c r i t e r i a , 116 patients were assigned to low, medium or high RSD p r o b a b i l i t y p r i o r to Tc-MDP bone scan and DHSA scan. Clinical c r i t e r i a were used as reference f o r RSD during follow-up. Receiver Operator Characteristic, employed to assess test c r i t e r i a , showed DHSA scan to be more specific (79%) than bone scan (19%) f o r 100% s e n s i t i v i t y of both. Bone scan of the affected part of the body was test negative i f poolphase displayed equal or s l i g h t l y d i f f u s e l y increased a c t i v i t y and i f delayed phase displayed equal a c t i v i t y when compared to the contralateral side. Other bone scan patterns of the affected part of the body with j u x t aa r t i c u l a r y and d i f f u s e l y increased or d i f f u s e l y decreased a c t i v i t y when compared to the contralateral side were test positive. DHSA scan was test positive i f the timea c t i v i t y curve of the affected part of the body displayed a curve grade I -I I or grade I with a countrate r a t i o to the contralateral curve of more than 1.16 at 12 min; other curve patterns were test negative. Bone scan sensit i v i t y was over 97% and s p e c i f i c i t y was below 54% in a l l groups; DHSA scan s e n s i t i v i t y was 81% and s p e c i f i c i t y was over 86%. Diagnostic accuracy of DHSA scan was higher than of bone scan (86% versus 63%) in the low p r o b a b i l i t y group and was similar in the medium p r o b a b i l i t y~r o u p (87% and 85% r e s p e c t i v i l y ) . Performing DHSA scan only in case of a positive bone scan yields a s p e c i f i c i t y and a diagnostic accuracy higher than 89% in a l l groups. Considering the cost of therapy f o r RSD, a specific test is required. DHSA scan, alone or combined with bone scan, may be suitable in this regard. The EM (Expectation-Maximization) algorithm is one of the most employed in iterative SPECT reconstruction because it takes into account the Poisson statistic assumption. Due to the ill-posed nature of tomographie reconstruction, iterative methods cease to converge at a high number of iterations. Therefore, a priori information on the solution must be introduced (so called regularization) to assure the convergence.Various a priori can be used. Gibbs distributions are popular in image processing because they can model many different distributions. We choose one of them which assumes that all neighbouring pixels differences should be smoothed below a defined threshold and preserves above. This provides a regularization which preserved the discontinuities in the image. When regularized and in order to derivate the total energy term, the EM becomes a MAP-EM OSL (Maximum a posteriori-Expectation maximization one step late). ARTUR is an adaptative deterministic relaxation algorithm which relax the Poisson statistic. It models the photon counts by a Gaussian likelihood. We compared MAP-EM OSL and ARTUR, both using such a regularization on numerical and physical phantoms. Our data were acquired for different count rates and the numerical simulations were corrupted with Poisson noise. For the same image quality in terms of Signal to Noise ratio (SNR), at a number of counts in current use in clinical diagnoses, 60 iterations of 10 see were necessary with ARTUR and 250 iterations of 20 sec for the MAP-EM OSL. At a lower count rate the same result need 120 iterations for ARTUR and 250 iterations for the MAP-EM OSL. These results show that if the performances of both algorithms are equal, even at low count rates, computation time make a consequent difference in favour of ARTUR. YW Bahk, YH Park, SH Kim, SK Chang Depts of Radiology and Nuclear Medicine, Catholic University Medical College, Seoul, 137 KOREA PINHOLE BONE SCAN SIGN OF CHONDROMALACIA PATELLAE Chondromalacia patellae (CP), pathologically characterized by a series of degenerative changes in the retropatellar cartilage, is one of the most common causes of anterior knee pain. Its primary diagnostic approach is radiography augmented with arthrography. But radiography is gradually becoming replaced by arthroscopy, CT and MRI, which are either invasive, expensive or not readily available. Technetium-99m MDP/I-IDP bone scan is a well established adjunct in the study of bone and joint diseases, and recently pinhole scintigraphy (PS) has been shown to provide important and often pathognomonic information. In the present communication we wish to describe a hitherto undescribed scan sign of CP as revealed by PS. The scan changes were prospectively analyzed in 10 patients with CP, and findings were compared with those of osteoarthritis, rheumatoid arthritis and Reiter's syndrome. In all four disease groups studied the planar bone scans showed simple "hot patella" sign that has no distinguishing feature. But, interestingly enough PS portrayed in all ten CP cases a characteristic spotty tracer uptake that was localized in the central retropatellar facet. In contrast, in 12 (75%) of 16 cases of osteoarthritis, rheumatoid arthritis and Reiter's syndrome PS showed increased patellar uptake to be not localized but diffused in the retropatellar facet. The uptake was spotty in the remaining 4 cases, but none of these were in the central facet. Small spotty tracer uptake localized in the central retropatellar facet is pathognomonic of CP. The purpose of this study was to simplify the detection of brain lesions applying a standard stereotaxic coordinate system. The automated comparison of brain studies with a normal anatomical and functional database requires transformation of a 3D image into a standardised coordinate system. Conversion to the stereetaxic Talairach arias (1988) was obtained after identification of the mid-sagittal plane, the bicommissural line (ACPC) and the brain surface contour. Following activity nornmlisation, a "mean-activity-map" and a "vuriance-activity-map" of the brain was computed. Mid-sagittal plane localisation was done by a registration procedure where the left hemisphere is compared with the right hemisphere and vice versa. Three landmarks -a frontal, an occipital and a sub-thalamic pointwere detected in the mid-sagittal plane to extract the ACPC-plane. A 3D segmentation procedure was applied to determine the brain contour. Activity normalisation was achieved by computing the modus of the ratio obtained by dividing the reference image data with the patient image. Afterwards, the anatomical ROls, based on the Talairach co-ordinate system, could be created. Moreover, a map of the significant differences from the functional normal database ( 28 patients ) was generated. In a series of 24 patients (10 CVA's, 8 TIA's and 6 normals) the transformation had to be corrected manually in 5 cases (1 half-brain CVA, 1 thalamic CVA, 1 image with low signal-noise ratio and 2 probable movements during acquisition). There was a significant difference between the pathological and the normal patients using the mean count ratio between the suspected region and the cerebellum (p=0.01) or the contra-lateral region (p=0.008) as a reference. These results suggest that this program cart objectively and reproducibly detect and quantify brain lesions in 80% of the cases. Institute of Medicine, Research Centre Jtilich and Department of Nuclear Medicine, Heinrich-Heine-University Diisseldorf, Jtilich, Germany A WIENER RESTORATION FILTER FOR ITERATIVELY RECONSTRUCTED O 15-BUTANOL-RCBF-IMAGES Restoration filters which usually employ the sp~.cific system modular transfer function (MTF) improve the contrast of small structures and reduce high frequency noise simultaneously. This study applies an individualWiener restoration filter (WRF) to iteratively reconstructed O15-butanol-images in dynamic studies exhibiting low count-statistics and insufficient resolution which is in part caused-by the long positron range of Ot5 (positron energy 1.7 Me'V). To circumvent the difficulties of generating the MTF for the ultra short-life isotope O15, we used Tc94m (T~/z =52 rain) with a positron energy of 2.5 MeV and compared it to F18 (0.6 MeV). Count dependent signal (S(f)) and noise (N(f)) spectra were determined and f.ttted using a 2D-Hoffman brain phantom filled with Tc94m. Based on tl~ese ~ data, we designed a WRF described by: Because of rotational symmetry of the frequency spectrum, the filter function was calculated one-dimensionally and applied to the low count-images of the Hoffman phantom and of O[5-brain-activity in patients in the frequency space two-dimensionally ( In conclusion, we designed a Wiener restoration filter based on an isotope specific MTF for O15 ~CBF studies, which improves resolution and quantitative tracer recovery in brain activation studies. Most clinical demonstrations with factor analysis of image sequences reported until today can be charaeterised as feasibility studies rather than rigorous clinical trials. Considering the complexity of diagnostic problems attempted to be solved by factor analysis~ it is surprising that basic quantitative dependences of extracted factors on the temporal and spatial sampling of input data are still not known. The aim of this study is to partially fill the ~ gap. Six high-frequency MAGS renal studies (300-400 images 64x64x2 recorded in 3-second intervals during 15-20 minutes in total) have been collected and analyzed using a workstation and an automatic procedure of factor analysis. Oblique rotation of factors was performed in the spatial domain and a Bayesian procedure used to automatically control the rotation. Using this method, the data have been analysed repeatedly while varying input conditions systematically in wide limits. The h~'pothesis was that the extracted factors (dynamic structures, compartments) should be invariant since the input data reflect the structure and function of real compartments inside the body sufficiently accurately. The parameters investigated were the time interval and region of interest to be used in the analysis, the effect of smoothing, the reduction in temporal and/or spatial sampling, and the number of factors. The results confirmed the hypothesis over a wide range of input parameters. When comparing the factor curves with the corresponding curves obtained from standard ROIs the main difference roland was that the factor curves approached zero at the same time when the factor structures lost their contrast against background. The conclusion is that the reproducibility of factors confirm both their usefulness in clinical studies and their p}rysiological meaning. Addi~ tional facts produced by the experiment help to understand the interpretation of factors~ predict their ap~ pearance, and formulate more accurate advice for users. Carbon-t1 L-159,884, is a radiolabeled antagonist of the angiotensin II/AT1 (AT1) receptors. The purpose of this work was to investigate the binding properties of this new PET agent using the renal impulse response function. Carbon-ll L-159,884 was injected to three dogs under pentobarbital anesthesia before (4.30+0.46 mCi, 3624+ 1657 mCi/gmole) and after (4.46-+0.67 mCi, 2699_+1450 mCi/~tmole) pretreatment with t mg/kg of MK-996, another potent antagonist of the ATt receptors. A dynamic PET stud3, was performed over 105 minutes. The input function was obtained from metabolite corrected plasma samples. The impulse response function (IRF) obtained by model-free deconvolution demonstrated three distinct components corresponding to vascular activity, non-specific binding, and specific binding. An average value of the third component (IRF60-105) was calculated 60-105 min. p.i.. Using the compartmental model the following parameters were calculated by the Marquardt algorithna: kl and k2 (tissue uptake and release) k3 (specific binding), as well as k3/k4 (binding potential). AT1 blockade reduced the specific binding of the tracer by ~80% measured both by the binding potential (k3/k4) and the model-free IRF (Table) . Thus, [C-11] Fractal compression is a newmethod for image data encoding which competes with traditional transform coding. The Banach fixed point theory had given ef%ective tools for the design of fast image reconstruction algorithm. We used ,,local patchwork" approach,based on 4x4 pixel blocks in order to establish the best fit local transformation of image blocks. We applied fractal method for compression of scintigraphic images.We analysed 37 liver and 22 boos scintigrams (byte mode aquisition,128x128 matrix size) before compression -group I and after reconstruction of these compressed images -group II.lhe program was written in C.The reduction of image data size, we have obtained, was between 7 and 12 times as a function of local search radius, chosen of affine transformations group and entropy efficiency.For optionally selected regions of interest (ROI-s 32x32 and 64x64) we found that the total number of counts for regions in scintigrams from group II was slightly higher than in regions from group I.The increase number of counts ranged from 0.017% to 0.26% for ROI-s 32x32 and from 0.0~% to 0.7% for ROI-s 64x6~ (the regions of interest 64x64 included areas outside of the organ). The images from group II were smoothed and appeared better (sub3ective measure!) than original images.The fractal smoothing may be used as a separate option. In conclusion,the fractal compression of scintigrams is useful because of disk space saving and the reduction of transmission time by about 90~.Decompresion of images does no'~ a$~ecf significantly their quality but their smoothing improves the visual perception. G. Fedders 1, R. Bares 2, D. Rohde 3, R. Kock 1, G. Jakse 3, U. BueU 2, H. ~1 Departments of Clinical Chemistry 1, Nuclear Medicine 2, and Urology 3, Technical University of Aachen, GERMANY During the past decade fluorine-18 labelled 2-fluoro-2-deoxy-Dglucose (FDG) has been frequently used for in-vivo assessment of glucose metabolism by positron-emission-tomography (PET). Assuming that metabolization of phophorylated FDG is slow and therefore neglegible within the first 2 hours after injection, the distribution ofF-18 measured by PET is usually regarded to reflect the local amount of phosphorylated FDG. The aim of our study was to check this assumption using human prostate cancer cells as model (LnCap-well differentiated/PC3-1ess differentiated). After serial incubation of culture plates with C-14 labelled FDG or 2-deoxy-Dglucose (DG) the time course of cellular FDG/DG accumulation was measured, and intracellular metabolites were identified by HPLC. Thirty minutes after incubation significant quantities of FDG-6-P and FDG-1-P, and after 2 hours also UDP-FDG, UDP-FDGal, and FDGluconate-6-P were detected. In LnCap cells FDG-6-P increased constantly for 4 hours while in PC3 cells an early maximum was reached after 60 minutes. DG-turnover was considerably faster compared to FDG, the main products were DG-6-P and DGluconate-6-P. The results indicate that metabolic pathways of cancer cells are highly variable which may cause underestimation of glucose metabolism if quantification is exclusively based upon static PET-scans. The observed differences between LnCap and PC3 cells can be explained by limitations of substrate transport (PC3) emphasizing the relevance of transport mechanisms (e.g. expression of glucose transporter proteins) in addition to enzyme activities. Thus, for accurate estimation of tissue metabolism dynamic PET scanning is required. Thallium still remains unbeatable isotope for myocardial perfusion scintigraphy, particularly for the diagnosis of myocardial viability, and gains new oncological applications. Newertheless, its long physical and biological halt-life times as well as high radiation dose make impossible the usage of this isotope for frequent tbllow-up studies and control of myocardial perfusion under surgical or medical treatment. Thus we have developed a technique for low-energy cyclotron production of Thallium-199 chloride (T1/2=7.4hr), compared its technological parameters with Thallium-201 and tested biokinetics and dosimetry of the short-living radionuclide. Thallium-199 has been produced by Au ( He, 2n) T1-199 reaction using We conclude that Thallium-199, which gives equivalent clinical information to that of TI-201, has more reIiable technoeconomic characteristics and provides lower radiation doses, and so makes possible repeat follow-up myocardial perfusion studies with physiological tracer, The aim of the study was an evaluation of serum osteocalein (GLA) determinations in the diagnosis of osteoporosis (OP). The study was performed on the random sample of 653 individuals of Szczecin population (341 women, 312 men), age 40-80 yrs. GLA was measured by RIA using incstar Corporations kits (normal range: 4.2±1.8 ng/ml, Two X-ray pictures of both thoracic and lumbar spine were taken in the lateral position in all examined subjects and evaluated for OP. The diagnosis of OF was based on the following radiological criteria: i) rarefaction of bone structure appearance of strations on the vertebra, 2) intracorpora intussepsception of upper of both limiting membranes of vertebrae, 3) wedge-shape, compression or biconcave deformities of vertebrae. OP was diagnosed in 193 women (56.6Z) and 105 men (33.7%) and the prevalence was parallel to the age of subjects in both sexes. Serum GLA was significantly higher in women than in men (3.7±1.9 ng/ml vs 3.3±1.6 ng/ml, p<0.005). Women with OP had slightly higher GLA than women without OP (3.8±1.8 ng/ml vs 3.5±2 ng/ml, n.s.) but in the subgroup of women in perimenopausal period (45-55 yrs) GLA was significantly higher in women with OP than without 'OP (p<005). The latter was similar in men: GLA was elevated in men with OP when compared without OP (3.7±1.8 ng/ml vs 3.1±1.5 ng/ml, p<0.005). In conclusion, serum GLA determinations may be useful in screening evaluation of bone remodelling in osteoporotic individuals, especially in men and perimenopausal women with diagnosis of OP. Three RIA's for the determination of IGF-I were compared analytically and cli~ically: IGF-I Nichols Institute (NICH), SM-C-RIA-CT Medgenix Diagnostics (I'9[) and IGF-I Mediagnost GmBH (~). NICH (double antibody liquid RIA) was performed without any extraction in order to obtain only free IGF-I. The procedure includes a predilution, 6 pipetting steps, an overnight incubation and a centrifugation/aspiration step. MX and ME) determine as well free as bound IGF-I, MX by an acid-ethanol extraction and MD by blocking IGF-I binding sites by IGF-II. MX (coated tube RIA) needs 4 pi~etting and 1 centr, step for the acid-ethanol extractlon, an overnight incub, and one wash cycle. FD (double AB liq. RIA) uses an acidic dilution, 3 plpetting steps and a 2 days+lhr incub.. The centr./asp. step has to be performed 2x to obtain better precision. Data reduction was performed with linear smoothed spline. Curve fitting performance for NICH and MX revealed no problems (iterations I, variance ratio 0) . For ~D curve fitting was bad (it.4, vr.ll.4). For NICH 100% (30/30) of the patient sanloles (duplicates) had a within-assay precision (CV) <10%, for MX and MD resp. 91.7% (33/36) and 90.6% (29/32) of the results had CV's = 5,5 + 4,1 years). The renal scan was performed 2 hours after the injection of a weight related dose of Tc-99m DMSA, with a 256x256 matrix and an acquisition time of 180 seconds, under 3 projections (posterior; left and right posterior obliques). Results obtained with the 3 projections and with the posterior projection alone were compared. US was performed on the same day, using a 3,5 MHz transducer. Four US criteria were tested: irregular cortical margin, cortical thinning, focal calyceal dilatation and hyperechoic cortical loci. 62 RS in 46 renal units were detected by the 3 projection DMSA scan. 23 of them corresponded to normal US studies; 14 (23%) had l positive criterium (focal calyceal dilatation was the most frequent); 14 (23%) had 2; 8 (13%) had 3 and 3 (4%) had 4. Cortical thinning (28%), irregular cortical contour (27%) and focal culyceal dilatation (26%) were the criteria most frequently found. The posterior projection of the DMSA scan alone revealed 48 RS (77%). The average number of positive US criteria per RS was !,3. If we consider US studies with 2 or more positive criteria (above the average) as being suspect of RS, we find that only 40% of the US studies would be classified as abnormal. Although calyeeal dilatation was the most common finding when only 1 positive crlterium was present, it was not the most frequent when the whole group was considered. We conclude that US, besides having an already known low sensitivity in detecting RS, does not even have a reliable pattern of findings that allows the establishment of levels of suspicion. Renal DMSA scan in only 1 projection (posterior) was still far better than US (77% of ItS detected). The introduction of new mefi~ods for biochemical parameters of bone related processes necessitates reevaluation of the diagnostic regimen in bone metastases. We present a study initiated by the question whether the new radioimmanological test for bone specific alkaline phosphatase (BAP) yields additional or more adequate information than routine bone scintigraphy in patients with breast or prostatic cancer. For 130 post-operative patients (95 breast and 35 prostatic cancer) the results of two different methods for the determination of BAP were compared: photometric determination after wheat germ precipitation (Boehtinger Mannheim) and two site immunoradiometric assay COstase", Hybritech). Bone scans were recorded simultaneously (99mTc-HlvlDP, whole body scanning, anterior and posterior ,dev,,s, Siemens-Bodyscan). Patients with bone lesions were X rayed and followed-up for one year. Results: 62 patients were free of any scintigraphic lesions, 29 had increased focal activity accumulation caused by degenerative processes and 39 patients had lesions caused by. solitary or multiple metastases. The information content of the biochemical tests was determined using ROC diagrams. With a 90 % specificity both tests had a sensitivity of 60 %. The results of both determinations showed a significant correlation (r = 0.85, p< 0,01). The optimal threshold for differentiating patients with and without metastatic disease was found to be 25 ng/ml for the immanoradiomemc assay. We conclude that both methods of BAP determination provide similar results and that neither method offers the potential to substitute bone scintigrapby in primary diagnosis of metastatic disease, due to limited accuracy. The role in therapy remains to be defined. Tc-99m-MAG3 scan allows a good renal imaging in neonates and provides a lower dose than Tc-99m-DMSA. Aim of the study is to verify the clinical usefulness of MAG3 scan in evaluating the renal damage in babies with congenital V U R before the onset of upper tract infections (UTI (APN) . Infants less than 24 months old are a special interest group due to a higher probability of kidney damage during an urinary tract infection, and to a relatively high incidence of APN. This study tries to increase our knowledge about the evolution of the acute pyelonephritis in these young children. DMSA scans performed in 29 children during the APN and 12 months after have been analyzed (persistence, improvement or normalization of the hypoactive area(s), variation in differential function, grade of vesico-ureteric reflux). Experimental partial ureteral obstruction can lead to reduced GFR in the weeks following surgery, the intensity of this reduction being dependent on the severity of the stenosis. After this transitory period, the function remains stable, suggesting that patients with congenital hydronephrosis (HN) are not at high risk of further degradation of the function. Similarly, it is logical to think that a preserved function, in a patient with congenital HN, is not suggestive for marked obstruction and one might therefore expect a good renal emptying after furosemide.The aim of the present work was to evaluate if a normal GFR on the site of the affected kidney can predict a good response to furosemide. During the last 4 years, we performed 348 Tc-99m MAG3 pediatric studies because of HN or vesico-ureteral reflux (VUR). The separate GFR (SGFR) was estimated by combining the left to right MAG3 early renal uptake and the overall GFR obtained with Cr-51 EDTA. The response to furosemide was evaluated quantitatively by measuring the residual renal activity (RA) in percentage of the pre-furosemide value. Among the 348 studies, 202 were not followed by a furosemide test, either because the drainage was already satisfactory at the end of the 20 minute renographic study, or because the main purpose of the examination was the detection of VUR by means of indirect cystography. Among the 146 studies (291 kidneys) completed by a furosemide challenge, 139 corresponded to unilateral HN and 7 to bilateral HN. SGFR was considered as normal in 92 kidneys and abnormal in 61. In the group with normal SGFR (age between 1 month and 12 yrs), 90/92 kidneys showed good renal emptying after furosemide (highest RA 40%). In the group with abnormal SGFR (age between 1 month and 20 yrs), the RA after furosemide was less than 40% in 47 kidneys, between 40 and 60% in 7 kidneys and, in the rermaining 7, more than 60% corresponding to poor emptying. In conclusion, a normal SGFR is highly predictive for a good response to furosemide. It has been suggested that children over 5 years of age with a first documented urinary tract infection (UTI) are unlikely to develop renal lesions and therefore do not require scintigraphic investigations in case of normal renal ultrasound. The aim of the present work was to evaluate, in this category of patients, the frequency of the scintigraphic abnormalities. Ninety-one children older than 5 years were found in a database of 261 patients who underwent, between January 1991 and December 1992, DMSA scintigraphy for suspected UTI. The clinical files of those children were closely examined by two experienced paediatricians. Patients with incomplete file data, a history of previous UTI, known obstructive or reflux uropathy were excluded. Twenty-three patients remained who underwent both renal ultrasound and DMSA scintigrapby during the acute phase of a first culture-documented febrile UTI. Among these 23 patients, cortical defects were found on DMSA scintigraphy in 14 children (61%). Follow-up scintigraphy, performed 2 to 12 months after the first one, revealed, in 7 children complete healing or considerable improvement of the defects, confirming that the UTI affected a previously normal kidney. In 4 patients, a small deformed kidney, obviously existing, but unsuspected before the present UTI, was detected on the first scintigraphy and the lesions remained unchanged on follow-up scan. One child developed new lesions due to a second episode of pyelonephritis. Two children with focal renal lesions on DMSA scan had no follow-up scan. Renal ultrasound examination was entirely normal in the 9 patients with normal DMSA images but also in 6 out of the 14 patients showing scintigraphic abnormalities. In conclusion, although the incidence of a first UTI is low in children older than 5 years, the frequency of scintigraphic abnormalities is comparable to what is found in younger age groups; part of them are clearly related to the current infection. In this age group, a strategy based exclusively on ultrasound examination would miss a significant amount of abnormal kidneys. The aim of this study was to determine i f the renal function established by renography with 1-123 hippuran within the f i r s t three months of l i f e was of any prognostic value in children with urinary tract dilatation detected prenatally. We have studied 51 children (39 boys, 12 girls) with dilatation of 72 renal units. A total of 180 studies were performed, starting 4-110 (mean 36) d after birth and followed up to 5y. 5 studies (34) were excluded because of incomplete injection. 16 presented unilateral (10) or bilateral (6) The aim of the study was m examine the ability of the simultaneous assessment of left ventricular function and myocardial perfusion using one single injection of Tc99m Sestamibi, to identify high risk patients with left main, proximal LAD and three-vessel coronary artery disease (CAD) after an uncomplicated acute myocardial infarction (AMI). Combined first-pass radionuclide angiocardiography (RNA) and myocardial perfusion SPECT at rest and during submaximal exercise were performed in 52 patients, less than 6 weeks after an uncomplicated AMI, using Tc99m Sestamibi. Patients were classified in two subgroups according to the presence of left main, proximal LAD or three-vessel CAD. Stepwise logistic regression analysis was used to determine the independent predictors of severe CAD. All patients underwent the exercise testing without any medical complication. On multivariant analysis the wall motion score during exercise was the only independent predictor for the presence of severe CAD (p< 0.001, r= 0.6). Analyzing patients with anterior AMI separately, LV EF at submaximal exercise was the most accurate predictive parameter. If a cut-off value of 40% is chosen, the LV EF at exercise had a sensitivity of 85% and a specificity of 78% for the detection of severe CAD. In patients with inferior AMI, LV EF, wall motion nor myocardial perfusion scores were useful to differentiate the two subgroups. In these patients the presence of an additional perfusion defect in one of the anterior wall segments yielded a sensitivity of 70% and a specificity of 75% for the presence of severe CAD. In conclusion, simultaneous evaluation of LV function and myocardial perfusion at submaximal exercise, using one single injection of Tc99m-Sestamibi, is a safe and accurate technique to select patients with severe CAD after an uncomplicated AMI. In patients with anterior AMI the best parameter for selection is the global LV EF at exercise. In patients with inferior AMI an additional perfusien defect in the noninfarcted anterior wall yields the highest predictive accuracy. The purpose of this study was to evaluate the accuracy of adenosine Tc-99m sestamibi SPECT in the detection of jeopardized myocardium early after acute myocardial infarction, Coronary arteriography and myocardial scintigraphy were performed early after myocardial infarction in 41 consecutive patients with an unco~olieated myocardial infarction. Tc-99m sestamibi SPECT was performed both at rest and after IV adenosine infusion (140 ~g/kg/min during 6 min, in 40 ml saline). The SPECT-images were analyzed semiquantitatively using a 17 segment model. A reversible perfusion defect in the infarct region occured in 23 patients (56 %) and was almost solely observed in the presence of jeopardized myocardium [Myocardium was considered jeopardized if the successfully reperfused infarct region was supplied by a residual significant coronary artery stenosis (> 50 %). Jeopardized myocardium was present in 24 (58 %) patients]. Adenosine Tc-99m sestamibi sPECT had a sensitivity of 87%, a specificity of 88% and a accuracy of 88% for the detection of jeopardized myocardium. Adenosine Tc-99m sestamibi SPECT correctly identified 100% (20/20) of patients with single vessel disease, and 75% (12/16) of patients with multivessel disease. These results suggest that adenosine Tc-99m sestamibi SPECT is a fairly accurate non-invasive method for detecting jeopardized myocardium and may be a valuable non-invasive test for the early selection of high risk patients surviving acute myocardial infarction. Depts. of Nuclear Medicine and 1internal Medicine III, University of Cologne, 2MpI for Neurological Research, Cologne, Germany To assess residual viable myocardium, 40 patients with chronic myocardial infarction (infarct age >_4 months) and regional akinesia or dyskinesia by ventriculography underwent 18-FDG positron emission tomography (PET) after oral glucose load and transesophageal echocardiography (TEE) at rest and during lowdose dobutamine infusion (5, 10 pg/kg/min). A standardised 26segment model consisting of 3 short axis tomograms and a transverse midventricular long axis tomogram was used for analysis of FDG-uptake and wall motion in corresponding myocardial regions. Segments with an FDG-uptake >_50% of the maximum FDG-uptake and with a dobutamine induced wall motion were graded viable by PET and TEE, respectively. PET diagnosed residual viability within the infarct region in 25/40 (63%), TEE in 21/40 (53%) patients. Diagnostic agreements between the 2 techniques was 90%. 235 of totally analysed 1040 segments were akinetic or dyskinetic by TEE at rest. Within these 235 segments myocardial viability was graded concordantly by PET and TEE in 89% of segments. Compared to FDG-PET defined viability, positive predictive accuracy of dobutamine-TEE was 81% and negative predictive accuracy 97%. FDG-uptake in segments with a dobutamine induced contraction reserve (68+11%) was significantly higher (p=0.001) compared to segments remaining akinetic or dyskinetic during dobutamine infusion (45:1:9%). Compared to the "gold standard" FDG-PET, dobutamine-TEE yields a good correspondence. Like reinjection or resting scintigraphy with 201-TI, dobutamine-TEE may offer an alternative to FDG-PET for the assessment of infarct region related myocardial viability. To determine whether a patent coronary artery correlates with restoration of myocardial tissue perfusion after successful thromboiysis, blood flow (BF) measurements using 13N-NH3 were performed in 11 patients (pts) within 24 hrs after onset of infarction. All patients received thrombolytic therapy within 4 hrs after onset of symptoms. Coronary angiography was performed at 90 rain and at 5 days. Only pts with a TIMI-3 grade patency at 90 minutes were selected. Patients underwent a control flow (N-13 NH3) and metabolic (F-18 FDG) study 5 days and 3 months later. In 8 out of 11 pts, only a moderate decrease of BF was found initially (71+8 ml/min/100g) of whom 5 showed preservation of BF (73+9 ml/min/100g) and metabolism during follow-up, in 1 patient PTCA was performed because of a mismatch pattern at 5 days resulting in improvement of BF and metabolism. In 2 pts, a decrease of BF (35+9 ml/min/100g) and metabolism was found at 5 days of whom 1 showed reocclusion. On the contrary, in 3 out of 11 pts, a severe reduction of BF (31+7 ml/min/100g) was present in the acute stage although the infarct related coronary artery was patent. Control studies in 2 of those 3 pts showed persistently reduced BF (32+6 ml/min/100g) and metabolism compatible with necrosis. Having a mismatch pattern at 5 days, and a critical stenosis, the third patient underwent a PTCA resulting in a restoration of BF (69 ml/min/100g) and metabolism measured after 3 months. We conclude that persistent flow after thrombolytic therapy, as shown by acute coronary angiography, is not always associated with optimal tissue perfusion. In patients showing 'no reflow' at 24 hrs, flow/metabolic PET studies are helpful to identify viable tissue. Tomoscintigraphy of myocardial parenchyma is highly sensitive but poorly specific as to the detection of infarction. We have compared the usefulness of gated tomography of the heart cavities (4D-angio) to that of Tc-MIBI tomography (tomo-MIBl) for that condition. Both investigations were performed at 2-day intervals in 80 patients (acute infarction (50%), heart failure, angina, dyspnea and valvulopathy). 4Dangio was performed after in vivo labelling of red blood ceils with about 1300 Mbq of Tc-pertectmetate. Acquisition was obtained using a 3-head camera (TRIAD) in about 15 minutes. Image treatment was done by automatic segmentation in 4 cavity dimensions. Contraction amplitude was obtained by the "slope method", whereas zones with abnormal phase were identified by comparison with a normal population and the lesions being shown in a Bullseye projection. Only those zones showing concordant pathology in phase and in amplitude were considered positive. Tomography of the parenchyma was obtained 60 rain. after injection of 740 MBq of Tc-MIBI and comparison with a normal population (CEQUAL program) was projected as Bullseye. For each test, the lesions fom~d were compared both visually and quantitatively (extent, depth, arterial territory). The existence of a history of infarction was based on clinical data, chemical results and ECG. Results: Tom0-MIBI 4D-ANGIO + + lnfarcti [ + 37 3 26 14 I on 28 12 6 34 4D-angio appears as less sensitive but much more specific than tomo-MIBI, and its accuracy is higher (75% vs 61%). False negatives are mainly small inferior infarction, whereas the false positives in Tomo-MIBI were mainly due to attenuation problems. In the conditions of oar study, 4D-angio appears as highly superior to tomo-MIBI for the detection of myocardial infarction. In-lll-PENTETREOTIDE, Tc-99m (V)-DMSA AND 1-123-mIBG The aim of the study was to reveal primary and/or secondary foci that are clinically occult in suspected, positive for somatostatin -receptors tumours, and to evaluate their tumouricidal behavior. Among 38 patients (a) 4 (all females aged 38 to 51 years) suffered from medullary thyroid carcinoma, (b) 6 (2 females and 4 males aged 41 to 57 years) had small-cell lung carcinoma, (c) 11 (6 females and 5 males, aged 8 to 46 years) had pheochromocytoma, and (d) (5mCi) In-111-Pentetreotide to each patient with pheocbromocytoma, breast and small cell lung cancer (3-4 days time interval between the two examinations). Tc-99m (V)-DMSA scintigraphy was carried out 2.5 and 5 hrs, In-lll-Pentetreotidc static images 5 and 18 hrs and 1-123-mlBG scans 24 and 48 hrs (delayed scans for comparison) after i.v, application. Tc-99m (V)-DMSA 4/4 2/6 12/17 3/11 In-ll 1-Pentetreotide 3/4 6/6 17/17 9/11 1-123-mlBG 2/4 2/6 6/17 10/i1 According to the results we can conclude: (a) all three radiopharmaceuticals showed higher sensitivity than do conventional imaging techniques, (b) medullary carcinoma showed in all cases a positive Tc-99m (V)-DMSA scan, small cell lung carcinoma and breast cancer a positive in all cases In-111-Pcntctreotide scan, while an interesting accumulation in APUDomas and breast cancer was observed; (c) it is worthwhile to be noticed that the general sensitivity and specificity for all three radiopharmaceulicals is high; (d) the examinations are easy to performe and safe. Because the schedule of early investigation in acute myocardial infarction (MI) is critical, a realistic strategy for the assessment of the infarcted area with In-111 antimyosin-antibody (AM) would imply an immediate injection of cold AM in intensive care unit. Then tracer administration and imaging could be delayed after emergency therapy. Moreover, suoh a two-step targeting could improve the signal to noise ratio, since liver uptake is critical. The streptavidine (Sav)-biotine (B) system is interesting because of the high affinity binding of B to Sav, and the small size of the labelled tigand. The myocardial uptake (autoradiography), the biodistribution, and the image quality of two different AM were evaluated: In-111-DTPA-Fab (Myoseint, Centocor), and two-step Fab'2-Sav followed by In-111-DTPA-B. A MI was induced in 25 male rats by left descending coronary artery tying. 24 h after surgery, 15 rats were injected with Myoscint (G1, 10 _+ 1 pg), and 10 rats with the conjugated Fab' 2 (G2, 11 _+ 2 IJg), followed by In-111-B injection 24 h later. Anterior 5 minutes-images were acquired at 6, 12, 24, 48 h on a gamma camera with a pin-hole collimator. Biodistribution and autoradiography were performed at the same times. Results. A better delineation of the infarcted area was obtained on images of G2 since the liver was not visualized. The specificity of myocardial uptake in the infarcted area was confirmed by quantitative autoradiographic data. In G2, the counts in normal myocardial area were not significantly different than noise. The best blood to myocardial ratio was obtained at 48 h of the tracer injection for G1 and at 12 h for G2 (0.52 _+ 0.05 vs 0.49 + 0.07, ns). Although absolute myocardial uptake was 8.2 times lower in G2 vs G1, noise was 55 times lower resulting in an increase of 6.9 times in the signal / noise (heart / liver) ratio for the conjugated AM (0.19 +0.02 in G1 vs 1.31 _+0.2 in G2, p<0.0001). Conclusion: two-step targeting of infarction with AM and Sav-B system allows delayed injection of the tracer and imaging, which is crucial in this clinical situation, and improves image quality. To predict the success of octreotide treatment from endocrine active pituitary adenomas a method for semiquantitative determination of somatostatin receptors with In-111-pentetreotide was developed. 15 patients were examined suffering from pituitary adenomas confirmed by clinical and lab examinations, MRI and histology. The reference group contains 13 patients suffering from medullary thyroid carcinoma which received additionally a In-lll-pentetreotide-SPECT-Scan of the head and neck area, SPECT studies (60 s / frame, 64 frames at a 64x64 matrix) were accomplished 4 and 24 h after i.v. injection of 220 MBq I n -l l lpentetreotide using a dual head camera equipped with medium energy collimators (FWHM = 15 mm). After reconstruction with a Butterworth filter (8/0.34) an attenuation correction using the CHANG-algorithm was performed. Coronal scans were obtained after reconstruction and the slice containing the count maximum of the pituitary gland was selected. A "pituitary uptake index" was built from the ratio of the count maximum in the pituitary gland and neighbouring skull bone at 4 and 24 h p.i. The results show an increase of the uptake index from 4 to 24 h in the adenomas and also in the reference group. This increase was 2-3 times higher as an average for the adenomas and shows the stronger binding and density of receptors in adenomas. Of course a clear seperation from the reference group was only possible for adenomas greater than 15 mm in diameter. These results suggest that a estimation of the "pituitary uptake index" could be a useful parameter for receptor density and might be a possibility to predict clinical response on octreotide treatment. R. Lebtahi, L. Sarda, G. Cadiot, M. Faraggi, E de Kerviler, D. Daou, MC. Peker, M. Mignon, D. Le Guludec. Depts of Nuclear Medicine and Gastro-Enterology, H6pital Bichat, Paris, France. Therapeutical management of patients (pts) with endocrine gastroenteropancreaiic tumors (GEP) is dependent on staging. Scintigraphy with Somatostatin analogs is a sensitive method for the detection of GEP tumors and their metastases. The aim of this study was to evaluate the conti'ibubon of 1111n-Octreoscan Somatostatin Receptor Scintigraphy (SRS) in the detection of bone metastases compared to conventional bone scintigraphy with Tc-99m-HMDP. 23 patients (pts) with proven GEP tumors were investigated. HMDP hot spots were classified in metastatic (69 sites, 10 pts) and non metastatic lesions (11 sites, 3 pts) according to RX, CT, MRI, and histological data. Scans were normal with both bacers in 10 pts. For the 11 HMDP hot spots corresponding to degenerative bone disease (n=6) or fractures (n=5), SMS was always negative. HMDP demons~'ated 69 bone metastases (10 pts). SRS was positive in 9 / 10 pts. The last pt had a non-secreting GEP. 23 Iocalizations were missed with SMS. In 1 pt, 4 right ribs metastases were hidden by the superimposition of an high uptake in liver metastases. Conversely, SRS revealed 44 others previously unknown bone metastases, associated to a diffuse axial squeletal bone involvement in 4 pts. This extensive involvement was confirmed by the osteo-medullar biopsy (1 pt) or by HMDP performed 6 months later (2 pts). These preliminary results suggest that SRS seems specific and provides additional informetions in bone metastases detection of GEP tumors. Further studies are needed to confirm the eadier detection of bone metastases by SRS compared with HMDP. M~q; 300 pmol). I~3I-VIP was initially bound by the lungs, whereas no tracer accumulation was observed in the bowel. Elemination occured via the kidneys. ~23I-VIP provided excellent visualization of adenocarcinomas, carcinoids, insulinomas, lymphomas and of metastases spread from melanomas. Binding of 123I-VIP by primary tumors as well as by liver-, lung-and lymph node-metastases was visible shortly after injection of 123I-VIP and was still demonstrable at 24 hours. Tumors of 0.5-1 cm in size were visualized. Primary adenocarcinomas, carcinoids, insulinomas and intestinal lymphomas were imaged in 90%, whereas only 20% of hypophyseal adenomas were visualized. In 60 patients comparative studies were performed with 1~tIn-DTPA-Phe-l-octreotide or 1~31-Tyr-3-octreotide demonstrating that 123I-VIP maintains a higher sensitivity for adenocarcinomas and some endocrine-related tumors. We conclude that 123I-VIP receptor scanning provides a novel and potent technique for the visualization of ~23I-VIP expressing tumors. The influence of a somatostatintherapy on the scintigraphic result with In-111 -octreotide was prospectively examined in 6 patients with different neuroendocrine tumours( carcinoids n=3; metastatic pheochromocytoma n=l ; metastatic paraglioma n=l ; not specified neuroendocrine tumor n=l). The somatostatin therapy was administered with increasing dose over more than two weeks before In-111 octreotide scintigraphy(3x150ug; 3x300ug; continuous infusion of 1.5mg or 3mg via a pump). 100-185 MBq In-111 -octreotide were injected for scintigraphy. Gammacamera images were aquired as anterior and posterior whole body scans 4h and 24h p.i. The calculation of the tumor uptake ratio in % of whole body activity and the target/background ratio was performed with the ROI-technique 24h p.i. The relative tumor uptake in primary tumours and metastases increased with increasing somatostatin dose (basal:2%+/-0.5%; 1.5mg :3%+/-1.1%; 3mg:4.9%+/-2.3%). The target/background ratio increased under low dose of somatostatin and decreased with increasing dose. A continuous infusion of 3mg somatostatin completely blocked the receptors. In conclusion, a low dose somatostatin therapy(3x150mg) increases the detectability of tum0urs and metastasis and has not to be stopped before scintigraphy. Competetive mechanisms or higher somatostatin receptor expression has to be discussed. A higher dose leads to a blockage of the receptor binding of In-111 octreotide. The clinical role of SPET in the evaluation of brain perfusion (BP) is well established, while the significance of abnormal visualization of intracranial vessels with MRA has to be assessed. The aim of the study was to correlate the appearance of intracranial arteries at MRA with SPET images in 24 patients with BP abnormalities indicative of cerebrovascular disease (CVD). SPET studies were performed after i.v. injection of 740 MBq 99mTc-HMPAO using a high-resolution system (CERASPECT, DSI). The presence of either focal or diffuse cortical perfusion defects or of marked left-right asymmetry were considered abnormal findings at SPET. A conventional MR brain scan (1.5 Tesla, Magnetom, Siemens) was followed by the acquisition of 3D-tirne-of-flight MRA sequences for the study of intracranial arteries (TR=36-43 msec, TE=6-8 msec, Flip angle=15°). MRA studies were considered abnormal if major intraeranial arteries showed narrowing or reducedabsent signal, or if their peripheral branches had decreased visualization. SPET and MRA abnormalities were concordant in 12 cases. MRA was rated normal in 5 patients with focal BP defects and/or marked asymmetry, and in 5 patients with globally decreased cortical perfusion. In the remaining 2 patients with frontal and fronto-parietal BP defects, reduced visualization of peripheral cerebral vessels were observed in the contralateral hemisphere. MRA documented the "anatomic" correlation to the BP abnormalities in 50% of the cases; on the other hand, several factors may modify blood delivery to the parenchyma independently from the status of feeding arteries, and this could justify the findings in the other patients. MRA seems able to provide useful complementary anatomic information in the diagnostic work-up of patients with CVD, with little extra scan time after a conventional MR brain scan. In order to obtain a data base for activation studies, the normal values and the reproducibility of Tc-g9m HMPAO regional cerebral uptake measurements were assessed in 16 young healthy volunteers. I f studies were repeated in identical conditions within 72 hours. All studies were processed by two observers unaware of each others results. Five minutes after the injection of 20 mCi Tc-99m HMPAO, a SPECT acquisition, 64 steps of 30 sec over 360% was started on a 3head Multispect Siemens gamma camera (192 images). After backprojection using a Butterworth filter (cutoff 0.5), Chang's attenuation correction and, reorientation according to the orbito-meatal line, 5 transverse 14 mm thick slices were defined: the lowest slice containing the cerebellum and temporal lobes, the second through the basal ganglia and thalamus and, 3 consecutive cortical slices. A threshold of 50% was used in the lowest 2 slices for manual delineation of the regions, according to a cerebral atlas, (5 and 6 mirrored regions respectively); a threshold of 65% was used for the automatic sectorisation in the upper 3 slices (6 mirrored regions in each slice). Thus 58 (2x29) vascular ROIs were defined over transverse slices in each volunteer. All regions were normalized to the maximal cerebellar activity. For each of the 58 segments, the 95% confidence interval on the mean uptake values ranged between 2.7% and 9.37%. The variation coefficient for the left to right ratios varied between 2.1% for the thalamus and 5.3% for the latero-frontal upper segment. The interobserver variation coefficient for the different regional uptake values ranged from 1.92% to 7.29%. The interstudy variation coefficient for the different regional uptake values varied between 2.50% and 5.91%. Thus, in normal volunteers, using a 3-head multispect gamma camera, very strict reference values were obtained which can be used for interindividual, intergroup and interstudy comparisons. (ATR), is accompanied by vascular dementia which was reported to be caused b y U and DWML. 51 pts. with CMA were scrutinized for changes in rCBF and rMRGlu in both WM and cortex. The results were correlated with MRI-findings. A special head holder system provided exact repositioning during examination of rCBF (15 min p.i.,740 MBq 99mTc-HMPAO -SPECT) and rMRGlu (30 min. p.i.,300 MBq 18 FDG-PET) and MRI. WM and cortex were quantitated with ROIs defined in MRI and superimposed to corresponding PET/ SPECT slices (overlay). Glucose utilization (rMRGlu) was derived from the autoradiographic method, regional cerebral perfusion (rCBF) from normalization to cerebellum. I_1 and DWML were divided in two groups (= microangiopathy-score): 1) < 4 LI, no DWML, 2) • 4 LI, m=ddle to severe DWML. For ATR a twolge grading was used: A) no to only slight inner and/or outer ATR middle to severe outer and inner ATR. 10.5+4.7:1: t 32.8-+10.1" I :t: P < 0.0. ' p ~ 0.025 significance of A) is.B) Pts. of B) ~c,w d significant lower rCBF-=,nd rMRGlu-values both in cortex ant A M ;han A). Thus since reduced rCBF-and rMRGlu-vaues n CMA are not corre ated to LI and DWML but to outer and inner ATR, the concept of vascuar dementia may be incorrect. Subsequent inner and outer atrophy may be responsible for functional (and clinical) presentation of such pts. In this prospective study, cerebral peffusion reserve (CPR) was evaluated by acetazolamide (Diamox) 99m-Tc-HMPAO brain SPECT in patients clinically suspected for carotid artery stenosis. Consecutive 99m-Tc-HMPAO brain SPECT investigations were obtained within one hour before and after a dose of 1000 mg acetazolamide iv. Studies were performed with a SME 810 multidetector neuroSPECT system. After reconstruction mean counts in the parieto-occipltal region were calculated on fixed regions of interest (ROl's) in two slices. The calculated activity was corrected for injected dose 99m-Tc-HMPAO and decay. The corrected counts of the baseline study were subtrated from the post-Diamox study. The increase in pedusion, the CPR, was expressed as a percentage of the baseline resu~ in the same RO1. Sixteen studies were performed in 15 patients, 5 woman and I I men, mean age 66 years, range 42-81 years. The results of 16 studies (32 carotid arteries) were used for statistical analysis. A carotid stenosis was considered significant above 70% (duplex sonography or angiography 27.3% ± 13, 1% 12-53% The patient who was investigated a second time after succesful endarterectomy of a 95% carotid stenosis showed a significant increase of cerebral perfusion reserve from 12% to 33%. Conclusions: In these small series of patients the cerebral perfusion reserve, compared with normal arteries, was significantly lower (p=0,004) in patients with carotid artery stenosis above 70%. No difference was seen between normal and total occluded arteries, suggesting adequate collateral blood supply. Lack of difference between normals and non significant stenoses can indicate the clinical non significance of these stenoses, Further studies should be performed to relate the CPR will risk reduction for CVA's in the follow up of these patients. The aim of the present prospective study was to evaluate the haemodynamic significance of asymptomatic cerebral embolism in patients undergoing carotid endartectomy (CEA). In a series of 22 patients (two patients had both sides operated sequentially), MRI revealed small single or multiple emboli after five CEAs. Cerebral perfusion reserve (CPR) was measured just before and one month after CEA by performing Tc-99m-HMPAO SPET both before and after intravenous injection acetazolamide (dose I g). CPR was calculated for the whole 10.5 mm thick transverse slice as well as for the symmetrical ipsi-and contralateral ROIs representing the affected embolic and contralateral areas. Before CEA, regional ipsi-and contralateral CPRs were symmetrical (5 vs ii %, ns). After CEA, ipsilateral CPR decreased to -3 %. The contralateral CPR remained unchanged (8 %), and it was significantly higher than on the ipsilateral side after CEA (p<0.05). The CPR for the whole slice showed a slight decrease (13 % vs 3 %, ns). These preliminary findings suggest that asymptomatic cerebral embolism during CEA decreases ipsilateral regional vascular reactivity. Normal pressure hydrocephalus (NPH) can be cured by surgical derivation but morbidity of such treatment is high indeed. Iterative lumbar puncture can induce clinical and cerebral blood flow improvement, Chronic treatment with acetazolamide (0,5 g per day) can also improve clinical status after a few weeks (1, 2). We undertook to measure brain perfusion by 99mTc HMPAO SPECT (740 MBq) before and after 4 to 6 week-treatment with acetazolamide in 5 patients (age 42 to 86 years). All patients demonstrated ventricular enlargment on CT, and were suffering from gait and walking disturbances and anterograde amnesia. Their clinical status was assessed by a Mini Mental Test (3MT) and a Hachinski Test. SPECT demonstrated a decreased regional blood flow in hippocampal areas, in frontal and white matter parietal cortex. Acetazolamide treatment was effective in 4/5 patients, with 3MT improvement, even normalization in 2/5. The nonresponding patient (42 years) had a non communicating congenital hydrocephalus. Accordingly, brain perfusion assessed quantitatively with a standard dose was dramatically improved (range 20 to 75%) in all patients with clinical improvement (4/5). The patient not clinically improved did not demonstrate any brain perfusion increase after acetazolamide. We concluded that 99mTc HMPAO brain SPECT may be a non invasive and objective imaging procedure to assess acetazolamide efficiency in patients suffering from NPH, matching well with clinical status, A on going expertise is done on a cohort of 9 patients with the same protocol to assess regional increase of flow in psychiatric improved patients after DIAMOX. -(1) Aimard G, Vighetto A, Gabet JY et al : Acetazolamide : une alternative ~ la d6rivation darts l'hydroc6phalie ~ pression normale. R6sultats pr61iminaires. Rev. Neurol. Paris 1990, 146:6-7 ; 437-439. -(2) Larson A, Bergh AC, Bilting M, Arlig A, Jacobson L, Stephenson H, Wikkels6 C : regional cerebral blood flow in NPH : diagnostic and pronostic aspects. Eur J Nucl Med 1994, 21:118-123. In the surgery of turnouts, metastases and aneurysms affecting the carotid vessels, in some cases resection of the internal carotid artery (ICA) is needed. To predict the tolerance of permanent ICA resection, a balloon test occlusion is recommended. The procedure is commonly combined with 99mTc-HMPAO SPECT and recently also sensitized with acetazolamide. The aim of our study was to determine the quantitative criteria of pathological rCBF patterns in this test. In 17 patients with oropharyngeal tumours, a balloon test occlusion with acetazolamide (1 g) (stress study) combined with a high resolution SPECT (CERASPECT) and 99mTc-HMPAO were performed besides continuous clinical and transcranial Doppler sonographical (TCD) monitoring.. In 8 cases the rCBF SPECT was repeated under resting condition. The patients in groups with normal and pathological reaction were categorized according to the clinical signs and symptoms, the TCD findings and the postoperative outcome. The rCBF SPECT data with an automatic ROI method were analysed. The asymmetry of 99mTc-HMPAO uptake in percent and its changes compared to the rest study were determined at the global cortex, the medial cerebral artery (MCA) territory, and the watershed zones. The rCBF SPECT asymmetry values of the cortex, and of the watershed zone showed a statistically significant correlation with the TCD results (0.67, p<0.01 and 0.62, p<0.01 respectively, Spearman rank correlation), but not with the MCA territory. In the group of patients with normal reaction (n=11) during the test occlusion the side difference on SPECT was 5+2% in the cortex, 8+5% at the MCA region, and 9_+6% in the watershed zone. The corresponding data for the changes between rest and stress condition (n=5) were 2_+2, 2_+2, and 2_+3, respectively. In the differentiation between normal and pathological reactions, a threshold value of 15% in the watershed zone at the stress study gave a sensitivity of 5/6, and a specificity of 11/11. We concluded': 1. Quantitative analyses of rCBF SPECT data give objective criteria in the interpretation of ICA occlusion tests with acetazolamide. 2. The rCBF alterations in the watershed zones seem to be especially valuable. 3. In the suspicion of anamnestic rCBF disturbances rCBF SPECT under rest condition is also needed. The safety of and tolerance for radiolabeled monoclonal antibodies was evaluated in a study in which B cell lymphoma was treated with increased doses of anti-CD20 labeled with yttrium-90. Therapy was preceded by bone marrow or peripheral stem cell harvesting with purging. Doses were planned to increase in four steps (10, 20, 30, 40) to 40 millicurie, and bone marrow toxicity to be handled with autologous bone marrow transplantation. The infusion of the radiolabeled agent was preceded by an infusion of img/kg of unlabeled antibody. No bone marrow transplantation was necessary for the 9 patients who received up to 30 millicurie (three last ones), but 4 patients received G-CSF support. Leukopenia ( 8 yaers) belonged to the HTD group. Tumor marker responses (VMA, HVA) did not differ between the groups. The immediate toxic bone marrow response based on leucocyte and thrombocyte counts was comparable for both groups. Despite a low tumor uptake a long remission of more than 24 months was achieved in 1 child. 131I-metaiodobenzylguanidine (MIBG) is associated with a reduction in the circulating platelets,thrombocytopenia being the major factor limiting the therapeutic application of a 13tI-MIBG therapy.In order to assess the potencial radiation hazard, we therefore investigated the platelet uptake mechanism of 131I-MJBG in-vitro and in-vivo. The influence of plateletdensity, temperature and time of incubation and amount of radioactivity were analysed as well as the effect of iv administration of 131I-M~G for diagnosing on platelet count, viability and blood cell uptake invivo.Venous blood from healthy volunteers (n=182) and patients with (n =17) and without(n=9) g-blockers was studied.In-vitro studies included varying conditions: plateIet-density (1.107, 1.10 s, 1.109 platelets/ml), temperature of incubation (4°C, 22°C, 37°C), time of incubation (5, 10, 30, 60 rain) and amount of radioactivity (0.01, 0.1, 1 uCi). When bacreasing the number of platelets a progressively higher cellular uptake was found. This uptake was temperature -and time -dependent, while it was not influenced by inereasig amounts of radioactivity. No difference in platelet uptake between volunteers and patients without 13blockers was found, while platelets derived from patients under 13blockers did not show that selective uptake. After a diagnostic application of 500 uCi 131I-MIBG In-vivo a selective uptake by platelets occurred too, resulting in a platelet to plasma ratio of up to 1:32. Even at~er a diagnostic dose a nadir of platelet count down up to 36% (maximum at 7 days) was observed. Patients under B-blockers did not show a change in their platelet count, the platelet plasma ratio did not exceed l:4.4.These in-vitro and in-vivo findings suggest that 131I-MIBG is actively taken up by blood platelets by a mechanism being dependent on the concentration of platelets, the temperature and the time, which is inibited by B-blockers. This selective uptake may explain the major irradiation hazard of 13II-MIBG. M.Stoffel, F. Jamar, N.Leners, C.Beckers, A.Ferrant and S.Pauwels. Depts. of Nuclear Medicine and Hematology, University of Louvain Medical School, Brussels, Belgium. Discordant mIn-P results have been reported in lymphoma patients (pts) according to the cell-type and grade of malignity. Our study was performed in order to evaluate the sensitivity of NIIn-P in 17 pts with histology-proven lymphoma, including 4 pts with Hodgkin's (HL, 4 studies) and 13 non-Hodgkin's lymphomas: 5 low-grade (1NHL, 7 studies), 2 intermediate-grade (iNHL, 3 studies) and 6 high-grade (hNHL, 8 studies). Planar (4h, 24h) and SPECT (24h) acquisitions were performed after injection of-200MBq tHIn-P. The scintigraphic findings were compared with conventional imaging modalities (CIM) and histology when available. mIn-P was +ve in 7 new cases, 3 recurrences and 5 residual diseases. One of 2 refractory pts was mIn-P +ve (iNHL) whereas the other was -ve (1NHL). mIn-P was -ve in 4 of the 5 complete remissions whereas in 1 pt a stable lymph node remained +ve aider radiotherapy. mIn-P detected 21 of the 28 lesions recognized by CIM: the sensitivity per lesion was 100%, 78%, 80% and 64%, in HL, hNHL, iNHL and 1NHL respectively. The -ve sites included 2 lymph nodes, 1 spleen infiltration, 1 liver, 1 bone and 1 meninges lesion, mIn-P detected 9 unsuspected lesions: 1 true +ve, 5 unconfirmed and 3 false +ve (2 infectious sites, 1 external contamination). Nine of the 11 biopsied lesions (9 pts) were ~In-P +ve (82%). In all but 2 pts (2 INHL), mIn-P and CIM resulted in an identical pt staging. Conclusions: t) our results indicate the potential usefulness of ~In-P for staging of lymphomas, particularly in HL patients, 2) data interpretation should be cautious in patients with potential infectious complications. In the pilot study, approx. 925 MBq (25 mCi) of the Tc-99m labeled Mab (1 rag) was injected iv in 16 patients. At 30min, 3-4 h, and 24 h p.i, whole body images were obtained. Planar imaging was performed at lh, 3-4 and 24h p.i:, SPECT 4-5h p.i. HAMA were determined using the ImmuStrip® HAMA ELISA (Immunomedics). The agent was tolerated well with no adverse reactions. The half life for the total body ranged between 44 and 58h. Dosimetry data revealed the highest dose for spleen and kidney (0.15-0.24 and 0.28-0.33cGy/mCi, respectively; total body 0.01-0.02 cGy/mCi). In the Phase 1 study (10 pts), 3 different doses (0.5, 1, and 5mg) of LL2 were administered, all revealing similar elimination half-times. 24 pts were enrolled in the Phase II trial (30 mCi Tc-99m, 0.25-1mg Fab'). All pts underwent non-invasive imaging (CT, chest x-ray, MRI, bone scan, Ga-67 scan) and the results were compared to RAID scans. The efficacy analysis in the 43 evaluable pts demonstrated a sensitivity of 86%, an accuracy of 86%, and a positive predictive value of 100%. Only 1 pt at the 5 mg dose and another pt at the 1 mg dose developed a positive HAMA response. The Tc-99m-IMMU-LL2 antibody fragment appears to be a safe and accurate imaging agent. With regards to staging, in 11/43 cases, RAID correctly identified all areas of disease previously diagnosed by 2-3 separate, different diagnostic modalities and in another 11/43 cases, identified additional tumor sites not detected by any other previous diagnostic procedure; 10/58 pts were upstaged. Based on managing physician judgements, 29/43 (67%) of pts had clinical benefit as defined by confirmation of disease extent (25 pts), upstaging (6 pts is not sensitive enough, and whole-body imaging is not possible by CT or MRI. BM scintigraphy (BMS) has been proposed to detect focal EM replacement by space-occupying lesions. In our study 56 patients with various types of malignant lymphomas were evaluated by ES and EMS. Tc-99m-MDP and Tc-99m-labeled antigranulocyte antibody were used. In selected cases BM biopsy, X-ray, CT or MRI examinations of suspected regions were also performed. Diagnostic values of BS and BMS in different patients groups and regions (skull, vertebra, ribs, pelvic region and extremities) were evaluated on a lesion-by lesion basis.Results: BMS proved to be insensitive for detection of BM involvement of the skull and the ribs, but is an accurate method for detecting vertebral lesions in all groups of patients (sensitivity:.88 specificity:.96). In the pelvic region EMS is not sensitive(.34). No lesion of the extremities was found in patients without localized pain. Diagnostic accuracy of BMS is higher than that of BS in patients with malignant lymphoma (.76 vs .52). BMS proved to be reliable for evaluation of BM reserve function in patients with multiple myeloma. In conclusion:problem-oriented use of BMS using antigranulooyte antibody is indicated in patients with malignant lymphomas. Weightlessness induces changes on blood cells, body fluids and electrolytes which can be simulated by head-down-tilt studies (HDT). Sodium (Na) intake might be responsible for some changes. We investigated 12 healthy volunteers with 4 MBq 51Cr in-vitro labeled red blood cells (RBC). Governmental permission was obtained. Group I (GI, n=6) was evaluated with 10 days 6 ° HDT with strict diet control. Group II (GII, n=6) was investigated with increasing Na intake (three 8 days periods: 2.8 -> 5.6 -> 8.4 mmol Na/kg BW). Half-life of RBC (T1/2RBC) was calculated by using 5~Cr counts (CrC) of blood samples (BS). To calculate blood volume (BV) the CrCs were corrected by the T1/2RBC, the total volume of BS, T1/2 of 51Cr and an activity loss of the RBCs of 2%/day. Plasma (PV)-and RBC-volume (RBCV) was then calculated by using the hematocrit. In GI Na loss of 80 mmol was observed during the first days of HDT and Na retention during recovery. PV was reduced by 16% and returned to normal during recovery whereas RBCV remained constant. TI/2RBC was slightly reduced (p <0.4). In GII Na-and urodilatin (natriuretic peptide)-excretion increased with increasing levels of Na intake (p < 0.006) whereas urine flow remained unaffected. BV increased linearily with Na intake resulting in a raise of maximally 0.6 1 __ 0.13 1 (p < 0,05). This was accompanied by a decrease in vasopressin, and renin-aldosteron levels. The metabolic Na balance revealed a Na storage without changes in serum Na concentration and -osmolality. T1/2RBC decreased significantly by 7.5 days (p < 0.05). We conclude, that microgravity and Na intake significantly affects the composition of body fluids and cells which can be accurately measured by the S~Cr-method and urodilatin appears to contribute to the day-to-day Na balance. T. Lutz, C. Vo, and D.M. Lyster. TRIUMF, Department of Pharm. Sci.,University of British Columbia, Vancouver General Hospital, British Columbia, Canada. Although F-18-2-fluoro-2-deoxyglucose (FDG) is the optimum agent used in heart and brain imaging, it is not routinely available. Due to the advantages of using a gamma emitting nuclide, several researchers have studied 1-123 iodo glucose analogues, but none have shown any localization in heart or brain tissues. Unfortunately 2-IDG is not stable enough to be isolated. Therefore we proposed the synthesis of 2-iodo-2-deoxy-l,5-anhydro-D-glucitol (2-IDAG) where the Cl hydroxyl has been replaced by a hydrogen so as to stabilize the compound. This was a synthetic challenge starting with 1,5-anhydro-D-mannitol (1,5-AM) due to the similar reactivity properties of the C2 and C4 hydroxyls. 3,6-dipivaloyl-l,5-anhydro-Dmannitol (3,6-PM) was prepared by the addition of a 2:1 ratio of pivaleyl chloride:l,5-AM in 50% yield. 3,6-PM was then iodinated to give 3,6-dipivaloyl-2-iodo-l,5-anhydro-D-glucitol (3,6-PIG) which was purified by HPLC. Compounds were characterized by elemental analyses, and NMR. 3,6-PM was also selectively mesylated at the C2 position to give 2-Ms-3,6-PM, which was used as a precursor for radioiodination. Under various reaction conditions, no radiolabelling was observed using 1-123. We therefore exchange labelled 3,6-PIG obtaining 97.5% radiochemical purity. Biodistribution studies in mice showed 1.67% heart and 0.83% brain uptake at 30 minutes post injection. SCINTIGRAPHY AND KINETIC STUDY OF AMYLOID DEPOSITS WITH 131-I SAP In this study we report on 7 pts with AL amyloidosis (13 studies) investigated employing SAP, a normal plasma glycoprotein that deposits on amyloid f i b r i l s , labelled with 131-I. Previous injection of 25-40 HBq of 131-I SAP, a whole body scan was carried out and repeated after 1,2,3,5 and 7 days; venous blood samples and urine were collected throughout the study. Whole body and organ retention of radioactivity were calculated from geometrical mean values and compared with the baseline scan. Six studies were performed in 4 pts after experimental therapy with an anthracycline derivate. Acceleration of i n i t i a l plasma clearance and increase in whole body retention were noted in pts with extensive amyloid deposits. In 4 pts imaging showed involvement of the spleen, in 3 of the liver, in 2 of kidneys and bone marrow; 3 pts had an equivocal uptake respectively in heart, kidneys and adrenals. One pt with low whole body retention and normal plasma clearance, in whom biopsy did not confirm the presence of amyloidosis, showed no significant focal uptake. All cases but o n e , presenting a large amyloid deposit involving the sacrum, showed no appreciable differences after treatment, although in 2 pts there were minor changes in plasma clearance and whole body retention indicating an increased sequestration of SAP into amyloid deposits. Despite the unfavourable physical carachteristics of 131-I and the low dose administered, these studies provide detailed information on the quantity and distribution of visceral AL amyloid deposits. Institut fur Nuklearchemie, Forschungszentrum J'alich GmbH, 52425 J/Jlich, Germany A NEW RADIOIODINATED AMINO ACID FOR MEASURING AMINO ACID TRANSPORT WITH SPET 3-Iodo-L-~-methyltyrosine (IMT), has been shown to be a useful tracer for amino acid transport and has found application in tumour studies with Single Photon Emission Tomography (SPET) (Biersack et al., J. Nucl. Med. 1989, 30: 110-112; Langen et al., J. Nucl. Med. 1990 , 31: 281-286, and ibid. 1991 , 32: 1225 -1228 . However, the brain uptake of IMT is poor, and only allows the visualization of increased rather than decreased incorporation. We have therefore prepared and evaluated O-methylated radioiodinated tyrosines in order to increase their lipophilicities. Direct eleetrophilic n.e.a, radioiodination of the anisol-like aromatic moieties using the well known Chloramine-T (CAT) method resulted in unsatisfactory yields. Using tfifluoroacetic acid (TFA) containing 10 vol.% water as a reaction solvent radiochemical yields of 40% of 3-[123I]Iodo-O-methyl-L-tyrosine (IOMT) and 3-[I23I]Iodo-O-metbyl-L-~-methyltyrosine (IOMMT) could be obtained at 60°C in 5 rain reaction time. Use of Iodo-gen TM as an oxidant instead of CAT gave rise to RCY of 60% at 60°C in 45 rain reaction time. In contrast to the normally used two phase system Iodo-gen~/water our labelling reactions were performed in a homogeneous medium. IMT can be obtained in RCY's of 80% in 10 rain at RT using Iodogen TM in the normal aqeous two phase system at pH=8. Biodistribution studies with NMRI mice revealed a maximal brain uptake of the compounds that parallels their lipophilicities: IMT 99% and a specific activity of > 4 GBq/gmol within 2 h. Animal studies were performed in non-fasted Sprague-Dawley rats. While myocardial biokinetic was comparable to the results obtained in fasted animals, liver activity drops from 5% I.D./g (5 rain pi.) to 1.5% I.D./g (30 rain pi.) and 0.6% I.D./g (4 h pi.), in contrast to 3% ID./g (4 h p.i.) retained in the liver of fasted rats. Treatment of non-fasted animals with Etomoxir (20 mg/kg) prior to injection of [I-123]-PHIPA 3-10 resulted in significant biokinetic differences. Myocardial activity accumulates significantly with time from 3.8% I.DJg iodoacylated p-Iodoaniline and iodoacylated l-Iodoallylamine were prepared. For the aniline derivative yields of about 70% were obtained by a two step one-pot synthesis (iodination of aniline and subsequent iodoacylation of p-iodoaniline). In case of the vinyl derivative the radio-synthesis requires a stannylated precursor giving rise to almost quantitative iodination yields in one step. Both reagents reacted quickly and quantitative with cysteine at pH 7.5. Labeling of proteins was demonstrated using BSA as a model compound. In this case, coupling rates were higher using the aniline derivative and reached 40% RCY at pH 9, where amine labeling would predominate. Lower yields of 25% (aniline) and 15% (vinyl t h o x y b e n z a m i d e as a potential 5HT_, receptor t r a c e r for SPET. Within a series of halogenated derivatives of 4-amino-N-[1- [3-(4fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-halo-2-methoxybenzamide, a new class of potential 5HT2 antagonists, it was shown that the 5-iodo-2-methoxybenzamide analogue showed a high affinity (Ki for inhibition of [3H]ketanserin binding to rat frontal cortex membranes 0.22 nM) and high selectivity for 5HT~receptors (selectivity with regard to other neurotransmitter receptorsites of at least a factor 50). Therefore the pure N.C.A. radioiodinated analogue was synthetised and evaluated in vitro and in vivo in rats. Scatchard analysis of saturation binding to rat frontal cortex membranes of the 1-125 labelled compound revealed a linear plot yielding a Kd of 0.11 + 0.01 nM and a Bmax value of 37.79 +_ 0.75 fmol/mg tissue. The binding occured reversibly on one single type of receptor, i.e. 5HT2. From 1 hour up to 3 hours after i.v. injection into the tail vain of rats the frontal cortex to cerebellum ratio showed a steady state value of about 8-9 and the frontal cortex to blood ratio a value of 5 6. The striatum/cerebellum and striatum/blood amounted to about half that value. Inhibition and displacement by Ritanserin and Ketanserin showed that binding to 5HT 2 receptors was involved. Two hours after injection the %ID/g in frontal cortex was 0.24 and in striatum was 0.12 while in the total brain (frontal cortex and striatum included) this value amounts to 0.087 which means a ratio of at least 3 for frontal cortex and 2 for the striatum versus the rest of the brain. These results show that, if the behavior in human will be comparable, this new compound is really promising for visualisation of 5HT2 receptors with SPET. Montserrat Estorch, Ignasi Card6, Jos6 I_opez-Pousa, Lluis Bern~i, Gustavo Tortes. Hospital de Sant Pau, Barcelona. UPTAKE RELATES TO AGE Fourty cancer patients, enrolled in a study to assess the effect of doxorubicin administration on adrenergic neuron function, underwent baseline studies with I~3I-MIBG before chemotherapy. None of the patients had a history of previous cardiac disease or previous chemotherapy or mediastinal radiotherapy. MIBG uptake was quantified by a mediastinum to heart ratio (MHR) 4 hrs after i.v. administration of 5 mCi of ~I-MIBG. Mem~ age of patients was 36 years, ranging from 16 to 75. Six patients were below 20 years, 9 patients were between 20 and 40 years, 12 patients were between 40 and 60 years and 13 patients were over 60 years of age. Myocardial ~I-MIBG uptake was observed in all patients with a mean MHR of 1.85+0.29, range 1.31 to 2.62. MHR correlated to age (r=-0.6264, p<0.001). A decline in ~=~I-MIBG with increasing age was observed. Mean MHR of patients of < 20 years was 2.06, of patients between 20-40 years was 1.90, of patients between 40-60 years was 1.86, and of patients > 60 years was 1.55. The best separation was observed comparing patients who were >60 years (mean MHR of 1.55_+0.t5, range 1.31-1.78) with patients who were <60 years (mean MHR of 1.95+0.26, range 1.45-2.62, p=0.003); mean EF in both groups was similar: 56+7% and 60_+7%, p=NS. We conclude that intensity of myocardial ~I-MIBG uptake relates to age. A decrease in MIBG uptake is observed with aging, specially in those patients over 60 years. This has to be taken into account when designing studies to assess cardiac adrenergic neuron function with ~I-MIBG. Myocardial adrenergic innervation is disturbed in patients (pts) with congestive heart failure (CHF). 1-123-m.~taiodobenzylguanidine (MIBG) is useful in assessing adrenergic cardiac innervation in those pts.To examine possible prognostic value of 1-123 MIBG scintigraphy in CHF we analyzed data from 31CHF pts. Age was 52±13 years, 30 pts were men, 13 pts were in Class I / I I and 18 pts in Class I l l / I V . 15 pts had dilated cardiomyopathy, 12 ischemic cardiomyopathy and 4 pts valvular heart disease. Ejection fraction was 16±9%, mean right atrial pressure (RA) 10±5 mmHg, mean pulmonary artery pressure (PA) 41±11 mmHg and mean pulmonary capillary wedge pressure (PCWP) 26±7 mmHg. Scintigraphy was performed 4 hours after intravenous injection of 5 mCi 1-123 MIBG; uptake was assessed as heart to mediastinum ratio (H/M). Mean H/M in CHF pts was 1,40±0,24; there were not differences between ischemic, dilated and valvular disease and between Class 1/11 and I l l / I V pts. H/M showed a significant correlation with EF (r=0,53, pI,2 4 pts died during follow-up; within 6 months 1 pt died and i pt deteriorated (0,01 HMPAO in 51/52 patients (exception 1 abcess). Conclusions: 1. The IMT uptake in cerebral gliomas is dominated by amino acid transport and not by perfusion (HMAPO). 2. IMT-SPECT provides important prognostic and additional information in all types of primary brain tumors, esp. after IORT. 3. IMT-SPECT is comparable to PET in patients with brain tumors. The uptake indicates early a poor prognosis regardless of histologic diagnosis or previous therapy. ]iodo-0t-methyltyrosine (IMT) has been shown to be a tracer of amino acid transport. This study investigates the determination of rate constants of amino acid transport in brain tumors and normal brain using dynamic IMT SPECT. Ten patients with cerebral gliomas were investigated by dynamic SPECT using a triple-headed system after i.v. injection of no carrier added (n.c.a.) IMT (8 scans ~ 2 min., 9 scans ~i 5 min.). For comparison, dynamic PET studies after injection of n.e.a. [methyl-C-11]-L-methionine (MET) were performed on the same day. The plasma input functions were determined and corrected for metabolites. The SPECT scanner was calibrated against the well counter by brain phantom studies and the SPECT scans corrected for attenuation by individual contour finding. The kinetics of IMT in plasma, brain and brain tumors were evaluated by Logan plots for 2-compartment models and the kinetics of MET by Patlak plots to determine the rate constant of unidirectional influx, Ki. The Logan plots of IMT kinetics were linear for tumors and normal brain in all subjects and allowed the calculation of the influx and backflow rate constant K1 and k2 oflMT transport. K1 values were significantly higher for tumors than for normal brain (0.120 :L 0.044 vs. 0.055 * 0.020, n=10, p<0.01)) as were the Ki values for MET (0.044 -4-0.018 vs 0.020 :t: 0.007, n=10, p<0.01). However, no significant correlation of the K1 values of IMT and the Ki values of MET could be found in this group of patients. In conclusion, dynamic IMT SPECT appears to be capable to determine the rate constants of amino acid transport in brain and brain tumors. The lack of correlation with MET influx may indicate that SPECT quantification has still to be improved and needs sophisticated scatter correction and attenuation correction by measured transmission scans. Infection and inflammation are characterized by an influx of activated leukoeytes, being predominantly interleukin-l-receptor positive cells, Interleukin-1 (IL-1) has a high affinity for its receptor and might therefore be able to specifically localize in the infectious or inflammatory tissue. We investigated whether recombinant human IL-I can be used for imaging infectious foci in vivo in mice and rats. IL-lc~ was radiolabeled with 1-125 via the glucose-oxidase/lactoperoxidase method, resulting in a specific activity of 60 -120 ~tCi//tg. The receptor binding fraction in vitro, determined on EL-4 thymoma cells, was 70-95%. 24 Hr after induction of a S. Aurens abscess in the left calf muscle, 25 Swiss mice (20-25 g) were i.v. injected with 0.2 ml 10/~Ci 1-125-IL-1~. Groups of five mice were sacrificed at 2, 6, 12, 24 and 48 hr p.L Activity uptake was assessed in the blood, muscle, abscess, thymus, thyroid, lung, spleen, kidney, liver and intestine. Gamma camera images were obtained by injecting rats i.v. with 400 #Ci 1-131-1L-I~. 1-125-1L-lot was rapidly cleared from the blood; 12 hr p.i. the activity had decreased to less than 05% ID/g. After 12 hr, the abscess was the organ with the highest activity (1.02 _+ 0.23 %lD/g). The abscess/muscle ratios sharply rose from 3.2 + 0.5 at 2 hr p.i. to an ultimate value of 37.0 _+ 13.2 at 48 hr p.i., whereas the ratios of a control agent, 5-Lactoglobulin, only slightly increased from 3.1 + 0.6 to 5.0 + 0.8 at 2 and 48 hr p.i. respectively. The ratios of 1-125-IL-le~ were significantly higher from 12 hr onwards (Wileoxon-Rank test, p<0.008), The abscesses were dearly visualized at 12, 24 and 48 hr pi. Our results demonstrate specific retention of IL-1 in the abscess, presumably by interaction of IL-1 with its receptor on the inflammatory cells. The high target-to-background ratios that were obtained relatively shortly after injection indicate that IL-1 may be a valuable agent to image infectious foci. In-111 and Tc-99m labeled human polyclonal immunoglobulin G (hlgG) are of clinical use for detection of sites of infection. Previously we reported on the role of release of In-111 from In-111-hlgG in the retention of the indium label in foci of infection. This study focuses on the release of Tc-99m from Tc-99m-hlgG in infectious fool, comparing two different Tc-99m-hlgG preparations with In-111-hlgG. Tc-99m-labeled nicotinyl hydrazino hlgG (Johnson Matthey, JM) and Tc-99m-labeled 2-iminothiolane-modified hlgG (Mallinckrodt Diagnostica, MD) were both labeled with C-14 by methytation, using C-14formaldehyde, and pudfied by gel filtration. DTPA-conjugated hlgG was labeled with In-111 by citrate transchelation and used as such. HPLC was performed as quality control. Young Wistar rats with a S. Aureus infection of the left calf muscle were i.v. injected with either 6 MBq Tc-99m and 40 KBq C-14 labeled to 130 or 50 pg hlgG (JM resp. MD) or 2 MBq In-1tl labeled to 80 ~ hlgG. Rats were sacrificed at 2, 6, or 24 hr p.i. Averages ± SD in=5) of percentages of dose per gram (%lD/g) were determined for plasma, udne, abscess, and vadous other tissues. Plasma and udne samples were analyzed by HPLC. The radiochemical pudty was > 96%. Tc-99m-hlgG (JM) was better retained in abscesses and had a slower plasma clearance than both Tc-99m-hlgG (MD) and ln-111-hlgG (24 hr p.L %lD/g abscess: JM: 1.48; ME): .84; In: 1.10; p<0.01; plasma: 3.24 resp. 1.69 and 1.28; p<0.01; abscess/muscle: 9.0 resp. 6.5 and 6.3). In abscesses the Tc-99m1C-14 ratio increased over time. The renal uptake of Tc-99m-hlgG (JM) at 24 hr p.i. was lower than for both other agents (%ID/g kidney: JM: 1.45; MD: 5.07; In: 4.57; p<0.01). In plasma a small quantity of only one Tc-99m-labeled metabolite was found with a higher molecular weight than hlgG. In conclusion: Tc-99m-labeled nicotinyl hydrazino hlgG (JM) seems an attractive agent for localization of infections. As In-1tl, Tc-99m is retained in infectious foci, whereas IgG or its metabolites are released. Tuftsin, a tetrapeptide derived from the Fc portion of !gG, promotes phagocytosis and chemotaxis of neutrophils and monocyte/ macrophages by a receptor-mediated mechanism. Given the uniqueness of the receptor for these cells, we have attempted to use tuftsin antagonist(TKPPR) as a targeting moiety for inflammation imaging. The peptide was synthesized with an N3S peptidic chelation site (Pic-SC(Aem)G; Pic = picolinic acid) attached at the N terminus. It was easily labelled with Tc~99m by transchelation from glucoheptonate. Typical radiochemical purities were in the range of 91 -97%. Labelled peptide was administered intravenously (i00 ~Ci/0.6 ~g dose) to rats with infectious (E. coli) inflammation of the right thigh and excellent scintigraphic images of the site were obtained within 0.Sh of injection. Measurements of radioactivity in tissues excised 0.5, 3 and 17h post-injection revealed target to background ratios of 3.6, 5.0 and 16.2 respectively (n = 2 -4). Elimination was primarily renal with 80.6% of the dose in the bladder at 3h. In conclusion, the tuftsin antagonist TKPPR has excellent potential as a targeting agent for inflammation imaging. The kinetic data and whole body distribution of a new Tc-99mantigranulocyte Fab'-fragment iNCA-90; IMMU-MN3) were prospectively examined in 10 patients with suspected osteomyelitis and/or fever, who were injected with 185-900 MBq(0.1-1.0mg) of the labelled fragment. Blood specimens (5 ml ) were drawn 5, 15, 30, 45 and 60 min, 4h and 24h postinjection for calculation of the recovery rate of the antibody in whole blood. After isolation of pure granutocytes on a PERCOLL/plasma gradient, the antibody distribution in the gradient was imaged with a gamma camera and calculated by ROI-technique. Whole body scans I h ,4h and 24h p.L in anterior and posterior projections were performed to calculate whole body distribution. The recovery rate of the fragment in whole blood was 38.8% (5min), 24,4%(lh), 12.2%(4h) and 3,2%(24h). The recovery rate for the cell associated Tc-99m-fragment was 4%-6%(5min-60min). In-vivo infectious lesions could already be detected 1 h post injection. These results prove the low antibody binding to circulating granulocytes and a high in-vivo availability of the unbound antibody. In summary, this high in-vivo availabiltiy of the unbound Fab'fragment seems to aIIow a binding of the fragment lh p.i. to granulocytes in the loci and imaging of an infection independent from leucocyte migration. The diagnostic accuracy for imaging infection of a Tc-99m-label led antigranulocyte Fab'-fragment(NCA-90;IMMU-MN3) was prospectively examined in a multicenter study. Scintigraphy was performed in 53 patients(27m; 26f;age: 26-86 years) between 1-6 h and 24h p.i. after injection of 0.1-1.00 mg of antibody fragment labeled with 166-1036 MBq of Tc-99m In total, 39 infectious lesions were detected with histology, cytology, other imaging procedures, or by follow-up.38 patients were additionally examined with Tc-99m-HMPAO or In-111oxin labelled granulocytes within of one week of the MN3 study. Sensitivity, specificity and diagnostic accuracy of Tc-99m-MN3 was 92.3%,85.2% and 89.4%, of autologous leukocyte scintigraphy 86.7%,77.8% and 83.3%, respectively. The sensitivity was independent of the amount of the labelled antibody injected (0.1-0.5rag: 96.6%; >0.5-0.9mg:100%;> 0.9-1.00mg:71.4%). False positive lesions were detected in a periprosthetic calcification a frontal hyperostosis and two prosthetic hips which had loosened. H u m a n antimouse antibody (HAMA)could not be detected in any of the 13 patients 1 or 3 months postinjectioz In summary, Tc-99m-IMMU-MN3 is suitable for imaging infectious lesions and has diagnostic advantages over autologous leukocyte scintigraphy. The sensitivity is independent of the in jected antibody dose.HAMA could not be detected. Kairemo KJA, Korppi-Tommola T, Salo J0, Taavitsainen MJ, Rannikko S Depts of Clinical Chemistry, Radiology and Urology, Helsinki University Central Hospital Patients with verified skeletal metastases of prostate cancer were studied for pain relief by injecting 1300 MBq Re-186-HEDP (~ 1.07 MeV, 7 137 keV (9%), t~{ 89.3 h). These patients were studied quantitatively using gamma imaging (2-headed Picker Prism 2000 with Odyssey computer) at 4, 28 and i00 hours, and prior to therapy a quantitative bone scan with TC-99m-HDP. They have several multiple (>15) loci (I), superscan (lI) or a few (<15) strong uptakes (III). The lesions were analyzed using a conjugate view method (ROIs from AP and PA views, geometric mean and size of the lesion, std activity source) . The lesions were analyzed separately in skull (S) , vertebrae (V) , ribs {R) , pelvis {P) and extremities {E) separately using background subtraction (mirror technique. The skeletal Tc-99m-HDP-uptake at 4 h varied from 24.5% to 44.0 % ID, whereas the Re-186-HEDP-uptake at 4 h varied from 25.4% to 58.6 % ID. In lesions, eg.in a patient with 97 lesions, the uptakes of Tc-99m (at 4h)were as follows: S 0.030, V 0.073, R 0.29, P 0.051, and E 0.14 %ID/cm3; and with Re-186 (at 4h) S 0.034, V 0.068, R 0.35, P 0.053, and E 0.16 %ID/em3.The Re-186-HEDP-half lives in lesions varied from 41 up to 113 hours. The dissappearance rate from the skeleton was quite constant, the Re-186-uptake of ID was usually higher than that of Tc-99m. The highest uptake in a single solitary lesion was observed in IIl, being 0.36 % ID/cm 3, and the whole lesion was 11.2 % ID at 4 h. This data indicates that a proper quantitation should be performed in order to estimate the real dose delivered by palliative bone pain treatment because of large individual and interlesional variation. Reske SN, Fleischmann W*, Brecht-Kraug D, Schulte M, Kinzl L. * Department Radiology III and *Surgery III, University Ulm, Germany. Based on a highly stimulated glycolysis of activated leucocytes and macrophages, we examined performance of FDG-PET for detecting and defining anatominal extent of musculoskeletal inflammatory disease. In total, 25 patients (pts) with suspected chronic recurrent posttraumatic osteitis (19 pts) or spondylodiscitis (6 pts) were examined with FDG-PET in the fasting state 45 min after injection of 350-450 MBq FDG i.v. with an ECAT 931-08-.12 PET scanner (Siemens/CTI, Knoxville TN). Transverse, frontal and sagittal images were generated with an iterative reconstruction technique. In all pts, infection imaging was done additionally with a Tc-99m labeled monoclonal antigranulocytic antibody (TcNCAA) 4 and 24 hrs after injection of 350-450 MBq antibody i.v.. Presence or exclusion of active inflammation was determined by intraoperative and histological findings in 12 pts and by clinical follow-up in 13 pts. Focally increased FDG-uptake correctly identified 18 pts with active inflammation, whereas normal FDG-uptake excluded correctly active disease in 6 pts. Intramedullary osteitis, fistulas and paraosseal soft tissue involvement could only be differentiated by FDG-PET whereas TcNCAA only allowed the distinction of presence or absence of active disease. Active spondylodiscitis could not be diagnosed with TcNCAA but was clearly imaged as focally increased FDG-uptake in all 6 pts with PET. Sensitivity and specificity of FDG-PET -100% and 96% respectivelywere significantly superior to TcNCAA (61% and 86%, p<0.01, N=25). These first results indicate a significant potential of FDG-PET for detecting and localizing acitive musculoskeletal inflammatory disease. The specificity and potency of Pamidronate as an inhibitor of osteoc[astic bone resorption provides the rationale for its therapeutic use in osteolytic bone metastases. The mode of its action comprises: a) adsorption onto the surface of hydroxyapatite crystals in mineralized bone matrix, thereby reducing the solubility of the mineralized matrix and rendering it more resistant to osteoclastic resoption and b) impairment of the attachment of ostcoclast precursors to the mineralized matrix, thereby blocking their subsequent transformation into mature, functioning osteoclasts. On the other hand, Rc-186-HEDP exclusively aceumulatcs by chemisorption onto the surface of hydroxyapatite crystals of the ostcosclerotic osseous lesion. The efficacy of Pamidronate (dealing with the ostoolytic bone activity) and of Re-186-HEDP (dealin~ with the osteosclerotic bone activity) combined treatment was evaluated m 7 patients with mixed (osteolytie lesions, surrounded by osteosclerotie halo) bone metastases due to osteosarcoma (1 male aged 24 yrs), lung (3 males aged 37 to 57 years) and colon (1 female and 2 males aged 62 to 70 yrs) cancer. In all 7 cancer patients parallel to 1400+ 100 MBq Re-186-HEDP i.v. therapy [Mallinckrodt Medical B.V,, Petten] an anti-osteolytic treatment with Pamidronate [Aredia, Ciba-Geigy Ltd, Basel] was performed via i.v. infusions in a total monthly amount of 120 mg and for a three months duration. The follow-up period covered thirty weeks. The efficacy of the treatment was assessed by a) apam and performance questionnaire that the patientswere asked to complete daffy b) a CT and a bone density scan comparison of a randomly prcsclected osseous lesion before and 30 wccks after Pamidronate and radiolabelled Renium application. All 7 patients responded to therapy, The osteosarcoma patient became free of pain while the other 6 patients experienced obvious pain improvement. None manifested a flare response to treatment. All patients showed a definite decrease of platelets and absolute number of polymorphonuclear white blood cells up to the fourth week following treatment, Two out of 3 colon cancer patients underwent a whole blood transfusion. Combined Pamidronate and Re-186-HEDP therapy appears to bc very promissing for the palliation of painful mixed bone metastases. Bone metastases (BM) occur in 80% of patients (pts) with prostate carcinoma, the 2nd most common cancer in males and in 50% of patients with breast carcinoma, the most common cancer in females. Many other primary turnouts frequently metastasize to the skeleton and pain relief often requires long term narcotic analgesia when surgical, hormanal and chemoterapy treatment have failed. External beam radiotherapy may be effective for isolated BM but is difficult Io apply in multifanal disease. Strantium-89 localizes in osteoblastio BM. Its beta particles have sufficient energy to be therapeutically useful However, several reports show very different results in pain palliation, ranging from not different of a planebo response to 82% true response. This report details the results of a retrospective evaluation of 20 therapeutic administrations of 89Sr (about 4mCi iv) to 19 elderly, severely ill pts (1 retreatmont) with painful BM, not aleviated by any of the asual therapeutic means. 16 male and 3 female pie were entered, aged belween 54 and 82 years aid, with a moan age of 68,4±6,3 years. The primary tumor was prostate carcinoma in 16 pts, breast carcinoma in 2 and bladder carcinoma in 1. One female and 1 male pts were lost to follow-up; 4 aditional pie died in a short period (<3 months after 89Sr). The criteria for admission were (1) biopsy-proven tumor, (2) ggmTc-MOP bone scanning with evidence of extensive BM the week preceding therapy, (3) failure of prior canvantional therapy and (4) total WBC count >40(X)/mm3, total platelet count (TPC) >100000/ram3 and serum creatinine concentration 75%) from 5 min post injection on. To correlate the quantification data with cell proliferation, knowledge of metabolites contribution to the total tissue activity is a prerequisite. In this study using an animal model(rats), two independent pathways were followed. (I) The total activity in fast dividing tissue after i.v. injection of [methyl-lXC]TdR resp. [methyl-~C]thymine (first metabolite) was compared. For the rats injected with TdR, the tissue activity consists of labeled TdR and its metabolites. For those injected with thymine, tissue activity consists only of labeled metabolites. Depending on the model, the fraction of labeled metabolites yielded 3 to 30 %. (2) The liver was surgically clamped. Catabolism of TdR mainly takes place in the liver. Comparing the specific activity in fast dividing tissue in normal and in rats with "locked" liver function showed no significant difference between both series. The metabolite fraction was less than 10%. As conclusion, we can say that the major activity in fast dividing tissue consists of [methyl-x~C]TdR. Consequently, the PET quantification data can give information about cell proliferation and makes it possible to evaluate therapeutic techniques. Recently we described the selective synthesis and preliminary validation of [C-11]norepinephrine (NE) as a tracer for adrenergic neurons. Metaraminol is a NE congener which has a high affinity for the uptake-1 mechanism and, unlike NE, is not metabolised by MAO and COMT. [F-18] 6-Fluorometaraminol has previously been prepared from [F-18] acetyl hypofluorite (Mislankar et al., 1988) . However, this approach gave a product with too low specific radioactivity corresponding to a dose which is too high for PET studies in humans. In the present work, no-carrier-added preparation of [C-11]metaraminol was achieved by a selective condensation of [C-11] nitroethane with m-hydroxybenzaldehyde followed by reduction with Raney nickel. Chromatographic purification with reversed phase HPLC enabled the separation of the racemic erythroand three-forms of the product. [C-11] Metaraminol was prepared in 13-20% decay corrected radiochemical yield within 45-55 minutes with a specific radioactivity of 300-800 Ci/mmol (11-30 GBq/mmol). PET examination of racemic [C-11]erythro-metaraminol (META) in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. The radioactivity in the myocardium was more than 10 times higher than in adjascent lung tissue and more than 5 times higher than in plasma, In a pretreatment experiment using the NE reuptake inhibitor desiprarnine, radioactivity uptake in the myocardium was decreased by 80%. This observation demonstrates the specificity of META for the NE reuptake in the heart. The metabolism of META, determined in plasma by HPLC, was rapid. The fraction of total radioactivity representing META in plasma was 14% at 6 rain and 8% at 34 rain. High specific radioactivity META should be useful as a radioligand for imaging of cardiac sympathetic neurotransmission in the human heart. Pargyline is a MAO-B inhibitor which has been labelled with 1-123 in order to perform SPECT studies (J Nucl Med, 1993 34; 5, 335p) . For assessment of MAO distribution in brain by PET, Br-76bromopargyline (N-2-bromobenzyl-N-methylpropargylamine) was prepared from the iodinated analogue using heteroisotopic exchange. The Cu+ assisted substitution reaction between nca radioactive bromine and the cold iodine of iodopargyline takes place at 165°C using gentisic, ascorbic and citric acids as reducing agents. A RP-HPLC " purification gave Br-76-bromopargyline in a 75% radiochemical yield with a specific activity of 20 MBq/nmol. The inhibitory activity of 2-bromopargyline was assessed in vitro by measuring its potency to inhibit the MAO activity in rat brain homogenates. The IC50 values toward MAO-A (26 nM) and MAO-B (3.3 riM) demonstrated that 2-bromopargyline possess a good selectivity for MAO-B and a higher affinity than pargyline itself (ICso MAO-B= 20 riM). In rats, biodistribution kinetic studies showed a high uptake (0.5% ID/g) of Br-76-bromopargyline in brain. Using ex vivo autoradiographic studies, a preferential localisation of the radiotracer was observed in the pineal gland and the thalamus, brain structures which are known to possess high concentrations of MAO-B. These preliminary results suggest that Br-76-bromopargyline could be a useful radiotracer to study, by PET, the variation of MAO-B activity in neurodegenerative pathologies where monoaminergic neurotransmissions play an important role. For PET studies of the monoamine uptake sites, 13-CIT and its fiuoro analog ([3-CFT) have been labeled with C-1 t. To study the role of the halogen in the selectivity of the tracers for the dopamine reuptake sites, we have labelled the bromo analog I3-CBT [213-carboxy-3l]-(4bromophenyl)-tropane] with Br-76 (T 1/2 =16h). Br-76 I3-CBT was prepared either by electrophilic substitution from the tributyl-stannyl derivative with Br-76 using peracetic acid as oxidant or by nucleophilic substitution using 13-CIT and a Cu + assisted bromodeiodination exchange. Polar by-products were eliminated by SPE using a C18 cartridge and Br-76 13-CBT was purified by RP-ItPLC Using the two techniques, the radiotracer was obtained in 80% and 60% radiochernical yields, respectively, with specific radioactivities -20 GBq/gmol. PET imaging of Br-76 13-CBT biodistribution in baboons demonstrated a rapid and high uptake in the brain (5% ID) and lh after injection, the radioactive concentration in the striatum reached a plateau (0.13% ID/g) that remained constant for 4 h. No specific uptake in the cortex was observed. Due to the constant wash-out in the cerebellum, 4 hours after injection, the striatum to cerebellum ratio was 10. In a baboon with unilateral MPTP induced substantia nigra lesion, the uptake in the diafferented striatum was reduced by 50%, a value similar to that obtained using C11-13-CFT. These results suggest that Br-76 13-CBT has the potential of being developed as a useful PET radiotracer for imaging monoamine uptake sites in pathological conditions. A In order to study this relation, we assessed sympathetic activity, by measuring [123I]-MIBG activty after intravenous injection, in an animal model where these disorders exist either simultaneously or separately. In male Wistar Kyoto rats (WKY) and in spontaneously hypertensive rats (SHR), diabetes was induced at the age of 12 weeks by a single injection of 60mg/kg streptozotocin (STZ) i.v. At the age of 20 weeks the rats received 10~tCi/kg body weight [123I]-MIBG. Thirty minutes after injection of [ 123I]-MIBG, blood samples were taken to measure noradrenaline levels (NA) and the rats were sacrificed. Organs were weighed and total radioactivity wag established. Two weeks later B-adrenoceptor (13-AR) density in the heart was measured. NA levels, heart/lung radioactivity ratios and B-AR densities were compared as listed in the Captopril-induced changes of 99mTc-MAG3 renal scintigraphy (CRS) were evaluated in 58 hypertensive patients highly suspected of having renal artery stenosis (RAS) and arteriographicaUy controlled. Eleven showed BR, 3 of which twice (before and after percutaneous transluminal renal angioplasty (PTRA)). In order to distinguish false from true positive BR, changes in these 14 BR were compared with arteriographic data. Arteriography showed renal artery stenosis (RAS) (bilateral in 2) in 9 patients and no renal artery stenosis in 5. Chronic renal failure (plasma creatinine >__ 129 ~tmol/l) was present in 9/11 and peripheral artery disease in 8/11 patients. A by kidney and a by patient analysis of time to peak (TP), residual activity (RA) at 24 min, mean parenehymal transit time (MPTT), split renal function (SRF) and of renographic pattern grades (RPG) were done in these 14 BR. In 8/9 patients with RAS and in 1/5 without RAS, the right to left differences in TP and RA changes were > 7 min. and > 7%. These changes were more marked in unilateral RAS than in bilateral RAS. According to RPG the right to left differences in scores changes were >1 in patients with RAS and null in patients without RAS. Surprisingly the largest changes were not located to the stenosed kidney in 6/8 patients. MPTT and SRF were not significantly different in patients with or without RAS. In patients with BR in CRS : i) Asymmetrical BR may help to detect RVH. The capability to differentiate bilateral from unilateral RAS still remains to assess in a larger group, ii) Although asymmetrical BR is often present in patients with RAS the largest eaptopril-induced changes were not always localized to the stenosed kidney in our short series. Antimyosin imaging is routinely used for detection of rejection in heart transplant (HTX) patients. Repeat rejections reduce the patients' long term prognosis. Correlation of myocardial cell damage as detected by antimyosin and serial evaluation of heart function with stress radionuclide ventriculography (RNV) was the purpose of this investigation. Patients: In 20 patients, transplanted between 7/86 and 8/92, In-111 antimyosin (AM) scans were applied (142 scans, mean 7.1/patient, 530 months overall follow-up since HTX, mean 26,5 months, mean every 3.7 months/patient). For detection of rejection a heart-to-lung ratio (48 h p.f.) of >1.5 was set. All ratios < 1.5 were considered negative. Serial RNV was applied in all patients (2-11 studies/patient) at rest and under tread mill stress (25-75 W). Results: 10 patients had positive AM scans ( maximum values range 1.6-1.98, mean 1.8) and at least 1 rejection episode (1-3 episodes, mean 1.85) and 10 patients were negative (max. values 1.22-1.5, mean 1.41). Regarding RNV, even close to EMB proven rejections, normal rest EF values were obtained. In long term follow-up, in both groups rest global EF decreased, but stayed in the lower normal range (>50%). Decisively, stress RNV clearly seperated both groups. 7/10 in the AM negative group maintained a normal stress EF increase, 1 no stress done, in 2 EF decrease. Of the AM-positive group 8/10 demonstrated a global EF decrease under stress with normal rest EF values. Conclusions: Whereas antimyosin is a reliable screening tool for detection of HTX rejections, radionuclide ventriculography at rest is unreliable for evaluation of acute rejection episodes. Stress RNV is highly significant for evaluating loss of heart function in patients with rejections. The aim of this study was to calculate left ventricular volumes by tomographic radionuclide ventrieulography IV.) and to correlate with data obtained from angiographic studios. 20 patients [18 male and 2 female) with mean age 57,q years +_ 10 were divided in 2 groups : group T included g patients with normal coronary angiogram [6 pts with normal ejection fraction, 2 pts with aortic valvular disease and 1 pt with dilated cardiomyopathy) ; group 2 included 11 patients with significative coronary stenosis and altered ejection fraction : anterior M.I. [q], postero-inferior M,I. Primary cardiac tumors are less common. It is of potential interest to distinguish between malignant and benign tumors in order to select the best therapeutic strategy. We report our preliminary experience in combined PET and MR imagingperformed in 8 patients with primary cardiac tumors and in 3 patients with mediastinal tumors for evaluation of operative strategy. MR Investigations were performed on a Picker 1.5 T HPQ system using T1weighted spin-echo, segmented k-space, field-echo and bright blood fieldecho sequences. The investigation Was repeated after Gd-DTPA infusion. In 2 patients with large cardiac tumors proton-MR-spectroscopy was attempted, Al/patients underwent leFDG PET before and after glucose loading. Tracer uptake, distribution, and glucose metabolic rates of the tumor and of the surrounding myocardial tissue were evaluated. PET and MR images were also matched by using the software developed in our center. The results were then compared with those from transesophageal echocardiography (TEE), transthoracic echocardiography (TTE), CT and with intraoperative and histologic findings. MR Imaging demonstrated excellent delineation of tumors of the heart andsurrounding structures superior to TTE, TEE and CT due to better soft tissue constrast. In all patients but one the preoperative prediction of the resectability of the tumor was achieved correctly. Compared to TEE, MRI failed in most cases to detect tumorous lesions smaller than 0.5 cm, particularly those which involved the papillary muscle and those involving the right ventricle. Slight improvement in the detection of such small lesions was achieved after Gd-infusion. Tumor infiltration and expansion detected in MRI correlates well with enhanced tumor glucose metabolism. These can help in the evaluation of tumor dignity. In 1 Patient with an enlarged hemangioma in the right ventricle with significant obstruction of the outflow tract, the combined PET and MR images were falsely interpreted as well vascularized malign sarcoma of the heart. However, as confirmed by intraoperative findings, the non-resectability of the lesion was correctly diagnosed. It is concluded that combined PET and MR imagin 9 might be a valuable tool for the evaluation of operative strategy of cardmc and mediastinal tumors. Motion artifacts combined with a strong signal from fat resulted in very poor spectra with no diagnostic advantage. has not yet been reported. We evaluated the value of IIIIn-HIG for diagnosing AL in 35 patients (mean age 59±4.7) with ultrasonographically suspected AL in the carotid arteries. A comparative study between lllIn-HIG and 125I-LDL uptake in AIL was also performed in cholester01-fed rabbits. Four hours after iv injection of 500uCi IIIIn-HIG ap images (500000 counts/frame) of the neck were obtained with a gamma camera. The HIGuptake was also continuously monitored with detectors placed over the carotid arteries and a background region and time-activity curves were analysed. After injection of 10uCi IIIIn-HIG and 1251-LDL, the HIG-entry into aortic segments was evaluated in animals. In order to compare the long term prognostic value of left v e n t r i c u l a r ejection fraction (LVEF) routinely determined by single plane Xray angiography and by equilibrium radionuclide angiography (RNA), a 5-year follow-up period was obtained in 103 consecutive pts (99 men, 54±8 years) with Q wave MI, who had X-ray and radionuclide LV-angiography, and who were initially treated medically. X-ray LVEF, determined by cardiac catheterization (area-length method on a 30 ° RAO) was higher than that determined by RNA (manual method on a LAO) in the overall population (p<.05). BUt the difference was marked for pts with anterior MI (n=51) (46±13% vs 39±14%, p<.001) and absent in the others (47±13% vs 49±10%, NS). When we compared pts with cardiac death (n=13) to those without death, cardiac surgery or angioplasty (n=79) during the 5-year of follow-up, MI location was more frequently anterior (85% vs 47%, p<.02) and both X-ray and RNA LVEF were lower. However, the difference between the 2 groups was slight for X-ray LVEF (41±12% vs 48±12%, p<.05) and much more marked for RNA LVEF (32±12% vs 46±12%, p<.001). Compared with single plane X-ray angiographic determination, LVEF calculated by RNA appears to be a better long term predictor of cardiac death after Q wave MI. This might be related to improved assessment of LV function in anterior MI. Can the immunogenicity of radiolabeled routine antibodies be reduced by immunosuppressive treatment at nontoxic doses? The immunogenicity of murine antibodies is one of the main limiting factors of immunoscintigraphy and radioimmunotherapy. Their replacement with human or humanized antibodies provides a partial solution to this problem. However, in the organ transplant field, where anti-T-lymphocyte murine monoclonal antibodies have been used for more than 10 years, an alternative approach to reduce sensitization frequency consists in associating conventional immunosuppressants with monoclonal antibody treatment protocols. Thus, we tested low-dose, short-term immunosuppressive treatment in 14 patients injected with 1 mg of F(ab')2 fragments of 0C125 antibody for scintigraphic detection of recurrences of ovarian carcinoma. We administered 15 mg/day of prednisolone and 3 mg/kg/day (but not more than 150 mg/day) of azathioprine, for six consecutive days (beginning 2 days before immunoconjugate injection). The appearance of anti-OC125 human antibodies was monitored by a solidphase immunoenzymatic technique (ELISA). Three of these 14 patients (21%) developed human anti-mouse antibodies (HAMA), whereas in a control group receiving the same preparation of F(ab')2 fragments (without immunosuppressive treatment) 7/22 subjects (32%) developed HAMA (nonsignificant difference). Thus, this type of immunosuppressive regimen did not significantly reduce immunization against the xenogenic protein. The possibility of using other types of short-term (<10 days) immunosuppressive treatments in association to immunoscintigraphic and radioimmunotherapeutic protocols will be discussed. Tc-99m is a nearly optimal rediolabel which to date has been underutilized in immunoscintigraphy. We examined the safety and performance of Tc-99m labeled anti-tEA Fab' monoclonal antibody (ImmuRAID-CEA) in non-small cell lung cancer. In a multicenter trial, fifty four patients were studied (42 male, 12 female; ages 40-93 yr.) who had primary operable (19), primary inoperable (7), occult (9), metastatic (15) or recurrent (4) disease. The injected dose was 20-30 mCi Te-99m labeled to 1 rag protein. Planar and SPECT imaging was performed at 4-8 and 18-24 hr in 44 patients and at 15-18 hr only in 10 patients. There were no clinically significant adverse reactions. There were four minor and transient alterations in biochemical and/or hematologic indices. In 27 patients tested at 4-6 weeks or 3 months, human anti-mouse antibody (HAMA) assays were negative by Immustrip® HAMA fragment kit. Overall sensitivity (Sens) for tumor detection on a per patient basis was 90%, accuracy (Aco) 85% and positive predictive value (PPV) 94%. On a region basis Sens was 80%, Ace was 84% and PPV 83%. Sens in the chest on a per lesion basis was 69% and 88% in the liver. Prominent blood pool activity was noted on the early images but improved target to background ratios with lower count rates were present on the delayed images. A negative scan confirmed equivocal studies as true negative in 5 patients. Foci of tracer uptake at previously unsuspected sites were observed in 24 patients. Of these, cancer was confirmed in iI, not confirmed in 2, and remains indeterminate in ii. ImnluRAID-CEA immunoscintigraphy has proven safe and has potential utility in the depiction of tumor extent in non-small cell lung cancer. Whole-body PET correctly demonstrated 27 metastases in the lung, brain, pancreas, nasal activity, cutis and subcutis and in lymph nodes. The sensitivity of all metastases larger than the spatial resolution of the PET-system (> 5 ram) was 100 %. Two cutaneous metastases, measuring approximately 3 mm, did not show an increased FDG-uptake, the overall sensitivity was therefore 96 %. PET correctly excluded malignancy in 4 cases, where suspicious lesions were found with conventional crossectional imaging modalities but later ruled out by fine needle biopsy. In summary our data demonstrate the clinical potential of whole-body FDG-PET for the detection of metastising melanoma. The first p a t i e n t was t r e a t e d with p a l l i a t i v e radiotherapy, the s e c o n d with s u r g e r y a i m i n g for a cure. In one of the eight p a t i e n t s with a n e g a t i v e scan, the s u b s e q u e n t c l i n i c a l c o u r s e r e v e a l e d a p a p i l l a r y t h y r o i d carcinoma. In the r e m a i n i n g seven p a t i e n t s a p r i m a r y lesion was n e v e r found. In all p a t i e n t s the The specificity was similar for beth agents: InLLS 83% and Ga-67 80%_ InLLS, however gave dearer images than Ga-67 for the evaluation of abdominal and hilar uptake. In 4 further patients with NHL, InLL$ showed no accumulation in known lymphoma lesions. We could find no abnormalities of T cell function in these 4 patients, as shown by mitogen activation, ratio of T cells to B cells, or ratio of OK-r4 to OKT8. We also could net prove any associated abnorrnali~ss of lymphocyte uptake in adjacent inflammatory changes in these patients' biopsy specimens. On the contrary, in 9 patients with inflammatory diseases, lymphocyte migration to inflammatory loci correlated with T cell activation by mitogen. We suggest that anergy of lymphocytes in patients with NHL is due to more complicated factors. In 35 patients with NHL, 4 were negative with InLLS and in 29 patients lymphocyte migration was observed only in the 24 hr images. InLLS showed uptake in tumor lesions on beth 4 and 24 hr images in only 2 patients w~h NHL, but in all 4 patients with HD. NHL is distinguished by this slow accumulation from inflammatory diseases and HD which showed early accumulation. The Fab' of this IgGl MAb has been labeled by a direct, 1-step method, with Tc-99m, and examined as a noninvasive, simple imaging procedure for diagnosing Pc infection in immunocompromised patients, using 1 mg of MAb labeled with 25-30 mCi Tc-99m and injected i.v. Planar images at 24 h proved to be optimal, and revealed a high rate of accuracy in disclosing Pc pneumonia in a series of HIV-patients. Results correlated with sputum and bronchoalveolar cytology, Ga-67 scans, and chest roentgenograms in 15 assessable patients showed 6 true-positives, and 7 true-negatives, indicating a sensitivity and specificity of imaging of over 85%. In an additional 3 patients, the Pc MAb disclosed pneumonia whereas a control, similarly prepared, anticancer MAb Fab' did not show specific accretion. These results suggest that this organism-speciflc MAb may be of use in the rapid and specific diagnosis of Pc infection in immunocompromised patients. The medium B2M concentration in patients with CDC II or III category was 3.08 mg/I and in patients with CDC IV category was 4.07 mg/l. Significant differences were found between 2 groups (p =0.0007), The medium B2M concentration in HIV-patients was 1.81 mg/I and in HIV+ patients was 3.28 mg/l. Significant differences were found between both groups (p <0.000001 ), Besides, in a subgroup of 50 HW+ patients without zidovudine therapy we studied the relation between serum B2M levels and CD4 lymphocyte count. B2M concentration was significantly and negatively correlated with CD4 count (r=0.348, p =0.00083). In view of the importance of an early identification of individual haemophiliac patients with high risk of fast progression to AIDS, our preliminary results seem support the idea that serum levels of B2M adds important prognostic information to CD4 count in determining the risk. We are now carting out a prospective study in these kind of patients in order to predict CD4 cell deplection and disease progression and assess response to treatment. More data are therefore needed about the prognostic significance of serum B2M levels. Thirtythree injured solidiers were surgicaly treated because of pierce wounds of extremities. Treatment was either osteosinthesis or external fixation. Two to 4 weeks post treatment clinical signs of osteomyelitis appeared. X-ray was negative in all patients. Three-phase bone scan was performed in order to establish diagnosis. Bone scan was positive in all patients. For ii patients only bone scan was sufficient for deeission of further treatment. In 22 patients Ga-67 or 99mTc-nanocoll or both examinations were performed on surgeon, s request. In 2 patients out of 5 with additionaly Ga-67 scan, Ga-67 scan showed more lesions than it was seen on bone scan. In 3 patients out of 5 with additionaly 99mTc nanocoll scan, 99mTc nanoeoll scan showed more lesions than it was see on bone scan. In 12 patients with positive bone scan and negative or unclear Ga-67 scan 99mTc nanocoll scan was performed. In 5 out of 12 patients 99mTc nanocell scan establish diagnosis in others confirmed finding on bone and Ga-67 scan. Our results showed that in majority of cases 3-phase bone scan was sufficient for diagnosing of osteomyelitis caused by war injuries. In selected cases where bone scan was not sufficient for diagnosis and decission of treatment 99mTc nanocol was more sensitive than Ga-67. In our experience three phase bone scan is method of choice for diagnosing of osteomyelitis in war situation with a io~ of causalties. Chronic bone infection (CBI) is best imaged with In-lll granalocytes(IeG). Since radiolabelled granulocytes(RLG) are taken up by the bone marrow (BM), interfering with the interpretation of the granalocyte scans, a colloid scan is usually necessary to define RM, the distribution of which is significantly altered after surgery. R i G uptake in BM as early as 1 hr after injection is more evident when granulocytes are labelled with Tc-99m HMPAO, and suggests granulocyte margination, which could be used to define BM. If this assumption is true, then, labelling of granalocytes with both Tc-99m and In-111 and using the early Tc-99m signal to define BM and late InLG signal to show the migration to CBI would avoid the need for a colloid scan.The aims of this study were,therefore, 1) to establish the nature of early RLG uptake in BM, 2) to describe a new technique of labelling granalocytes with both In-111 and Tc-99m t-IMPAO in order to exploit this uptake, 3) to verify the functional integrity of these granulocytes, and 4) to predict the feasibility of this technique for the diagnosis of CBI in humans. Fifty seven patients were studied in 2 parts. In the first part, we retrospectively quantified InG uptake in BM, spleen (Sp), liver (iv) and 3 different types of inflammatory lesions (Le) by comparing the early and late Le/BM ratio with Le/Sp and Le/Lv ratios. In the prospective second part, we labelled granulocytes with both In-Ill and Tc-99m HMPAO, studied their kinetics in Sp, Lv and BM in 14 patients with painful prosthetic hip, and compared this technique with colloid BM scan in 9 patients. We showed that 57% of the BM signal from InG at 3 br was due to marginated cells. The corresponding values for Sp and Lv were 71% and 47%, respectively. In the second part, cell labelling efficiency was 38.6%+12 and 62.6% + 14 for Tc-99m-HMPAO and In-Ill, respectively. Granulocyte activation, determined as the percentage of cells showing shape change, and recovery of double labelled granulocytas were similar to those previously published for single labelling. We conclude that granulocytes can be labelled with both In-Ill and Tc-99m without cell activation or damage, and double labelling of granulocytes appears to be a promising tool in the diagnosis of CBI, using the early Tc-99m signal to define BM and the late In-Ill signal to demonstrate migration to CBI. B~SOn,qer~ U. Hoppe*, H.-J. Deutsch*, P. Theissen, U. Sechtem*, E. Erdmann*, H. Schicha. In case of congenital heart disease (CHD) an accurate depiction of anatomy and function of the heart is a main diagnostic issue. As could be shown this is To assess myocardial energy metabolism in aortic valve stenosis before valve replacement, 10 patients with severe aortic valve stenosis (effective aortic orifice < 0,8 cm2; pressure gradient across the aortic valve _> 70 mm Hg) were examined on a Philips 1,5 Tesla imaging / spectroscopy magnetic resonance system using a surface coil and Gyroscan / ISIS software. 6 patients had a hypertrophic left ventricle but normal ventricular contraction (group A), 4 patients had a dilatation of the left ventricle (LV) (left ventricular enddiastolic diameter (LVEDD) -mean: 59.4 + 3.6 ram) and clinical sign of heart failure (group B). The PCr-/13-ATPratio of the myocardium was compared to those of 15 healthy volunteers. To minimize the influence of blood-ATP, all spectra were acquired at end-systole. The cube-shaped volume of interest was placed after performing gradient-echo magnetic resonance imaging into the apical-septal area of the myocardium. Spectra were evaluated by an iteration program and corrected for T 1-effects and blood contamination. Mean PCr-/13-ATP-ratio in group B was reduced from 1,79 -+ 0,21 (healthy volunteers) to 1,27 +, % 0,22 (p = 0,01 -unpaired t-test). Patients (A) without elevated LVEDD had a PCr-/[3-ATP-ratio similiar to those of normal controls (A: 1,87 _+ 0,22; p = 0,45). The reduced PCr-/13-ATP-ratios in patients with severe aortic stenosis and elevated LVEDD is in agreement with the reduced PCr-/[3-ATP-quotient observed in in vivo 31-P-MRS studies on patients with cardiomyopathy. It is likely caused by structural abnormalities of the LV-hypertrophy after LV-dilatation and decreased total creatine levels and/or altered creatine kinase activity. To what extend a decrease of the PCr-/[~-ATP-ratio is a predictor of a beginning heart failure must be assessed by further investigations. NMR fields with both wide bore and high field strengths have become available, allowing the application of magnetic resonance spectroscopy (MRS) in larger mammalian organs. Energy status of these organs as determined by P-31-spectroscopy will depend on the treatment following explantation. Therefore, the aim of this studie was to test different preservation protocols after explantation in a liver model. 30 cadaveric porcine livers were harvested from the slaughterhouse after 11.3 + 0.8 rain of warm ischemia. After preparation of the right lobe livers were treated for storage in 5 different protocols: after sudden reperfusion with homologous blood and subsequent perfusion with cold collins solution, livers were stored at 4 °C for 1-2 h (No. 1) or 4-6 h (No. 2). Protocols No. 3 and No. 4 were identical, except for the omission of blood perfusion. Protocol 5 (No. 5) equaled No. 4, but storage time was extended to 24 h. MRS was performed using a 4.7 T/40 cm diameter system with 60 ° pulses at 81 MHz and subsequent Fourier analysis under identical conditions for all five protocols after reperfusion with warm homologous blood. During perfusion, index of [3-ATP and inorganic phosphate (13-ATP/Pi) was compared at 20 and 80 rain, respectively. Medians (n=6, each protocol) of y-ATP/Pi are given in the .082 Additional perfusion with warm blood decreases recovery of ~-ATP. Increase of storage time from 1-2 h to 4-6 h increases recovery of [3-ATP, while storage time of 24 h worsens I~-ATP recovery. In conclusion, in explanted liver best preservation is received by cold storage for 1-2 h in collins solution only, possibly due to reduced thrombosis. Given the lack of suitable common internal markers, the registration of cardiac MR and P E T images can be performed using external reference markers. A fundamental assumption of the method is that there is no relative movement between the markers and the anatomy of interest, namely the heart. A number of potential types of movement have been simulated with a view to determining the accuracy of the method. The lack of ionising radiation makes MR an ideal technique for repeated measurements to determine dominant error sources. Initially, however, the non-linearity of the MR gradient system must be determined. Fortunately, the non-linearity can be determined and corrected using software; we have performed this. Three reference markers containing cod liver oil were then placed on a volunteer. The plane containing all three markers was found uslng a fast field echo sequence. The "3-marker" plane was found after simulating a number of different types of patient movement. The anatomy within the plane could thus be compared directly. We have used MR to investigate movement and position of the heart relative to the markers caused by the following: (a) gross patient motion; (b) motion caused by raising and lowering of the arms; (c) sliding around on the patient couch in between measurements; Id) the effect of a full stomach; and (e) imaglng on consecutive days. Additionally, we comment on the problems of matching gated MR images with non-gated PET images. MR and PET images registered using the external marker method will be presented. Wide-bore NMR fields with high field strengths have become available, allowing the application of magnetic resonance spectroscopy (MRS) in larger mammalian organs. Energy status of organs may be determined by P-3 !-spectroscopy may determine enrgy ststus of these organs, which will be dependend on the treatment following explantation. Therefore, the aim of this studie was to test different preservation solutions in a liver model. 35 cadaveric porcine iivers were harvested from the slaughterhouse after 10 rain of warm ischemia. After preparation of the right lobe and cooling down by perfusion MRS was performed to examine the energy phosphate pattern as an index of viability using a 4.7 T/40 cm diameter system with 60 ° pulses at 81 MHz and subsequent Fourier analysis. Investigation was carried out as follows: Cooling with Collins (COL) solution (n=17) or Bretschneiders (BRET) solution (n=18), MRS, reperfusion with warm blood for 80 min to allow 13-and y-ATP-peak to recover completely, MRS, re-cooling with Collins solution or Bretschneiders solution and MRS for 240 rain. Vanishing of y-ATP-peak was quantified by the index y-ATP/MDP-standard. Time axis of re-cooling was normalized to index maximum. In-vivo phosphorus spectroscopy (31-P-MRS) has the potential to determine energy/phosphate metabolism noninvasively. In order to evaluate metabolite concentration in h u m a n organs with blood contamination (e.g. heart) by 31-P-MRS, a correction factor (CF) for the influence of blood-ATP is necessary. Since 2,3-diphosphoglycerate (DPG) mainly occurs in blood and has a constant relation to blood-ATP, quantification of the DPG/ATP-ratio may be a reliable CF for blood contamination e.g. 31-P-MRS of the heart. To assess a CF, fully oxygenated whole blood (4 ml) of 9 healthy volunteers were examined on Bruker 4.7 Tesla spectrometer. Quantitative in-vitro 31-P-NMR spectra were obtained spinning (10 rotations per see.) at 4°C for 4 hours (4000 scans) using a repetition time of 3 sec and 1-H-pulse decoupling. Chemical shifts were referenced to 85% H 3 P O 4 using the chemical shift of internal methylene diphosphonate (1 ruM). To keep the whole blood homogeneous, spectra acquisition were carried out using a permanently rotating glas stirrer. Iatrogene cell destruction could be excluded from microscopic analysis and erythrocytes counting of the blood samples, which were performed previous to and after each measurement. Spectra were evaluated by an iterative deconvolution process, the CF was obtained using the DPG/c~-ATP-ratio. The m e a n c o n c e n t r a t i o n in h u m a n w h o l e b l o o d of 2,3diphosphoglyeerate is 1,92 + 0,32 mM, of c~-ATP is 0,52 _+ 0,08 raM, inorganic phosphate is 0,71 -+ 0,12 raM. Mean DPG/ATP-ratio of whole blood is 3,84 + 0,84. This study shows, that quantitative determination of high energy phosphate in human whole blood is possible by MRS. To assess a CF for blood contamination in in-vitro, it is sufficient only to evaluate the mean DPG/ATP-ratio, because there is no dependence of the DPG/ATP-ratio on the erythrocyte count or hematocrite in whole blood. G.Sarti*, S.Lazzari*, P.Riva ~ *Health Physics Department and ^Nuclear Medicine Department, "Bufalini" Hospital, Cesena Italy In radioimmunotherapy a dosimetric approach at tissue level is required to analyse the effects of radionuclide distribution. We have studied the differences in therapeutic effect for the radionuclides commonly used in radioimmunotherapy (I131 Y90 Cu67 Re186 Re188 Sm153) versus various tumours wich differ in size, thikness and shape. A MonteCarlo code (EGS4 -PRESTA) has bean employed to simulate the emission and to transport the beta and gamma emission in human tissue. We have calculated the kernel scaled beta dose in water in order to evaluate the dose distribution around a source point. We have assumed idealized geometries for both the radioactive source volume and the target volume of tumour of our patients and we have calculated the fraction of absorbed dose with a spatial resolution of I0-i00 Vm and with i00.000 histoires simulated . . . old woman by surgery, radmtmn and racholo~me therapy (10 single applications ranging from 3300 to 3840 MBq). She was asked to prevent a pregnancy. Nevertheless, in the course of radioiodine therapy an attended gynaecologist found the woman pregnant in the 24 m week of gravidity. Consequently radioiodine has been administered during the 2 °a and the 22 nd week of pregnancy, each time 3700 MBq. The ovarial dose resulting from the radioiodine administrations before pregnancy was estimated to 2200 mGy (220 rd), the foetal doses resulting from the two administrations during pregnancy to 250 mGy (25 rd) in each case, and the foetal thyroid dose to between 90 Gy (9000 rd) and 900 Gy (90000 rd) for the 2 nd therapy during pregnancy. Because of the risk of malformations this pregnancy was interrupted taking the recommendations of the so-called Danish model as a basis for the decision. The foetus was studied with regard to possible consequences of radiation exposure by pathologico-anatomical cytogenetic and radiobiological methods. In the foetus the most important changes were found within the thyroid gland (atrophy, sclerosis, subcapsular interstitial fibrosis, necrobiosis of follicular epithelial cells). On the other hand, analysing the karyotype using dermal fibroblastic cell cultures, no radiation induced chromosomal aberrations were seen. The results of these studies present in detail give useful information on effects to be expected as a result of radioiodine application during certain periods of pregnancy. They might help to extend the radiobiological knowledge with regard to the foetal period• Post-production neutron activation of an intact pharmaceutical preparation is a labelling technique of interest for specific research purposes. However, in-vivo use is limited by the complex dosimetry. We report on our experience with an 170Eroxide enriched enteric coated pancreatic enzyme preparation used in dual isotope gastric emptying studies. Other labelling techniques were considered inappropriate because of possible interference with the pH-dependent release of the pancreatic enzymes, which was measured simultaneously. Neutron activation of biological materials results in many radioactive isotopes besides 171Er. This affects scintillation camera operation and adds to the radiation dose. The activation yields, half IEes, and radio-toxicity vary strongly. Therefore, all these radiocontaminants (RC) must be taken into accmmt Within the limits for adequate imaging, the ratio of committed dose equivalent due to 171Er and the total committed dose equivalent should be maximised. This ratio varies with the interval between neutron activation and ingestion (IAI). This ratio and the dose are most easily calculated when the ALI (ICRP 61) is used as a common denominator. After optimisation, 171Er accounted for 83% of the committed dose equivalent of 0.5 rosy per MBq of 171Er. The isotopic content was verified through instrumental neutron activation analysis. Some pitfalls are : -23Na is omnipresent in biomatefials; 24Na emits high energy photons that penetrate conventional high-energy collimators and interfere with image quality; -isotopic enrichment (in our case 97.9 % 170Er) does not preclude significant amounts of other lanthanides (i.e. in this case 5400 ppm of other lanthanides); -many RC may result, each with its own unique physical and biological properties (i.e. beta-emitters such as 32P and 35S); -RC may be present in a chemical form for which dosimettic data is not available; -for trace contaminants very. large batch-to-batch variations must be anticipated (i.e. Lu varying from < 10 to 700 ppm); -the neutron beam energy, spectrum may include epithermal and fast neutrons, resulting in increased activation yields for some elements; If these pitfalls are taken into consideration, neutron activation of isotopically enriched pharnmcentieals is a suitable labelling technique that does not interfere with specific galenic properties. The monoclonal antibody (MAb) 425 (produced by the Wistar Institute, Philadelphia) binds to a protein domain of the external part of the epidermal-growth factor receptor as overexpressed in human high grade gliomas. MAb 425 is currently being used in a therapeuticclinical phase II trial with promising results. The low accumulation in intracerebral tumors has partly been attributed to a still intact bloodbrain barrier (BBB) and/or blood-tumor barrier. In a recent autoradiographic study, Leukotriene C4 (LCT4) has been demonstrated to open selectively the blood-tumor barrier of intracerebral tumors, resulting in an enhanced uptake of C14-1abeled gamma-aminobutyricacid (GABA). The aim of this study was to investigate the effect of LTC4 on the accumulation of MAb 425 in xenotransplanted nude rats. Nude rats were stereotactically transplanted with the human glioma cell line A1235 in the right frontal lobe. Eight days later, rats received an infusion of 1-125 labeled MAb 425 (300 ,uCi) via the carotid artery. Prior to the MAb, rats were injected with LTC4 (4 ,ug) or saline via the same route. Animals were sacrificed 24 hrs later and radioactivity distribution of tumor, normal brain, and several other organs were determined. Our biodistfibution data showed that LTC4 treated animals showed a 2.7-times higher MAb accumulation in the tumor as compared to the controls. No statistical significant differences were found in the ipsilateral and the contralateral normal brain tissue of LTC4 treated animals as compared to control animals. These preliminary data demonstrate that LTC4 is able to enhance selectively MAb accumulation in intracerebral tumors. This effect is probably due to opening the blood-tumor barrier. Further studies are necessary to evaluate the therapeutic implications. The aim of the present study was to evaluate the effect of unlabeled antibody on the biodistribution and pharmacokinetics of 111-In PAP-MoAb (prostatic acid phosphatase monoclonal antibody). The human purified PAP was used in the preparation of a spesific MoAb. DTPA-derivates of the antibody F(ab')2-fragments (1 mg) were labeled by 185 MBq l l l -I n chloride, l l l -I n was chelated by the DTPA-moiety attached to the antibody fragment. The unlabeled antibody was given slowly intravenously (30 min) in a randomized fashion tO invidual patients at three different doses (0 rag, 40 mg and 80 mg/100ml) diluted with physiological saline to 100 ml. The labeled MoAb was injected 60 min after initiating the unlabeled MoAb. Until now 15 patients have been imagined. Biodistribution and pharmacokinetics of l l l -I n PAP-MoAb in semm was evaluated using the sum of 2 and 3 exponentials. Results indicated that the 3 exponential model was more reliable. The apparent final halflife (>20h postinjection) was 10 h for the patients receiving no unlabeled antibody. For the patients given unlabeled antibody the apparent final halflife for l l l -I n PAP-MoAb was 24 h in serum. The liver to blood ratio of the patients with no unlabeled antibody was higher than of those patients who received unlabeled antibody. Spot images indicated that radioactivity level in the liver, spleen and bone marrow decreased when unlabeled antibody was available. The use of unlabeled MoAb before the injection of labeled MoAb seems to enhance the amount of radioactive MoAb in the blood with a simultaneous decrease in the liver accumulation. A multinational gated cardiac blood pool intercomparison study has been performed in Europe under the auspices of the World Health Organisation. This study used mechanical moving plate transmission phantoms (the "Danbury Heart") designed to simulate left and right cardiac ventficular motion with a constant background activity. One hundred and fifteen Nuclear Medicine Centres in 11 countries took part in the study and provided 144 independent sets of data relating to the equipment and acquisition parameters, details of processing protocols, and measured ejection fraction (EF) for the phantom used. The distribution of results for the measured EF, as a percentage of the true value for the relevant phantom, was found to be bimodal. Inspection of the data showed that EF results from different makes of computer (20 manufacturers represented) fell into two distinct groups with means of 90.6% and 98.1% (p<0.001), This suggests that there are significant differences in EF algorithms leading to variations in results even where there is a constant background activity. Further differences are to be expected in the physiological situation with the variations in background subtraction methods. These results emphasize that a consensus should be reached for standardisation of software analysis protocols for cardiac investigations. Phantoms represent a standard way to control the quality of measurement in nuclear medicine. While physical and mathematical phantoms satisfy the needs of checking the quality of equipment, they may not be fully relevant to check the quality of a clinical software Recently, the software phantoms (clinically validated patient data available in a standard format) have been introduced for the purpose. They meet most of clinical quality control requirements except the need of precise quantification: values of derived diagnostic parameters are estimated in uncertain confidence limits. In order to overcome this drawback we suggest to complete the spectrum of testing tools by a hybrid phantom which combines some features of simulated and software phantoms. The hybrid phantom is made with the help of factor analysis: (I) the standard software phantom is decomposed to oblique factors and noise residuals, (2) factor curves are either modified or substituted by those generated by a physiological model, (3) hybrid dynamic data are reconstructed using original factor images and new factor curves, {4) hybrid phantom is completed by an addition of original noise. The hybrid phantom thus represent the sequence of images with real structures and S/N ratio close to original, manifesting the known dynamics generated by physiological model. For the purpose of semiquant±tative (comparative) evaluation and/or the separation of spatial and temporal information, factor curves of another patient may also be substituted after adjustment to original factor contributions. In order to test the effect of noise, a series of identical phantoms with different contributions of original noise can be generated The hybrid phantom is considered to be a useful supplement rather than a substitution of the simulated and software phantoms Phantoms generated using time-activity curves of different origin are demonstrated together with the source data. Applications in the quality control of various clinical software are demonstrated and discussed. A v a n Lingen, OS Hoekstra, JC Roos, G J J T e u l e Free U n i v e r s i t y Hosp, Amsterdam, N e t h e r l a n d s The A data base of clinical studies is necessary to establish normal values and range and typical values corresponding to diseases. It is also needed to assess variability between operators and centers, and is a mandatory tool for software quality assurance. To fulfil these goals, an European Nuclear Cardiology Data base (ENCD) is being built with the collaboration of the European Association of Nuclear Medicine, the European Society of Cardiology and the European Communities COST B2 program "Quality Assurance of N,clear Medicine Software". The ENCD includes normal subjects and patients with typical patterns of myocardial ischemia, recent myocardial infarction and cardiomyopathy, selected according to predefined criteria which exclude radionuclide data. Acquisition protocols have been designed for planar gated blood pool studies, planar and SPECT myocardial studies using TI-201 and Tc-99m Cardiotite (Eur J Nucl Med 1993, 20:59-65). Acquisition portfolios have been created and widely distributed for the collection of the necessary clinical and test data, respecting medical privacy. The portfolio keys have been defined in agreement of 41 European nuclear medicine physicians and cardiologists. To participate, one must provide radionuclide acquisition data, converted into Interfile format, with completed portfolios. These will be included in the ENCD after a group of experts have checked that the data meet the required quality. In order to prepare further steps, the acquisition portfolio includes the parameters to be obtained by processing. A processing portfolio, now being created, will be distributed with the ENCD. The numerical values will be processed with variance analysis, to help define ranges. It is planned that the ENCD will be made available on CD-ROM to the nuclear medicine community in 1995. The ENCD can then be applied by any user for all of the above goals. M.Gi~anti, A.Duatti*, L.Uccelli, C.Cittanti, P.ColamussiAnd A.Piffanelli. Tc-99m radiopharmaceuticals containing the Tc---N triple bond have been recently ina'oduced into the field of nuclear medicine after the advent of an improved synthesis of the TcN group at tracer level. These radiopharmaceuticals exhibit high in vilro and in vivo stability and can be easily functionalized to obtain radiopharmaceuticals having diverse biological properties. In particular, the incorporation of a suitable ligand into the structure of these complexes may lead to the preparation of a tracer for monitoring metabolic pathways. Glucose is a fundamental substrate for heart and brain metabolism and the stable incorporation of a glucose derivative into the chemical structure of a Tc-99m complex should be a fundamental step in the effort to obtain a Tc-99m-analogue of FDG. In this paper, we describe the preparation of Tc-nitrido compounds containing two different glucose derivative and their biodiswibutions in rats. The complexes were prepared by reaction of a prereduced TcN-intermediate with 1-thio-B-D-glucose and D-glucaminedithiocarbazate, respectively. The yields of formation were always higher than 95%. The compounds were stable in vitro for a period of 4 hours.They have been characterized by TLC chromatography and by comparision with the corresponding Tc-99 analogues. Both complexes have a square-pyramidal structure with an apical TcN group. In complex 1, two 1-thio-l]-D-glucose ligands were found to be coordinated to the metal center through the negative thiol sulphur atom and one negative hydroxilic oxygen atom, giving a final dianionic compound. In complex 2, the comdination of two monoanionic dithiocarbamate ligands through the four sulphur atoms led to the formation of a neutral compound. Biodistributions in rats showed that complex 1 is rapidly eliminated throgh the kidneys as a results of its negative charge. On the contary, complex 2 showed both urinary excretion and a significant heart uptake (1.6% i,d.). CoCI 2 has been reported to stabilise Tc-99m d,I-HMPAO (PAO) prepared from a Ceretec kit with 1110 MBq (30 mCi) ToO 4" (RCP at 5h = 81-91%; EJNM 1993; 20: 661). In our experience, addition of 200 ~tg COC12.6H20 is even efficient in stabilising multi-dose, high activity (150 mCi Tc-99m) Ceretec preparations with RCP >_ 85% at 6h. When used at 5h, such preparation yielded brain images in a baboon, and human WBC labelling yields comparable to those obtained with a fresh 30-mCi PAO preparation. However, up to now no evidence is available on the clinical usefulness and safety of PAO stabilised in this way. Moreover, the formation of a yellow colour on addition ofCoCl 2 suggests a Co-HMPAO complexation reaction. Using Co-57 we have performed biodistfibution studies in mice on three preparations, i.e. (a) 57COC12; (b) 57COC12 + 0.5 nag d,l-HMPAO; (c) 57COC12 + 0.2 mg COC12.6H20 + Ceretec kit (0.5 mg d,l-HMPAO + 7 ~tg SnCI2.2H20), and also compared their behaviour on paper chromatography. The results show that in (b) and (c) a lipophilic Co-HMPAO complex is formed with a favourable biological profile, which significantly differs from that of CoCl 2. Its plasma clearance is higher (14% of I.D. in blood at 2rain and 3.8% at 10rain, vs. 16.5% and 13.5% respectively for CoC12) , and it is excreted by both the renal and hepatobiliary system. The excretion of CoCl 2 is slower and almost exclusively by the renal system. Co-57 d,I-HMPAO exhibits negligible brain uptake (<0.25% of I.D. at t = 2, 10 or 30min vs. ~ 1% for Tc-99m d,I-HMPAO), despite its lipophilie nature. The results justify a next-phase study with multi-dose Co2+-stabilised PAO preparations, especially with regard to pharmacological safety. A. Afsan, M. Jehangir, M. Ashraf, E. Chiotellis Nuclear Medicine Oncology, Radiotherapy Inst., PINSTECH, Islamabad Pakistan, PUN~AP Univ. Lahore Pakistan and N.C.S.R. "Demokritos" Athens, Greece Ethyl cysteinate dimer ECD, labelled with technetium-9gm has been proposed recently as a promising radiopharmaceu-~jcal for brain perfusion imagina. However preparation of ~mTc-ECD reported to proceed'vil a two step kit ~ormulation requiring reconstitution with saline and pH adjustement prior labelling. In the present work we describe a sinale composition instant freeze dried kit for the preparation of 99mTc-ECD complex. Various stabilizers such as EDTA, mannitol etc., as well as pH and SnCl 2 concentrations were tested in order to evaluate the optimal ingredients. Optimum formulation contained ECD.HCI I mg, 0.5 mg EDTA, stannous chloride and mannitol as stabilizer. Formulation was performed under controlled temperature and nitrogematm, at pH 6.0. The lyophilized kit was recontrituted with 2 ml of pertechnetate eluent, resulting in 97.5% yield in 99m-ECD complex. A radiochemical method of analysis has been also developed permiting the identiZication of active complex and impurities. Thus by electrophoressis in Wha~an No I (250 V), mobile phase phosphate buffer pH 6.8, ~mTc-ECD migrated towards anode at 2.6 cm, while pertechnetate at 10.5 cm. Further the instant freeze dried kit formulation developed was evaluated in primates, monkeys and human. Data demonstrated that activity in the brain tissue was retained until approx. 90 min p . i . , resulting in high qual.ity images of brain. Thus the new formulation can be proposed as a reliable kit for the routine preparation of 99mTc-ECD complex. 1231-interleukin-2 (IL2), is currently used for the in vivo detection of lymphocytic infiltration in man. The ready availability and low cost of 99rnTc suggest the use of this isotope for the labelling of IL2. We have previously described a method for labelling biologically active peptides with 99mTc (EurJ Nucl Med. 1992. 19(8):625) . The aim of this study was to test different purification methods and to study the biodistribution of 99Tc-IL2 in mice. Human recombinant 1L2 was labelled using a bifunctional N3S chelating agent as previously described. Labelled IL2 was purified by gel filtration (G50M, PD10 column, Pharmacia), and reversed phase (RP), chromatography using a C18 Classic Sep-Pak column (Waters) (0.1% H3PO4, 5% ethanol, pH=2 solvent A; 0.5% H3PO4 in ethanol, pH=3, solvent B), or a C8 HPLC column (Beckman) (0.1% trifluoro acetic acid (TFA), 5% acetonitrile, pH=1.7 solvent A; 0.1% TFA in acetonitrile, pH=2.2, solvent B). The receptor binding capacity of 99mTc-lL2 was tested by an indirect assay. Biodistribution of 99mTc-IL2 (< l,ug), purified by either method was studied in Balb/c mice (n=8). Sep-Pak purified 99mTe-IL2 (M5,ug), was also tested in normal volunteers in man (n=2). IL2 LE was -20% (SA: ~3GBq/mg). 99mTc-IL2 purified by gel filtration, when injected into mice was taken-up mainly by liver, suggesting aggregation of IL2 during labelling. 99mTc-IL2 eluted at --60%B in the RP HPLC, 100%B was used for elution of 99mTc-IL2 in a small volume with Sep-Pak. Studies of receptor binding indicated that 99mTc-lL2 retained unaffected its receptor binding capacity. Biodistribution of RP purified 99mTc-lL2 showed a kinetics similar to that of iodine labelled IL2. 99mTc-lL2 metabolization, determined by TCA precipitation of sera, showed a higher in vivo stability compared to iodine labelled IL2, probably due to the fast in vivo dehalogenation of tyrosine residues of iodine labelled IL2. Studies in normal volunteers showed that 99mTc-lL2 has a kinetis similar to that of 123I-IL2. Our results suggest the use 99mTc-lL2 in man for the in vivo detection of lymphocytic infiltration. The specific binding and technetium chelating strength of proteins can be increased by the covalent attachment of a bifunctional chelating agent (BCA) that forms stable complexes with technetium. We have now synthesized N-hydroxysuccinimidyl 3,4-di-(S-benzoylmercapto)butyryl S-benzoylcysteinate, a trimercaptomonoamide BCA, and coupled it to human serum albumin (lISA). This was of particular interest because a stable and easy-to-prepare 99mTc-HSA derivative would be useful as a blood pool agent in radionuclide ventriculography. After coupling of the BCA to albumin in molar ratios of 8/1, 16/1 or 25/1, the S-benzoyl groups were removed by incubation with a hydroxylamine solution. Direct labelling could be performed by addition of 10 gg Sn 2÷ followed by 1 ml of a 99roTe-generator eluate. The preparations were analysed and purified using FPLC on a Superdex 200 HR 10/30 column eluted with a 0.05M phosphate buffer pH 7.5 containing 0.15M NaCI and 1 mM NaN 3. The biological behaviour and especially the retention in the blood of this new preparation was evaluated in mice and a rabbit. Blood retention was clearly higher than that of unmodified 99mTc-HSA and was comparable to that of the reference compound a2SI-HSA. Finally, a preliminary study in a human volunteer was performed with the 16/1 preparation. At 2 hours p.i., 83% of the initial activity was retained in the vascular compartment and only 1.2% was excreted into the urine vs, respectively 59% and 17% for unmodified 99~Tc-HSA. These results indicate that the preparation of a stable 99mTc-HSA derivative is possible using the bifunctional chelate approach, resulting in a preparation with a clearly higher vascular retention. T1201/Tc99m subtraction (T1-Tc) scintigraphy is a well established method in the detection of parathyroid adenomas. Recently Tc99m-Sestamibi (MIB1) has been proven to be rapidly cleared from the thyroid tissue and longer retained in the parathyroid adenomas c l e a r l y delineated in a late image. 9 patients (8F, 1M; aged 57-79 yrs) with c l i n i c a l and biochemical pattern of primary hyperparathyroidism (Ca:10-23 mg%; P:2.7-3.8 mg%; Intact PTH: 127-1450 pg/ml) were studied with both methods. All of them had surgical confirmation of parathyroid adenoma. All patients were injected with 20 mCi of MIBI and imaged at 30 min and again at 2--3 hrs; one week l a t e r the T1-Tc scintigraphy was performed. MIBI scintigraphy correctly revealed s o l i t a r y adenoma in the neck in 8 patients and a mediastinal adenoma in one, c l e a r l y localized by SPET. T1-Tc scintigraphy revealed the adenoma in 7 patients, including the mediastinal adenoma. MIBI scintigraphies were of better quality than those obtained with T1-Tc due to the physical properties of Tc99m and not requiring any subtraction techniques. Unfortunately we found the parathyroid pattern of MIBI in 3 patients with Hurtle c e l l carcinoma of the thyroid, so l i m i t i n g the s p e c i f i c i t y of the method. However the dual-phase technique with M1BI promises to be superior to the dual-isotopes technique in the scintigraphic evaluation of parathyroid adenomas. In case of multifocal functional autonomy (MFA) or of toxic adenoma (TA), hyperthyroidism (blocked TRH-test) takes place above a threshold volume of autonomous (A) cells. 1311 therapy is successful, because for an identical specific cellular density, A thyroid (th) areas withhold more radioiodine than functionally suppressed areas. In independence of the functional status, 99mTc-MIBI (Dupont) is a marker of cellularity. As well in A (AR) as in suppressed (RR) th regions, a dissociation between regional function (rF) and regional cellularity (rC) can be depicted by double tracer scintigraphy, rF and rC are then scanned sequentially with 131 (123)1 (7 MBq) and 99mTc-Hexamibi (Z00 MBq). After background subtraction and normalization, the weighted rC image is subtracted from the weighted rF image. In the resulting subtraction image [F-C], the ratio of count rates: (A area/the most suppressed area) results in the "toxicity" index T. AR[F-C] AR = counts in A regions T . . . . . . RR = counts in reference region ("normal" function) I~esults: Average/1SD of "T" (n=77), of TT4 (nmol/I), of TT3 (nmol/I) and of TSH (mU/I) in 5Z hyperthyroid patients (MFA: n=36, TA: n=l 6) before and after 1311 therapy (150 Gy/th or 30 Gy/A areas). 2_+1.8 Within a follow-up time of 9-ZZ months did none of these "T" residues induce recurrent hyperthyroidism. This new quantitative method is an alternative to the T3-suppression and/or to the TSHstimulation tests, to delineate functionally A th parenchyma. pg/g creatinine level (1920) to a level above 100 IJg/g creatinine (WHO standard), during the years 1981-1990. Our study in 199Z in 55 healthy probands and Z34 patients, thyroidectomized because of differentiated thyroid carcinoma, showed still and again an unexpected iodine deficiency: 87+_36 IJg/g creatinine. Only Z4% of the healthy volunteers fulfilled the WHO criteria. In a single healthy volunteer evaluated 9 times repeatedly, the average urinary excretion of iodine was 70 pg/g creatinine, the WHO standard was reached only in 11% of cases. Euthyroid patients on T4 supplementation (0.15+0.04 mg T4/day or 98+-3 pg iodine/day) had WHO-insufficient iodine excretion levels only in 19%: hormonal substitution is thus a provider of a sufficient iodine supply in Berne. Thus, iodine supply via iodinated kitchen salt only is not as stable as had been hoped for. The reasons are multiple: a reduced intake of table salt, increased consumption of imported food, which have not been prepared with iodinated salt, diversified eating habits, increased number of meals taken outside the family table due to a rising female professional occupation, longer transport times to the working place and increasing numbers of single's households. It is to be expected, that a deficient iodine supply will remain a reality in an affluent, goiter endemic society as long as iodinated kitchen salt will not be used generally, for instance in the whole European Community. Chr.Reiners, A.Yavuz, T.Ugur, G.Caspari, W.Sonnenschein, Th.Olbricht Clinic for Nuclear Medicine and Internal Medicine, University of Essen The quantification of stable iodine content of the thyroid (STIC) is of great importance for the evaluation of new therapeutic strategies in the treatment of endemic goiter. We therefore developed a stationary system for X-ray fluorescence analysis (XFA) of STIC. This system consisting of a collimated Am-241 source (activity 11.1 GBq), a HPGe semiconductor detector and a spectrum analyzer has a sensitivity as low as 0.1 mg iodine per ml of thyroid volume. The coefficient of variation for duplicate measurements amounts to 10% for a STIC of 0.1 mg/ml, to 7% for 0.3 mg/ml and 5% for 0.5 mg/ml respectively. In normal controls (n=165) STIC averages to 0.32 + 0.14 mg/ml (mean + SD). In patients with endemic goiter, S-TIC is significantly lower (diffuse goiter: 0.25 + 0.21; P < 0.01; nodular goiter: 0.26 + 0.15; P< 0.01). A group of 28 patients with moderate endemic goiters has been treated with 200 ug of iodine per day for a time period of 9.1 _+ 4.5 weeks. Mean thyroid volume decreased significantly from 26.1 +__ 13.4 ml to 19.8 + 9.5 ml (P< 0.001). STIC increased with high significance from 0.19 + 0.11 mg/ml to 0.35 + 0.14 mg/ml (P < 0.0001). The study shows that a short treatment period with 200 ug of iodine daily may result in a significant decrease of goiter volume, which is correlated with a highly significant increase of STIC. XFA -a genuine nuclear medicine procedure -should be employed on a broader scale in epidemiological or therapeutic studies in thyroidology. H o s p i t a l , Z g i e r z , P o l a n d Tc-99m Sestamibi (MIBI) has been proposed for the visualization of supressed thyroid tissue in patients with autonomously functioning thyroid nodules (AFTN). However, the effect of TSH on thyroid uptake of MIBI is contraversial. The aim of this study is to evaluate the effect of TSH and metabolic activity of AFTN on thyroid uptake of MIBI in patients with toxic and non-toxic solitary AFTN. Sixteen patients (13F, 3M) with toxic and 12 patients with nontoxic (9F, 3M) solitary AFTN visualized on Tc-99m pertechnetate scan were included in the study. MIBI scans were performed 15 and 90 min. after IV injection of 350-400 MBq of the agent. The scintigrams were analysed both visually and semiquantitatively. For semiquantitative analysis ROIs were drawn over AFTN and contralateral normal lobe and the mean counts in every ROIs were found. After background correction, by dividing nodular counts to extranodular tissue counts nodule / extranodular tissue ratios were calculated. The results are shown on the The results demonstrate that the uptake of MIBI in toxic AFTN is significantly higher than that of non-toxic AFTN. MIBI scintigraphy also shows good visualization of extranodular tissue in fion-toxic AFTN compared to toxic AFTN. In conclusion, both metabolic activity of AFTN and TSH might be effective on the thyroid uptake of MIBI. z S t r a h l e n k l i n i k UKRV Free U n i v e r s i t y of Berlin, G e r m a n y By use of c o m p a r t m e n t a l analysis a rapid initial thyroidal u p t a k e of p e r t e c h n e t a t e in the normal and d i s e a s e d g l a n d has been described. After withdrawal of hormone substitution in thyroidectomized patients, TSH increase and iodine depletion are parallel phenomena. An endo-and/or exogenously rising TSH level is often considered as a prerequisite for an efficient radioiodine therapy in case of differentiated thyroid carcinoma. Moreover, supply of "cold" iodine should be maximally reduced, in order to increase the uptake of 1311. Some experimental data were to confirm the hypothesis, that the correlation between TSH increase and iodine depletion is only mimicked. Cold iodine in plasma (mainly T4) was measured in 55 healthy volunteers (A, B) and in 3 patient groups with differentiated thyroid carcinoma after thyroidectomy: hypothyroid patients with (C, n=30) and without (D, n=67) thyroid remnants and euthyroid patients under T4 substitution (£, n=137). Results: The ratio of 131 I/cold iodine was 3 times higher in group E than in group D patients. Euthyroid patients under T4 (0.15+0.04 mg T4/day or 98_+3 pg iodine/day) (E) had plasma iodine values by 40% higher than hypothyroid patients (D). An increasing TSH level was associated with a decreasing plasma iodine level: by 40% after thyroidectomy (C), by 51% after an additional radioiodine "elimination" of thyroid remnants (D). On the opposite, decreasing TSH was associated with increasing plasma iodine. This -only initally -linear correlation ("n=0.64") is but an illusion. The effective stimulation of an increased 1311 uptake is due to the depletion of competing cold iodine after withdrawal of the substitutive T4: this manoeuvre increases the specific activity of radioiodine. The parallel increase of TSH in itself is not the reason for a better radioiodine uptake in the tumor. Treatment of hyperthyroidism with 1-131 is well accepted and usually results in a substantial decrease in thyroid volume. However, few data are available on the effect of 1-131 treatment on thyroid volume reduction in non-toxic goiter and the results are seldom evaluated by objective methods. CT is an accurate and reproducible method to determine volume reduction. The aim of this study was to investigate the effect of 1-131 on goiter volume measured by CT. Twenty-seven patients (mean age: 58.1 -+ 10.5 yr) with complaints of goiter entered the study. All patients had a normal plasma TSH, or a suppressed plasma TSH with a normal plasma T4 (or T3). The administered dose was intended to be 3.7 MBq 1-131 per cc thyroid volume, corrected to a 100% uptake at 24 hours. For the purpose of dose calculation, volume was estimated from a planar Tc-99m pertechnetate scintigraphy. Patients received a dose between 500 and 3700 MBq. Prier to therapy, all patients underwent a CT of the neck, performed with contiguous 5 mm sections, and without using intravenous contrast material. Volume measurements were made using the summation-of-areas technique. CT was repeated one year after therapy. The thyroid volume prior to therapy measured by CT was 203.1 -+ 144.5 cc. One year later the volume was 145.8 -+ 115.7 cc. Volume reduction was obtained in all patients (mean: 32.8 + 17.5%). Differences in size, plasma TSH level, radioiodine uptake, and prior thyroid medication did not change the outcome. All but three patients (11.1%) were satisfied with the result. These three patients showed a reduction of 25.2 _+ 10.0%. Hypothyroidism occurred in four patients (14.8%), in whom volume reduction was 43.2 -+ 16.2%. No other side effects occurred. In conclusion, 1-131 therapy for volume reduction in non-toxic goiter is a safe and effective treatment, but the degree of goiter reduction cannot be predicted by pre-treatment thyroid volume, TSH levels, diagnostic radioiodine uptake or thyroid medication. E. Derebel% A. Koyuncu, S. Erdem, M. 0nl~, Y, Yt3zer, H. Ozkdlg Depts. of Nuclear Medicine, Surgery, Ege University, izmir, Turkey TI -201 has been used in order to differentiate malign and benign thyroid nodules for a long time. Quite different results were reported. Increased uptake of TI-201 in malign tumor are beliaved related to vascularity of the tumor, basicaly. We aimed to investigate the role of early and delayed TI -201 in differentiation of malign and benign thyroid nodules, comparing with Tc99m-pertechnetate perfusion images. 28 patients with solid-solitary-hypoactive thyroid nodules were included in the study. 15 minutes and 3 hours after injection of 2 mCi TI-201, static images of 400-500 Kcounts are obtained, using LEGP collimator. Thereafter, 2 mCi Tc 99m-pertechnetate were injected intravenously. Soon after the injection first minute perfusion images were obtained. Nodule Activity Index (NAI) was calculated from each static image. Results were evaluated semiquantitatively. NAI greater than 100 were accepted as the criteria of malignancy. 1311 therapy is a widely accepted treatment for large, toxic multinodular goiters. There is, however, a reluctance to use 1311 for reducing the volume of large euthyroid goiters for fear of too high absorbed doses in these patients. We compared absorbed doses in thyroid, neighbouring tissues and rest of the body in eu-and hyperthyroid patients with large, nodular goiter (>100 g). The administered activity of 1311 (AA) was calculated to retain 3.7 MBq/g thyroid tissue at 24 hours. Thyroid weight (TW) was estimated from a rectilinear scan. In 11 eu-and 9 hyperthyroid patients, thermoluminescence dosimeter (TLD) measurements were performed for 5 to 15 days after t311 therapy on 3 locations: on the skin overlying thyroid, submandibular and parotid gland. Extrabolation of monoexponential fits from day 2 onward was used to determine the cumulated absorbed doses on the skin. Furthermore, in 5 eu-and 6 hyperthyroid patients thyroid uptake (lead shielded Nal cristal) and whole-body retention (whole-body counter) were measured daily for 7 to 15 days, Residence times in thyroid and rest of the body (integration of activities over time using extrapolation of monoexponential fits from day 2 onward) were entered into the MIRDOSE2 program to calculate absorbed doses. TLD measurements: TW, 24h 1311 uptake (RAIU) and AA were 214+60 g, 33 +9% and 2.5+0.8 GBq, rasp., for eu-and 215_+69 g, 50+15% and 1.8+0.9 GBq for hyperthyroid patients. Absorbed doses on the skin were 4.1+1.1 Gy (thyr), 1.0!-_0.4 Gy (subm) and 0.3+0.1 Gy (parot) for eu-and 4.0+-1.5 Gy, 1.2+ 0.5 Gy and 0.4-+0.2 Gy for hyperthyroid patients (diff. eu-/hyperthyroid n.s.). Thyroid uptake and whole-body retention measurements: TW, RAIU and AA were 217+85 g, 36d:12% and 2.4-+1.1 GBq for eu-and 219-+75 g, 49!-_5% and 1,8_+0,8 GBq for hyperthyroid patients. Absorbed doses in the thyroid were 82-+19 Gy for eu-and 76-+19 Gy for hyperthyroid patients (n.s.). Total body absorbed doses were 0.7+_0.3 Gy for both groups and absorbed doses in other target organs were also comparable for eu-and hyperthyroid patients. In conclusion, absorbed doses in thyroid, neighbouring tissues and total body did not differ significantly between eu-and hyperthyroid patients with a lap ~ e, muitinedular goiter treated with 1311. In view of the wide acceptance of 311 therapy for large, hyperthyroid goiters, radiation burden is no reason to discourage 1311 therapy for volume reduction of large, euthyroid goiters in elderly people who refuse surgery or in whom surgery is contraindicated, L.Dominguez-Gadea, L.Diez, G.Piedrola*,C. G,Rubini, S.Iliceto*, F.Lauriero, D.Rubini, L.Galiuto*, P .Rizzon*, A.D 'Addabbo. The complete assessment of acute myocardial infarction (AMI) requires the evaluation of regional function and myocardial perfusion. Two dimensional echocardiography (2DE) evaluates myocardial dysfunctions, and during infusion of Low Dose Dobutamlne (LDD) recognises hypoakinetic Myocardial Segments (MS) with contractile reserve. Myocardial contrast echocardiography (MCE) with intracoronary injection of a sonicated contrast medium gives information about myocardial microvascular integrity. From intracellular uptake of 99mTc-MIBI it is possible to obtain the regional perfusion patterns. To evaluate if there is a 99mTc MIBI uptake in postinfarction dysfunctioning MS with contractile reserve and microvascular integrity, we studied 5 pts with AMI (3 anterior, 1 lateral and 1 posterior) . All pts underwent 2DE monitoring (at day 1,3,5,7,15), LDD (5 mcg/kg/min for 5 rain. and i0 mcg/kg/min for a further i0 rain.) at day 5, MCE at the time of coronary angiography, with selective intracoronary injection of sonicated Ioxaglate, and 99n~c-MIBI SPET. 13-(p-[~231]iodophenyl)-3-(p-phenylene) tridecanoic acid (PHIPA) is a radiolabelled synthetic long chain fatty acid with prolonged myocardial retention (biological half life up to 70 hours) due to a trapping mechanism caused by the p-phenylene group in the alkyl chain. The present study examined the ability of myocardial scintigraphy with PHIPA in comparison to thallium-201 for the detection and estimation of coronary artery disease. In 8 patients with chronic coronary artery disease and stable angina pectoris, 1800 SPECT images were acquired 30 min after injection of 160 MBq PHIPA at stress. Two to three days later, separate rest studies were performed (identical imaging protocol). The regional activity in each of 32 myocardial segments per patient was compared to that of stress/redistribution thallium-201 images obtained within 1 week after the PHIPA studies. The PHIPA stress images showed 16.6 + 6.1 abnormal segments per patient (thallium-201 stress: 17.0 -+ 5.1 segments), and the PHIPA rest images showed 16.8+6.8 abnormal segments (thallium-201 rest: 13.2+8.2 segments). Of 134 abnormal segments with PHIPA during stress, only 9 (6.7%) showed reversibility on rest images as compared to 37 out of 142 segments (26.0%) on thallium-201 redistribution images (p < 0.001 ). The virtually identical number of abnormal myocardial segments obtained with stress thallium-201 and test PHIPA scintigraphy suggests rest PHIPA imaging as a promising tool for the identification of poststenotic myocardium. With respect to the evaluation of myocardial viability, however, an optimal imaging protocol remains to be established. Here we report the results of a one year follow-up. The patient series consists of 12 men, aged less than 65 years who had survived their first MI. Ten of the patients were succeeded to re-study after one year follow-up using these 3 tracers. There were no significant changes between these two examinations in the size of the MIBI-defect (9.4 ± 2.5 vs 10.4 ± 3.0 %, mean ± SEM), MIBGdefect (17.0 ± 2.8 vs 17.1 ± 2.5 %) and pPPAdefect (9.4 ± 3.0 vs 8.4 ± 2.5 %, respectively). However, the metabolic reserve was significantly (p < 0.05) improved (11.6 ± 4 . 1 % ) and the size of viable but denervated myocardium was slightly increased (5.7 ± 9.5 %; p > 0.05). The results suggest that there are no significant changes in the infarct size, in the extent of perfusion defect and no re-innervation of the sympathetic nerve endings in the infarcted region during the one year follow-up. The metabolic reserve in the peri-infarcted region was the only parameter that improved during the follow-up. Rest-SPECT with MIHA frequently shows an increased level of uptake in areas with irreversible exercise SPECT-TI201 defects. Such a miss-match pattern between a flow (TI201) and a metabolic (MIHA) tracer might correspond to ischemic but v i a b l e myocardium, but the r e l a t i o n s h i p with quantified level of TI201 uptake remained to be clarified. Exercise SPECT-TI201 with rest reinjection and rest-SPECT with MIHA were performed in 83 pts with myocardial infarction. Exercise extent of E x -I U d e t e r m i n e d on MIHA was related to the quantified extent of areas w i t h a TI201 u p t a k e ~ 50% of normal (p<.001), but the correlation was weak (R =.5) ; areas with ~ 50% of TI201 uptake were larger than those with Ex-IU on MIHA in 86% of pts. M I H A r e s t -S P E C T frequently shows an increased level of u p t a k e in areas w i t h i r r e v e r s i b l e defects at T l 2 0 1 -r e i n j e c t i o n . Such areas are likely to have a ~ 50% of TI201 uptake, but are not accurately identified by SPECT-TI201 data. Serial rest-SPECT with Sestamibi was used to assess the effects of the administration of a beta-blocking agent (bisoprolol) at the acute phase of MI. Eighteen pts with <8 hrs acute MI treated with thrombolysis, were randomly assigned to treatment with bisoprolol or placebo. Sestamibi was injected at the time of thrombolysis and before the IV administration of the study agent, and an initial SPECT acquisition was started 1 to 2 hours later. Treatment was continued orally during a 4-week period in all but 3 pts (i death (bisoprolol) and 2 heart failure (placebo)). A 4-week evaluation was performed using radionuclide angiography, and rest and execise SPECT w i t h Sestamibi. No difference was observed, between pts with (n=8) and those without (n=7) bisoprolol treatment, on extents of initial rest SPECT defects and on all data obtained at 4-week (radionuclide LVEF, extents o f : e x e r c i s e and rest SPECT defects). However, the decrease of defects size, between initial and 4-week rest-SPECT, was greater in pts treated by bisoprolol than in placebo pts (% LV-area: -14±8% vs -6!4%, p<.02). At the acute phase of thrombolyzed MI, betablocking therapy (bisoprolol) enhances extent of salvaged myocardium. This is evidenced on serial Sestamibi rest-SPECT, which appears to be a very sensitive technique to detect beneficial effects of treatments proposed in thrombolyzed MI. D.Moka, P.Theissen, U.Sechtem*, H.Schicha. Klinik und Poliklinik ftir Nuklearmedizin, *Klinik III ftir Innere Medizin, University of Cologne, Germany. To assess myocardial viability after nontransmural anterior myocardial infarction (MI), 19 patients with critical LAD-stenosis (>80%) and anterior wall hypokiuesia (A) and 10 healthy volunteers were examined on a Philips 1.5 Tesla imaging/spectroscopy MR system using a surface coil and Gyroscan/ISIS software. All patients had minimum diastolic wall thickness of 6 mm as assessed by gradient-echo magnetic resonance imaging. Patient spectra were recorded under optimal antiischemic medication. The cube-shaped volume of interest was placed into the apical-septal area of the myocardium. Spectra were corrected for Tl-effects and blood contamination. To eleminate the possibility that alterations of the spectra were mainly caused by LAD-stenosis, 4 additional patients (B) with critical LADstenosis but normal left ventricular (LV) function were examined following the same protocol. The effect of glyceroltrinitrate (GTN) was evaluated in 4 further patients (C), who had the same clinical features as the 19 patients mentioned above. MRS was performed without antiischemic medication (washout period >one day) and during intravenous application of GTN. Mean PCr/ATP-ratio (A) was reduced from 1.74 + 0.23 to 1.24 + 0.18 (p = 0.01 unpaired t-test) as compared to normai controls. Patients with normal LV function (B) had PCr/ATP-ratios similar to those of normal controls (p = 0.23). After GTN infusion (C) PCr/ATP-ratio rose from 1.12 + 0.08 to 1.32 + 0.13 (p = 0.04 paired t-test). The alterations in myocardial metabolism at rest are likely caused by the wall hypokinesia, because patients with critical LAD-stenosis without anterior wall hypokinesia showed a normal PCr/ATP-ratio. A possible reason could be a degeneration of the myocyte s ~/fter MI. An other possibility is a chron!c cellular ischemia produced by a distuibed microperfusion after MI. This theory is supported by an improvement of the energy metabolism in hypokinetic regions by GTN. To differ whether a reduction of the PCr/ATP-ratio is really a sign of cellular ischemia in coronary heart disease further investigations are needed. The results of dobutamine (DOB) stress scintigraphy and 2D echocardiography were compared in 21 patients (mean age 58 years) with old MI. 9 patients had an inferior, 8 an anteroseptal, 2 an apical and 2 an anteroseptal and inferior resting WMA documented by echocardiography. :DOB stress was performed by using a stepwise increasing dosage (5-10-20-30-40-40 micrograms/kg/min, each step over 3 min). During the test, continuous echocardiographic monitoring was performed. If the age-dependent submaximal heart rate was not attained after the second 40 micrograms/kg/min dose, 0.25 mg/min of atropine was given over 4 rain. 200 MBq of SESTAMIBI was injected immediately after termination of the DOB or atropine infusion. Myocardial perfusion SPECT studies were performed according to a one-day protocol (750 MBq SESTAMIBI for the resting study). Echocardiography was evaluated from the standard views. SPECT studies were evaluated by a combined consideration of the short-axis, horizontal and vertical long-axis slices and quantitative polar maps. Improved wall motion (WM) at low dose DOB (viability) was signalized in 6 myocardial regions in 5 patients. In these territories scintigraphy documented stress-induced ischemia in 3 cases, an enhanced defect size at rest in 1 patient, and a persistent perfusion defect in 2 cases. Stress-induced WMA was documented in 8 patients. These ischemic segments were concordantly identified with scintigraphy in 6 patients; myocardial perfusion was normal in 2 patients. On the other hand, scintigraphy documented stress-induced myocardial ischemia in 10 regions of 8 patients, without changes in regional WM during stress. 5 of these regions had resting WMA, but 5 did not. It is concluded that the results of DOB stress myocardial SPECT and 2D echocardiography are different in nearly half of the patients with old MI, and these diagnostic modalities can not replace each other. SPECT in identifln~ myooaxdial viability. We studied 17 patients ( 15 m, 2F, mean age 53+/-gyrs ) with multivessel coronary artery disease ( CAD ), previous infarction and reduoed ejection ( EF ) at resting echocardiography ( < 30% ). We used a sixt~n scgmants ventdoular model for DSE and TI SPECT. DSE was analysed using a score index ranging from 1 (nonnokinesis) to 4 (dyskinesis). Each short axis reconstraoted from SPECT raw images was divided into six segments and the mean count was caloulated for each one. Sogment~fl 29 uptake was determina~ed as a percentage of the maximum among all short axis sections. A segment was considered viable when resting dyssynergy ( score > 2 ) showed an improvement of one grade or more during Dobutamine infusion and when 11 uptake was >50%. The findings of DSE and rest TI imaging were compared in a total of 272 segments, 232 of which wcrc dyssynorgyc segments: 150 were akinetio and 82 hypokinetie segments. Rest TI imaging showed viable myocardinm in 93/150 (62%) akinetie segments. Of them 76 (82%) showed no improvement at DSE. Of 82 hypokinetic segments 75 (91%) were seen as viable by TI imaging. Of them 43 (57%) showed no improvement at DSE. Thus, concordance between TI SPECT and DSE in idenfifing viable myocardium was dew: DSE showed wall motion improvement in 49/168 (29%) viable segments. Concordance was higher for non viable scgmems: 58/64 (91%). In conclusion, in patients with CAD and reduced EF, DSE if compared with TI SPECT as reference test, showed low sensitivity (29%), high specificity (91%) and moderate accuracy (46%) in detecting viable myocardium. Introduction: The accurate assessment of myocardial viability is of major importance in patients(pts) following myocardial infarction. Purpose: The aim of our study was to determine whether immediate thallium-2Gl(TI) reinjection(Ri) imaging provides adequate information regarding myocardial viability. In 23 pts with documented anterior wall infarction results of the immediate Ei procedure were compared with 1)TI rest(Re) redistribution(Rd) images, and 2)left ventricular wall motion(Win) obtained with radionuclide angiography(RNA). Methods: For the Ri procedure TI (75 MBq) was injected at maximal Ex and reinjected (37 MBq) immediately post Ex imaging followed by imaging 60 rain later. Re imaging was performed on a separate day 60 minutes after injection of TI (75 MBq). In 13/23 pts additional Rd images were acquired 3 h after Re imaging On each set of TI images, 8 segments(sugm) were visually and quantitatively analyzed. Ex data were compared with Ri images, Re images and Rd images. Myocardial segments were classified as viablelV÷ (normal, ischemic, non ischemic viable)}, and non-viable(V-). Left ventricu]ar Wm of the infarct region was studied by RNA performed at rest and during Ex Regional Wm was classified as normal, hypokinetic or a/dyskinetic. All but persistent a/dyskJnetJc regions were considered viable. Results: Ex-RB (n=184 segrn) £x-Rd (n=104 see'n) Wm(n=23 pts) V+ V-V+ V-V+ This prospective study was performed to predict the efficacy of coronary artery bypass grafting (CABS) in patients (pts) with severe left ventricular dysfunction (SLVD) in terms of increasing global ejection fraction (GEF) 3 months after CABS. The study protocol undertaken within a week before CABS included: I) simultaneous assessment of function iF) and perfusion (P) at rest using Tc-MIBI. The left ventricle was divided into 5 regions (apex, septum, anterior, inferior and posterolateral) and the same scoring system (O-normal to 3-severe) was employed for F and P. The difference (D) between the F-P scores was calculated in each patient; 2) low-dose Dobutamine (Dob) administration 5-10~gr/kg/min; 3) Isosorbide din±irate (Iso) given sublingually 5mgx3 at 5 min intervals (end point related to side effects). MUGA study was performed before and during Dob and Iso administration to calculate D GEF. Eighteen pts with GEF ~30% have so far been studied. These were divided into 2 groups (Gr) according to D GEF before and 3 months after CABG: (Grl -D GEF <3%; Gr2 -D GEF ~3%). The mean results of the pre-CABS studies were compared in the 2 Grs: D GEF/CABG D F-P Score D GEF/Dob D SEF/Iso Gr. Institute of Radiology, U n i v e r s i t y of Siena, Italy; * S t a e d t . K r a n k e n h a u s , P a s s a u , a n d #Klinikum Grosshadern, U n i v e r s i t y of Munich, G e r m a n y M o n t e p a g a n l and A. Coli. Depts. of N u c l e a r M e d i c i n e and #Cardiology, La Spezia and *Dept. of Medicine, Sarzana, Italy. The aim of this study was to analyze the effects of r a n d o m i z e d (factorial d e s i g n 2 X 2) n i t r o g l i c e r i n (N) and lisinopril (L) t r e a t m e n t In Dept. of Cardiology and PET Center, Univ. Hosp. Groningen, Netherlands. To investigate the potential role of ischemia in ventricular fibrillation (VF) late after myocardial infarction, we compared 6 pts with documented VF late after myocardial infarction (LaVF) and 27 healthy volunteers (HV). All pts and HV underwent quantitative dynamic positron emission tomography (PET) with N-13-ammonla for determination of myocardial perfuslon. Patterns of perfusion were assessed in 480 segments. The coefficient of variation (CV) as a measure of ischemia was calculated. All LaVF pts had sustained the infarct more than 6 months before VF. With conventional studies, such as exercise tests, thallium scans or coronary angiograms, no signs of ischemia was found. Perfusion (ml/min/100g) LaVF ( Although ischemia was thought to be sufficiently ruled out, the significantly larger CV in LaVF compared to HVs suggests that active ischemia still plays a role in the development of ventricular fibrillation in these patients. This is of importance as it may result in a different selection of therapy. Moreover, it emphasizes the importance of the more accurate assessment of myocardial ischemia with PET. In thrombolysed myocardial infarction (MI) akinesia of the infarct area (IA) can be related either to myocardial necrosis or to viable but hypoperfused myocardium that can recover its function after revasanlarization. 12 pts. (11 males, 1 woman; mean age 56 +_ 6 years), with recent MI ( 7 anterior, 5 inferior) treated by thrombolysis underwent basal 2D echo (11 segment model; score of the IA from 0 = normal to 3 = dyskinesia) and TI 201 stress-redistribution (ST-RD) ECT (score from 0= normal to 3= severe reduction or absent T1 uptake) within 2 weeks from MI. All pts. underwent successful (<50 % residual stenosis) PTCA of the stenotic or occluded MIrelated coronary artery within 1.5 month from MI and had a new baseline 2D echo and TI 201 ECT 2 months after PTCA. After PTCA 6 pts ( GROUP i) showed fanctional improvement in > 50% of basally akinetic sgts., with decrease of wall motion score (WM) of the IA from 5 -+ 2.7 to 1.8 +_1.3 (p <.01), while 6 pts. ( GROUP 2) hadn't any significant improvement in WM score of the IA (from 6 -+1.8 to 5.3 _+ 1.9; ns In group 1 the ST-T1 score of the 1A improved significantly from 8.5 +-4.6 before PTCA to 4 -+2.3 (p <.05) after PTCA, as did the RD score (from 4.6 + 3.1 to 3.5 -+ 2.1); on the other hand, after PTCA ,group 2 pts showed no significant improvement in ST (from 8.2 +_3.9 to 6.3_+3.4) or RD (from 7.1 -+ 3.1 to 5.7 _+ 3.6) TI score of the IA. In recent thrombolized MI, the recovery of perfusion and function of the akinetic segments in the IA, after PTCA of the MI-related coronary artery, is accurately predicted by the prevalence of reversible ST-RD defects in the IA. No significant improvement can be expected when a high fraction of severe irreversible ST-RD defects is observed. Likely there is no need of reinjection. In recent studies we found many segments with persitantly pathologic FA metabolism after revascularization which might be due to the kind of the graft. We investigated 21 patients (pts) before and two months after ACB. 58 grafts revascularized (rev) 41 of 49 (84%) territories perfused by a stenosed artery. In the LAD territory revascularization was achieved in 62% by the internal mammary artery (IMA), in 38% by vein grafts (SVG) and 34% of the pts had both, IMA-and SVG-grafts. 200 MBq of IPPA were injected at the end of a submaximal exercise. After exercise SPECT-scintigraphy (ECT-I) was performed which was repeated after 15 min with pts in the same position (ECT-II). Oblique slices were obtained and divided into 5 segments (sgs) which served for quantification. Comparison of sgs of ECT-I before and after therapy served for evaluation of uptake (flow, up) and sgs of ECT-II for turnover (metabolism, met In conclusion, restitution of flow early after reperfusion therapy can be clearly demonstrated by IPPA studies. Many myocardial regions show persitantly abnormal fatty acid metabolism after therapy with no major difference between IMA and SVG grafts. The outcome of the patients in terms of fatty acid uptake and metabolism was best in the case of a combined IMA and SVG therapy. The clinical impact of the rein.iection (REI) in different groups of patients (pts.) undergoing TI 201 stress study remains still uncertain. Aim of the study was to assess whether the REI, performed in pts with first myocardial infarction (MI) treated by thrombolysis ( < 6 h), gives significant additional information compared with the conventional stress-redistribution (ST-RD) T1 ECT scan. ST-RD (4h)-REI (injection just after RD, imaging after 30') -TI ECT was perfumed in 31 patients (pts) 10 + 5 days after a first uncomplicated thrombolized MI ( median age 56 -+ 7, echo E.F.= 51% _+12% ). The left ventricle was divided into 11 segments (sgts). TI uptake in each sgt. was scored by. consensus of two experienced blinded physicians using a 4 point scoring system ( from 0 = normal to 3 = severe reduction of TI uptake I m m e d i a t e thallium-201(TI) reinjeetion following post exercise(Ex) imaging has been proposed as a novel time saving approach for the evaluation of patients(pts) with ischemic heart disease. Purpose: The aim of our study was to establish the clinical value of immediate TI reinjection imaging for the detection of the distinct aspects of lschemic heart disease. A total of 138 pts with undiagnosecl chest pain and documented coronary anatomy were studied. Fifty-six (41%) of the 138 pts had previous myocardial infarction(MI). Of the remaining 82 pts(59%), 24 pts(17%) had low likelihood coronary artery disease(GAD). Methods: TI (75 MBq} was injected at maximal Ex and reinjected (37 MBq) immediately after completing 3 view planar Ex imaging. Resting images were acquired 60 minutes after reinjection. Each set of T1 images was visually and quantitatively analyzed and compared with artedographic findings and left ventdeular wall motion. Scintigraphic detection of stress induced ischemia was based on T1 Ex data in all 138 pts., detection of re~,'ersible ischemia on reversibility of TI defects in 50 pts with proven GAD and previous MI, and detection of viability on sevedty of T1 defects in 168 vascular regions of 56 MI pts. Result~ sen sitivity accuracy Stress induced ischemia n = 138 pts* 91%(84 96) 83%(76-89) Reversible ischemia n -50 pts 93%(82 99) 92%(71-89) V i a b i l i t y n = 168 vessel regions 89%(84-94) 83%(72 93) *Normalcy rate based on low likelihood pts: 21/24 = 88% Numbers between brackets denote the associated 95% confidence limits Conclusion: Immediate TI reinjection imaging shows adequate diagnostic accuracy for the assessment of stress induced ischemia, reversible ischemia, and myocardial viability in pts with ischemie heart disease. These findings underscore the potential of immediate TI reinjection imaging for use in routine clinical pradice. Combining simultaneous assessment of Rbclearance (ExF) with MBF-determination by the argon inert gas-method allowed us for the first time determination of the previously in humans unknown E(MBF)-relation. Therefore Rb-clearance (ExF) was determined with a Siemens ECAT-931-08-12 PET scanner. MBF was measured simultaneously with the argon inert gasmethod by coronary sinus sampling of argon desaturation in 5 patients without indication of coronary artery disease. Mean age was 60.6 ± 7.4 years (2 female and 3 male patients). Measurements were done at rest and during dipyridamol (0.7ml/mg/4min) induced hyperemia. Mean Rb-ExF and argon flow values were 0.33 ± 0.03 ml/g/min and 0.69 ± 0.15 ml/g/min at rest, respectively, and 0.42 ± 0.06 ml/g/min and 1.46 ± 0.23 ml/g /min during hyperemia. The Rb-extraction fraction was derived by dividing Rb-clearance by argon flow values. A fit to the theoretical dependence of the extraction fraction on flow for a two compartment model yields E = PS/(PS+F) , PS=(g.90±0.09)ml/g/min . We conclude that the simultaneous measurement of Rb-elearance and argon flow is a powerful tool for the assessment of the Rb-extraction fraction in dependence on flow in normal human myoeardium. Logistic regression analysis was used to determine whether the addition of Tc-SESTAMIBI myocardial imaging-and left ventricular function parameters or diastolic images could improve the accuracy of TI-201 scintigraphy to predict the presence and extent of CAD in 60 consecutive pts. Univariate logistic regression analysis demonstrated that all Tc,SESTAMIBI visual and quantitative perfusion parameters, gated wall motion studies, diastolic images and TI-201 perfusion parameters were significantly related to the probabilities of CAD, multivessel disease and 3-vessel disease. Using the multiple regression model the 'optimal' combination was stepwise selected. For TI-201, being the visual score of the stress images and quantitative score of redistribution. For Tc-SESTAMIBI, only the visual score of the stress images. Only small and statistically no significant differences with respect to predictive values were seen. Whatever combination of variables of the two protocols were considered, no significant difference with respect to predictive value was found compared to the simple ('optimal') TL-201/Tc-SESTAMIBI protocols. In order to compare stress echocardiegraphy (Echo) with perfasion 99mTc-Sestamibi (MIBI), we have used stress dobutamine to study 110 patients (pts). However, 23 pts were excluded due to inconclusive stress test. The remaining 87 pts, 74 males and 13 females, =57.4+lO years, 56 pts with previous myocardial infarction and 31 with anger. 37 pts (43%) had ¢oronariography with significant lesions. Left ventricle ejection fraction by equilibrium angiocardiogrephy was in the anterior infarction = 32.7+12.7°/,, in the inferior = 51.2+8.3% and in pts without infarction = 53.4+9.5%. Pts were infused with dobutamine until maximal dose of 40mg/kg/min or a new regional wall motion abnormality (RWMA) was detected by Echo or if standard clinical criteria appeared for stopping infusion. No major side effects were referred. However, in 12/23 pts out of the study, the infusion was stopped due to increased BP in 8 and SVE in the others. During the infusion Echo study was performed and 15 mCi of MIBI was administered at test end, with infusion continuing one more minute. SPECT was performed 1 hour later and rest SPECT at 48 hours. MIBI and Echo were analyzed qualitatively, considering 12 segments of left ventricle. We have considered normal segments and two lesions types, namely necrosis ffi irreversible MIBI lesions = stress and rest Echo RWMA and ischaemic = reversible MIBI lesions = stress Echo RWMA. Of a total of 1044 (12 x 87) segments analyzed, 813 (77.9%) had the same classification with MIBI and Echo. The most discordant wall was the anterior (72.5+16.8%) and the most concordant studies were in the patients without previous infarction (86+14%). If we consider myocardial ischaemia, we found only 28% of concordance in a total of 47 pts with ischaemia in at least one of the two methods. Dobutamine stress echocardiegraphy seems to offer an alternative to 99mTc-Sestamibi, in the identification of CAD with a 78% concordance. Our results show, however, a poor match in the detection of ischaemic myocardium, which is the main purpose of the method (28% of concordance). No statistical differences were found related with the infarction localization. However, in pts without previous myocardial infarction we have obtained better results, perhaps because it is easier the valorization of RWMA, when no rest alteration exists, which may account for the principal indication for stress Echo. The aim of the study was to establish if the high dose dip SPECT brings more diagnostic informations than low dose dip SPECT. 32 patients (pts) with coronary artery disease without infarct were examined. Low-dose dip (0,56 mg/kg) was administered i.v. to 18 pts (group I); high-dose dip (0,7 mg/kg) was administered i.v. to 14 pts (group I1.) Administration of dip was connected with minimal exercise, The both groups of pts were matched in age, resting heart rate and systolic blood pressure. All pts underwent two 99m-Tc-MIB[ SPECT studies performed 15 days apart, one after dip administration and another one after submaximal bicycle stress (85% age-predicted heart rate). Agreement in defects size, their type and localization between dip SPECT and stress SPECT was observed in 17 of 18 pts (group l) and in 13 of 14 pts (group II). The following side -effects were observed: ST segment depression in group I -2 pts, in group II -3 pts; chest pain in group I -2 pts, in group II -4 pts. Headache, dyspnoe, dizziness and nausea in group I -3 pts, in group II -7 pts, 1. High dose dip SPECT do not bring more diagnostic informations than low dose dip SPECT. Myocardial ischaemia and anginal pain (ap) in patients (pts) with normal coronary arteries and no other heart abnormality is supposed to be due to limited flow reserve of small vessels. Perfusion defects on planar thallium scans are frequently reported in this group of patients although the limitation of the method obscure their interpretation. Single photon emission computed tomography (SPECT] has improved the nuclear technique to diagnose and localize perfusion defects. 17 pts (age±sd: 42.6±8 0; F/M: 9/8) with ap. positive exercise stress test, normal coronary arteriography and no other heart abnormality were included. Myocardial perfusion was examined with Tc-99m-MIBI SPECT technique (gammacamera DIACAM, SIEMENS]. Perfusion was assessed in 9 segments using semiquantitive scale. Abnormal perfusion was detected in 12 pts (70Z). Of the overall 153 segments, there was fixed defect in I0, reversible in 8, and paradoxal deterioration of rest perfusion in 25 segments. The defects were localized mainly in the territory left anterior descending artery (33 segments) and right coronary artery (9 segments). There is a high proportion of perfusion defects on SPECT scan in patients with mierovascular angina with no consistent pattern. There is a numerous group of patients with paradoxal perfusion deterioration at rest mainly in the territory of the left anterior descending artery. The aim of the work is to eslablish if the quantitative (QUANT) results of LV perfusion studies performed before revascularisation (PRErev) allow to predict the perfusion after revascularisation (POSTrev). Thirty five pts were studied PRErev and POSTrev with Tc-99m-MIBI SPECT (according to 2-days protocol) in stress (S) and rest (R). CABG was performed in 23 pts, PTCA in 10 !0ts; 2 pts died before planned CABG. The study assessment was performed qualitatively (visual evaluation of LV sections and BULL'S-EYE maps) and quantitatively (normative evaluation of BULL'S-EYE maps). The results of the QUANT evaluation were 4 numbers: the area of the perfusion defects in S and R (As and At) and the perfusion level within the defects in S and R as a fraction of the normal perfusion level (Is and Ir). The perfusion defect was defined as DEFs=As(Iqs) in S and as Dt3Fr=Ar(1-Ir) in R. Also S-R perfusion improvement was calculated as DEFr-s=DEFr-DEFs, Linear correlation was investigated between DEFs, DEFr and DEFr-s PRErev and POSTrev. Results: 1) The QUANT results were rejected in 13 pts because of inaccuracy of the BULL'S-EYE technique in cases of completely unperfused apex or because of falsepositive results in cases of very short but normally perfused septum or because of false-negative results in cases of long underperfused septum 2) In 2 patients who died before revascularisation, The relative hypoperfusion at lateral wall due to septal hypetrophy on the myocardial perfusion scans(MPS) have been previously reported in patients(pts) with hypertension. In our study, we aimed to investigate the frequency and level of lateral h y p o a c t i v i t y on MPS in h y p e r t e n s i v e ( H T ) pts e i t h e r w i t h septal hypertrophy or not. T12°I SPECT studies were performed in 33 HT pts and 27 normotensive(NT) pts who have normal coronary angiograms. The images w e r e e v a l u a t e d by q u a n t i t a t i v e method(Bull's eye) and lateral to septal(L/S) count ratios. Bull's eye demonstrated fixed perfusion defect in ii HT pts that 6 of them showed septal hypertrophy on echocardiographic imaging. L/S ratios were found as in following table: Stress Rest HT pts (33) 1.02±0.09 1.01±0.08(p<0.01) NT pts (27) 1.11±0.09 1.09±0.08(p<0.01) Bull's eye defect 0.976±0.08 0.960±0.074 The ratios of L/S in HT pts were found lower than NT pts as statistically significant. It was concluded that the lateral fixed defects in HT pts which may mimick myocardial infarction on MPS have to be kept in mind during evaluation of MPS. On the other hand, fixed defect at lateral wall may be seen in HT pts without septal hypertrophy and we think that more studies are necessary to explain the causes of the lateral wall defetcts in HT pts. The aim of the study was to search for an objective criterion of healing diabetic foot ulcer, using intraarterial, simultaneous injection technique of Tc-99m MAA (MAA) and Xe-133 (Xe) to identify perfusion and venous capillary blood-flow of lesion side. 12 patients (pts.) with risk foot and, or diabetic foot ulcer who had clinical diagnosis of grade (G) 0 to 4,were included , after getting their informed consent. All pts. received intra-arterial administration of 1 mCi of MAA (particule size:10-60 ~tm and max. particule amount : 5 x 104 ) and Xe ( 0.5 mCi ) simultaneously. No complications or side effects were observed. A two step dynamic acquisition protocole was applied in dual isotope energy window (1 sec. acq. time for 150 frames and 60 sec. for 10 frames). All images recorded in 64 x 64 word matrices. Whole-body (WB) images were also obtained within an hour after tracer administration. Ulcer zone, surrounding hyperactive area and gangreneous tissue were evaluated as considering MAA uptake of normal (N), hot (H), cold (C), and Xe washout curve patterns of normal (N) fast (F), moderate (M) or poor (P). In , G-0 (1 pt.) Xe and MAA uptake pattern was normal. In 6 pts. with G-1 disease MAA uptake was [n H pattern and 5 of them had F Xe washout, a case with N Xe washout pattern was found to have two focii in healing process. In a case with G-2 disease diffusely H MAA uptake and M Xe washout was observed due to the serious infection. In a G -3 pt, same uptake pattern of MAA and F washout of Xe was detected. In 3 cases who had G-4 disease H / C MAA uptake pattern and F / P Xe washout were noted. In WB images pulmonary uptake of MAA was also searched as an indicator of arterio-venous (A-V) shuntings. Except for apt. with G-0 disease, in all cases A-V shunts were detected in diabetic foot. Shunt ratios were quantified as 22.8 + 14.1 and 10.3 -+ 6.7 in disease side and intact zone, respectively (p <.025). In conclusion, H MAA uptake pattern and N or F washout of Xe indicate healing potential of diabetic ulcers. M or P Xe washout curves and mixed uptake pattern of MAA (H/C) indicate serious infection and gangreneous nature of the lesions. Combined use of MAA uptake and Xe washout gives an objective criterion to evaluate healing potential of diabetic foot ulcers. Aim of this study was to examine if myocardial activity of Tc-99m-sestamibi is stable after injection. Sestamibi myocardial scintigraphy was performed in 15 consecutive patients with angiographically proven coronary artery disease (2-day-protocol; 2 x 300 MBq). After submaximal bicycle exercise, SPECT was performed 5 min (early) and 2 hours (late) after injection. The rest study consisted of one scintigraphic acquisition about 100 min p.i. The left ventricular myocardium was divided into six segments and sestamibi uptake was scored semiquantitatively by 2 experienced observers using a 5-point grading system. In all studies a sufficient image quality was achieved for interpretation of slices. However, image quality was affected by hepatic activity in early SPECT in some patients. A total of 114 segments was analysed. In 69/114 segments initial defects were detectable. In 72/114 segments no difference in score could be registered between early and late SPECT. In 35/114 segments the score improved within the first 120 min p.i. (fill-in of initial defects). The early fill-in could be correlated with a significant narrowing of the corresponding coronary artery in most cases. In 7/114 segments a deterioration in score from early to late SPECT was documented (tracer wash-out); in 6 of these 7 segments the score returned to its initial value (n=2) or improved (n=4) in the rest scan. In 1 segment sestamibi was washed-out between early and late SPECT and tracer uptake remained low in the rest study. A clear correlation between tracer wash-out and coronary anatomy could not be detected. Myocardial Tc-99m-sestamibi activity is not stable after injection: Early tracer washout can be documented as well as a fill-in of initial defects. SPECT should be performed immediately after exercise; later acquisitions may be performed if image quality is poor. The Silent Arrhythmogenic Cardiomyopathy (SAC) includes an inhomogeneous spectrum of life-threatening arrhythmogenic cardiac diseases without valuable functional impairment. In order to establish the efficacy of 123I-MIBG scan as diagnostic marker in SAC 18 patients (18 males -0 females, aged 18 -45 yrs), with high physical performances, "clinically normal" heart, and hypercinetic ventricular arrhythmias (9/18 with sustained ventricular tachycardia a/o ventricular fibrillation,2 of them resuscitated) were studied and compared with a control group of 5 subjects.In all of them we performed: a) a complete cardiological study comprehensive of echocardiography M and 2D mode; b) tomographic scan 4 hours after injection of 370 MBq of 123I-MIBG and 1 hour after injection of 740 MBq of 99mTc-MIBI with tomographic camera Orbiter Siemens, HR collimator,64 matrix, 64 views, 180 ° rotation. Both data were reconstructed by filtered backprojection (SLH, cut off: 0.5 MIBG, 0.8 MIBI).The Cardiac Magnetic Resonance was also performed in 9/18 and the Coronarography in 7/18. All the investigations were normal in the control group; in the other patients the cardiological study detected a cardiomyopathy in 12/18 (6 Right Ventricular Arrhytbmogenic Disease, 4 Biventricular Cardiomyopathy, 1 Left Ventricular Dilated Cardiomyopathy, 1 Coronary Artery Disease [CAD]).I 1/18 patients showed focal defects with MIBG: 6 in the apex, 2 in the anterior wall, 3 in the lateral, 4 in the septal and 7 in the inferior. With MIBI we observed defects in 4 patients: 2 defects in the anterior wall, 3 in the lateral and 2 in the inferior.In all cases, except one (CAD), there is a mismatch between MIBG and MIBI defects.Versus SAC the MIBG scan has demostred: Sensitivity 83.3 %, Specificity 83.3 %, Predictive Positive Value 90.9 %, Predictive Negative Value 71.4 %, Accuracy 83.3 %. These preliminary findings suggest that the MIBG may be a good marker to evaluate defects of the cardiac adrenergic innervation in SAC and that it may play an important role in the difficult detection of these cardiac diseases. The aim of the study was to compare adrenergic innervation and myocardial perfusion in diabetic and non-diabetic patients who had serious coronary artery stenosis. 1-123 MIBG, a guanethidine analague was used for scintigraphic assesment of myocardial symphatetic innervation. A total of 19 coronary artery disease (CAD) patients who had documented multivessel disease in coronary angiography, 8 diabetics (D) and 11 non-diabetics (ND) were included, prior to by-pass surgery. After a 30 rain. resting period, all patients received 110 Mbq of 1-123 MIBG. SPECT data and planar views were obtained starting at 15 minutes and 4 hours after the injection. In all patients, rest -T1-201 SPECT study was also performed within two days to asses myocardial perfusion and viability. Heart to mediastinum (H/M) 1-123 MIBG activity ratios in early and delayed views were quantified.. T1-201 and 1-123 MIBG SPECT data were compared in respect of defect size, in tomographic planes and polar maps. In D patients globally poor cardiac uptake of 1-123 MIBG was observed. In all patients segmentally larger denervative areas in disease sites were identified when compared to T1-201 perfusion defects. A statistically significant difference in H/M ratios of 1-123 MIBG uptake was detected between D and ND patients in early and delayed views; D: 1.72 + .11, ND: 2.13 + .22, D: 1.51 + .24, ND: 2.30 _+ .15, P< .005. However , it has not reached a statistically difference, a slight increase in 1-123 MIBG uptake in ND patients and a decrease in D patients was noted in delayed views. We conclude that, D CAD patients had significantly poor sympathetic myocardial innervation when compared to ND's without any relation with the severity of CAD. Further studies are necessary to determine the clinical importance of viable but denervated myocardium in D patients in respect of prognosis after coronary by-pass surgery. G. Cantinho, E. Silva, T.Martins, A.L Santos, L.C. Oliveira, F. Gadinho Instituto de Medicina Nuclear, FML and Servi~o de Cardiologia, HSM Lisbon, Portugal Metaiodobenzylguanidine labeled 131I (MIBG), as an analogue of norepiaephrine, localizes in the adrenergic neurons, enabling determinations in viva of disturbances in integrity and function of the sympathetic nervous system (SNS)in the heart. MIBG is taken up in the post ganglionic presyaaptic vesicles, remaining intra-vesicular representing the true intraneuronal uptake. The non specific extraneuronal uptake is of little afinity, with a rapid washout. The aim of our study is to evaluate SNS MIBG uptake in patients with mitral valve prolapse syndrome (MPS) and it's relations with arrhytmogenic activity and plasma cathecolamines levels.We studied 17 patients (pt) with MPS, mean age 49,5±12,8 years old, It female and 6 male, all with ventricular disritmias. In 13 the sympathetic adrenal activity was increased (mean orthostatic plasma catecolamine = 867.9~-947.6, N<400pg/ml), all without heart failure.After thyroid blocade, all pt were injected iv. with tmCi of MIBG. Sets of scintigraphic planar anterior images were performed at 4 and 24 hours. Data was collected over 15ran in a 128x128 pixel matrix. Uptakes in the heart (H), lung (Lu) and liver ( Statistical analysis using paired t Test didn't find any differences between Lu/Lu and H/H (4 and 24h), but there was a significant difference between Lu4/Lu24 and Li4/Li24 compared with H4/H24 (p<0.00l). Statistical differences were found between LulH and Li/H at 4 and 24h (p<0.05). No inter-patients differences in heart, lung and liver washout was tbund, suggesting a true neuronal uptake. No correlation was found between plasma cathecolamines concentration and MIBG uptake, suggesting autonomic function. In 88% of pt, the MIBG uptake normal results suggest normal pre-sinaptic function. In only 2 pt (12%) the results did suggest adrenergic nervous system disfunction. H. Valette, B. Mazi~re, C. Loc'h, C. Fuseau, A. Syrota. Physiologie CHU Bic~tre and SHFJ-DRIPP-CEA, Orsay, France. Beta-adrenergic antagonists are increasingly used for the treatment of congestive heart failure. Nevertheless, the effects of these drugs on myocardial presynaptic sympathetic uptake-storage function are not well known. Therefore, the effects of the fSl-antagonist metoprolol on the presynaptic neuronal uptake of MBBG, a norepinephrine analog, were studied in normal rabbits. This species was chosen because previous study has shown that the rabbit heart, like the human heart, has little capacity for non-neuronal uptake of MIBG, and consequently appears to be amore suitable model than rat to study neuronal uptake. Sixteen rabbits (mean weight: 2.5kg) were studied: 8 control and 8 pre-treated with metoprolol (0. lmmol/kg ip twice a day for one week). Initial myocardial uptake of MBBG (6MBq) was measured 30 rain after injection of the tracer. Rabbits were killed with an overdose of pentobarbitaI, their heart quickly removed, dissected and the radioactivity counted. Results (mean value + sd in %kg dose/g; left (LV) and right (RV) ventricles): LV RV Control (C) 5.60+0.74 4.42+0.75 Meloprolol (M) 3.94+1.27 3.09+1.00 p (Nest) 0.006 0.01 Plasma Norepinephrine (NE, pg/ml) remained unchanged and epinephrine (E) remained unchanged: NE-C= 245+55, NE-M= 231_+45 pdml and E-C= 18_+4, E-M= 19_+6 pg/ml, respectively. The significant decrease (30%) in myocardial MBBG uptake cannot be explained an increased release of norepinephrine, the release being reduced by/,Lblockade. The reduced MBBG uptake cannot be related to a decrease in coronary blood flow which has been show to be invariant after/3-blockade in awake animals. These results suggest an interaction between metoprolol and the norepinephrine uptake one carrier. The purpose of the study was to i d e n t i f y the relation of positive antimyosin scan to onset of symptoms of congestive heart f a i l u r e (CHF), myocardial f i b r o s i s (MF) and response to medical treatment including digoxin, ACE inh i b i t o r s and furosemide. Seventeen patients (pts, 13M/4F) 43±12 yrs suffering from idiopathic cardiomyopathy diagnosed by endomyocardial biopsy, underwent antimyosin scan, c l i n i c a l and hemodynamic evaluation and q u a n t i t a t ive estimation of the MF. In 9 pts (group A) the antimyosin uptake r a t i o in the cardiac and right lung regions (H/L) were >1.6 (2.01±0.35) and in 8 pts (group B) <1.6, (1.43±0.05,-p<0.005). The duration of heart f a i l u r e symptoms in group A was 30±34 months (range, 1.5-108) and in group B, 18±19 months (range, 4-62, p=NS). There was no c l i n i c a l or hemodynamic difference between the 2groups. The proportion of MF was 7.6±5.3% in group A and 3.6±2% in group B (p=NS). NYHA functional class was reduced by medical treatment by 1.5±1.2 in group A vs 0.4±0.5 in group B (p 1+ after BV). 9 pts had a baseline LVEF impairment < 55% (47±8%, G1), and 9 pts had normal LVEF (63±7%, G2). Between the two groups, neither age, sex, baseline HR (bpm), EDV, and echographic mitral valve area (VMA, cm 2) were , different: pre-BV HI~ LVEF EDV PER PFR MVA G 1 76-,-12 47+8** 150±22 2.53±0.8 1.87+0.5" 1.06-,-0.2 G 2 67+11 63+7** 150±32 3.19±0.8 2.27+0.3* 1.01±0.2 * p< 0.05, ** p<0.0005 between groups. Before and after BV, MVA was correlated with PFR (r=0.51, p<0.05) but not with LVEF. After BV, no significant difference changes in HR and EDV were observed in both groups. In contrast, LVEF, PER, and PFR improved significantly only in GI. I PER I PFR I MVA I I cl I 5e±7"** 13.15±0.5"12.46±0.6.*12.21±0.3.**1 I G2 I 65±4 13.41±0.6 12.74±0.6 11.99±0.3"** I * p< 0.05, ** p< 0.005, *** p<0.0005 from baseline. Conclusion: successful BV of MS increase LVEF in pts with baseline systolic dysfunction, independently of the improvement in filling parameters and preload. The aim of this study was to evaluate the effect of hypertension on the left ventricular systolic and diastolic functions and the acute effect of single dose long-acting nifedipine on these functions by the use of radionuclide ventriculography. Twentyfive hypertensive patients (13 M, 12 F; mean age: 48±11.2) and 19 normal control subjects (9 M, I0 F; mean age: 35.2±11.2) were studied. Equilibrium Radionuelide Ventriculography (ERNV) studies in hypertensive and normal subjects were performed by labelling the RBC in vivo..In hypertensive patients, following basal ERNV study, 20 mg of long acting nifedipine were administered orally and ERNV studies were repeated at 1.5 and 4 h. For the normal subjets only basal ERNV study was performed. When the left ventricular systolic and diastolic function indices in hypertensive and normal groups were compared, diastolic parameters such as PFR and TPFR were copletely abnormal in the hypertensive group (p<0.05). But for the systolic parameters no significant difference were found between these groups (p>0.05). When the hypertensive patients were classified based on left ventricular hypertrophy no significant difference between systolic and diastolic indices were found (p>0.05). The acute effect of long acting nifedipine on left ventricular systolic and diastolic function in hypertensive patients was a significant improvement of these functions. In conclusion, we found that diastolic parameters were significantly impaired in hypertensive patients and nifedipine has a positive effect oh both systolic and diastolic functions. Aim of the study was to assess the influence of parameters of left ventricular function on pulmonary thallium uptake. A further aim was to investigate inhowfar pulmonary thallium content can be accurately quantitated from the anterior SPECT projection and to determine the pattern of the intrapulmonary thallium-201 distribution. (1) In 24 patients myocardial SPECT (30 sec/frame, 64x64 matrix) and planar anterior imaging of the thorax (acquisition time 120 sec, 256x256 matrix) were performed. The lung heart ratio (LHR) was determined from the anterior SPECT projection and from the planar anterior scintigram; the values of both methods were intercorrelated (r=0.993; p<0.001). (2) Regional pulmonal thallium-201 distribution in the right lung was examined in 20 patients without evidence of coronary artery disease. A lower thallium activity was recorded from the apex of the lung as compared with the basal portion. (3) In another 41 patients a radionuclide ventriculography (RNV) was performed within four weeks after myocardial SPECT. The LHR was negatively correlated (p<0.05) with peak ejection rate at rest (r=-0.34), peak filling rate during exercise (r=-0.41), left ventricular ejection fraction during exercise (LVEFex) (r=-0.41), and maximal heart rate during exercise (HRex) (r=-0.44).In the multiple regression analysis LVEFex and HRex showed the strongest relation to LHR (R2=0.42; p<0.001). Using the regression equation the exspected LVEFex was calculated using HRex and LHR as parameters. This calculated LVEFex correlated with the actual LVEFex which was derived from RNV (r=0.53; p<0.001). In conclusion, (1) pulmonary thallium can be quantitated from the anterior SPECT projection with sufficient accuracy, (2) a pulmonary thallium gradient exists from the apex to the basis, and (3) Blood volume was measured using method adjusted in our laboratory as a by-product during routine equilibrium radiornuclide ventriculography With 740 MBq Tc-99m-human serum albumin twice: i) before rHuEPO treatment and 2) at the time when target hemoglobin (Hb) reached I00 g/l. Time elapsed to reach target Hb was 3.4 ± 1.4 months; Hb increased from 73 ± 6 to iii ± ii g/l, (p<0.0001). Red-cells volume was significantly increased from 16 i 3 prior therapy to 26 ± 6 ml/kg (p<0.001) after therapy. Despite significant decrease in plasma volume (53 ± i0 before vs. 48 ± ii ml/kg after, p<0.01) total blood volume was increased from 69 ± 12 to 73 ± 16 ml/kg (p<0.01) after correction of anemia. Significant fall in cardiac index was found after treatment due to reduction of left ventricle end-diastolic volume (p<0.01) and heart rate), while ejection fraction and blood pressure remained unchanged during rHuEPO treatment. We concluded that increase in red-cell volume occurs within short time period through correction of anemia, along with decrease in plasma volume, but increase in total blood volume. Tc 99m MIBI acquisiticns. Ninety-nine male patients with a low inferior wall o~mt in the supine stress images ~erw~nt stress and rest a~i~ in supine and prone positifm ~ively. For each study, values dspicting the inferior, amterior, septal and lateral wall counts were extracted from a medioventricular, normalized to one, cirom~erential profile. ~he inferior and septal(resp. anterior and lateral) walls were significantly better visualized in the prone (resp. supine) than in the supine (resp. prone) position (S~rl~nt paired t-test < 0.001 < 0.001 < 0.01 Amzng the 54 pat±ants with a supine stress inferior co%at less than 0.8 and a supine stress/rest ratio less than 0.9, the ~e ratio, wh~ ~mpered to the s~pire one, increased by more than 5% in 34 p~tients and was greater than 0.95 in 20. In ccnclusicn, with Tc 99m MIBI, as with T1 201, the my~xzardial oou~t distrJb/tJrn differs b e~ sl~pine and prone position, especially in the inferior wall. 9~e inferior ~/rest differences are reck~ed in prone position. Prone pcsiticn is preferable for the inferior and septal %~lls interpretation while supine i:ositJmn is pref~le for the anterior and lateral walls. Osmbining both positicns wou/d probably ~t a misleading interpretation. The relative regional uptake in Pr was higher (p < 0.01) inferior and infero-septal: in D apical and basal, in S apical and middle, in NGSPET in all slices. The highest Pr/Sup difference was in D, the smallest in S, more pronounced in (A) than in (B). Pr imaging improves the accuracy of inferior wall abnormalities in 99mTc-MIBI SPET by reducing attenuation artefacts. The influence of Pr positioning is more prominent in "normal" pts than after MI and is not to the same degree in D and S (D > S). The quantitative parameters (i.e."wall-thickening") may be differently influenced in Pr and Sup. Recent data suggest that the ratio of counts in the left ventricular (LV) cavity to that in normal myocardium (C/M ratio) of thallium (T1-201) scintigraphy can be used to assess LV dysfunction. This study examines the relation between the C/M ratio and the LV ejection fraction (EF); furthermore the influence of T1-201 activity in blood, myocardial T1-201 uptake and LV size on the C/M ratio was determined. Twelve patients (9 with previous infarction) underwent T1-201 SPECT at rest and angiography. To calculate C/M ratios, 2x2 pixel ROIs were placed in the center of the LV cavity and on the myocardium with the highest T1-201 activity. Venous blood samples were drawn at the start of SPECT imaging to measure "1"1-201 activity; LV diameter (as a measure of LV size), extent and mean severity of perfusion defects were determined from SPECT images. Multiple regression was used to delineate which of these factors contributed significantly to the C/M ratio. EF varied from 13 to 80%. The C/M ratio showed a good correlation With the EF (r=0.90, p<0.001). ANOVA Thus, the C/M ratio shows a good relation with the LVEF and is mainly influenced by LV size and the severity of the perfusion defect, suggesting that spill-over of T1-201 activity from myocardium to the cavity determines the C/M ratio. It has been described that image quality of F18-fluorodeoxyglucose (FDG) is poor in patients with diabetes mellitus. In the present study we investigated the image quality of FDG SPECT studies during hyperinsulinemie euglyeemic clamping in 10 patients (pts) with chronic coronary artery disease (CAD) and in 10 pts with CAD and diabetes mellitus type II (DM H). Levels of lactate (LA in retool/l), free fatty acids (FFA in mmol/1), glucose (GL in mmol/1) and insulin (INS in mU/l) were measured at the start and after 1 hour of clamping. The image quality was expressed by the myocardium-to-blood-pool (M/B) activity ratio (determined from short-axis slices Baseline levels of GL and FFA were significantly higher in the DM H group. One hour clamping increased INS levels significantly in both groups, and decreased FFA levels significantly in both groups but FFA levels remained higher in DM II pts, possible due to a relative insulin resistance. Also GL remained higher in DM H pts. Despite higher FFA levels image quality was not significantly lower in DM H pts. Thus, hyperinsulinemic glucose clamping may be advocated in DM II pts because it results in an image quality comparable to that of non-DM II pts. The use of 1231-16-Iodo-3 methyl hexadecanoic acid (IMHA) has been developped in order to evaluate the residual myocardial viability after a myocardial infarction. The best time for imaging is a matter of discussion. The aim of this study is to compare the relative myocardial distribution on IMHA S.P.E.C.T. 15 minutes and 45 minutes post intravenous injection. Eleven patients were studied after a myocardial infarction. In each patient, S.P.E.C.T.was obtained 15 and 45 minutes after injection of 148 MBq of IMHA at rest. Thallium S.P.E.C.T. was also obtained on a separate day at stress, redistribution and reinjection. Nine segments were quantitatively analysed by two observers on each tomogram set. The myocardial uptake was expressed as a percentage of the segment with the higher uptake. The uptake of IMHA was calculated in three groups of regions according to their uptake of thallium at reinjection (<60%, 60% -80%, >80% ). IMI-I uptake in the three groups was as follow : IMHA Uptake (%) TI uptake (reinjection) t 5 rain 45min <60% (12 segments We focused on the use of dynamic hepatobiliary scintigraphy /DHbSc/ in the follow-up of liver perfusion in patients with prehepatic portal hypertension /PPH/. Parameters of 99mTc-HIDA transport rate were evaluated on timeactivity curves in a liver region of interest. The study was based on the presumption that changes in extraction of radioactive pharmaceutical /RP/~ by the liver and thus the shape of liver curve at DHbSc in the PPH patients with intact liver parenehyma correlate with changes of blood flow in the liver. This presumption was verified experimentally in dogs before and after artificial induction of PPH, and in the group of 23 PPH patients with either spontaneously developed collaterals or established portosystemic /PS/ shunt. In animal experiment% the curves of PPH-induced dogs showed a delayed RP transport. Similar liver curve pattern was observed in PPH patients with spontaneously developed collaterals. In patients with PS shunt the pattern of liver curves was close to normal values. The results obtained allow to conclude that patients with PS shunt have a better liver perfusion than patients with spontaneously developed collaterals. Hepatobiliary scintigraphy seems to be a suitable indirect marker of the state of liver perfusion in patienst with PPH. It allows the follow-up of the disease and selection of adequate therapy. Substantial loss of liver function is associated with increased postoperative mortality. The purpose of this study was to assess the predictive value of ABT for postoperative mortality. We studied 1491 patients between January 1, 1990, and December 31, 1993, with elective abdominal surgery. In all patients liver function was assessed by ABT prior to surgery. All over mortality rate was 5.8 % (87 pt TIPS-procedures are performed with an increasing frequency, and they are follwed by profound changes of liver hemodynamics; however, the role of HPS in these patients (pts.) has still to be established. By means of time-activity curves after IV bolus injection of 555 Mbq Tc-99m-pertechnetate we evaluated arterial and portal blood flow in the liver and calculated the relative portal perfusion index in 26 pts with portal hypertension [19 m; 7 f; mean age, 52 (range, 23-81) y; diagnoses: ethylic cirrhosis (cirrh.) 17 pts, post-hepatitic cirrh. 6 pts, primary biliary cirrh. 2 pts, cryptogenic cirrh. 1 pt]. Before TIPS, the relative portal blood flow was significantly reduced compared to normal controls [mean, 30 (8-56) %; normals a 60 %]. 13 (5-20) days after TIPS, up to now 7 pts. were reevaluated and showed a further reduction of portal flow [mean 47 (31-74) % of pretherapeutical levels] in 5 pts, while there was no significant change in 2 pts. Our preliminary data show that (I) HPS can be sensitively used for the monitoring of TIPSinduced alterations in hepatic perfusion, and (2) after TIPS relative portal perfusion is further decreased in some patients when compared to pretherapeutic levels. The objective of our investigation was to compare split functions in hepatobiliary scintigraphy by means of quantitative biochemical liver tests in patients with cirrhosis (according to Child classification A and B). We investigated 37 patients: 18 siJffering from biliary cirrhose, 7 from alcohol abuse and 12 from various other forms of liver cirrhosis. We applied 80 to 150 MBq Tc-99m-bromofenine utilizing an own aquisition and processing program for quantitative hepatobiliary scintigraphy. The half live of uptake (HLU) as a clearance equivalent and the mean parenchymal transit time (MP'i-I) were calculated. Biochemical liver tests were: Imidocyanine green clearance (ICG), Antipyrine clearance, and Mono-ethyl-glycine-xylid concentration. A high correlation was found between all biochemical liver tests (p 0,05) f r o m CS, Also, in ~I,, E T (~8min+/-8.5), E F (73.7Z+/-I0,7) a n d ER (2.02Z/min+/-0,22) didn't differ from CS a n d LPG. In conclusion, after total gasirectomy with vagotomy and excluded duodenal transit, impairement of the GB motility early and recovery of the physiological contractile function late after operation might be attributed to the establishment o~ the hormonal mechanisms (CCK). In the patients with partial gastrectomy, without vagal denervation and preserved duodenal tranzit, GB motility remains undisturbed. The edministratJon of erythromyoin and other macrolides may produce gastrointestinal dose-dependent side effects due to a contractile activity of the smooth muscles. Augmented erythromyoin (AE) is an amorphous form of erythromycin ethylsusoinate, with a bioavailabitity twice better than standard erythromycin ethylsoocinate (SE). AE 500mg has been shown to be as effective as SE lO00mg, but its tolerance was not evaluated. The aim of this study was to evaluate the prokinetio activity of these two formulations compared to a placebo on gastric emptying using a sointigraphic double isotope technic. This randomized double blind controlled study was performed on 12 male healthy volunteers. Each subject was alternatively given AE (500 rag), SE (lOOmg) and placebo per os during a meal labelled with Tc-99m (solid) and In-111 (liquid). Anterior and posterior 60 secimages were acquired in supine position over 4 h, and solid and liquid Tl/2 values were calculated after correction for decay from exponential curve fitting, Clinical tolerance was also evaluated with a semi-quantitative score, Serum concentrations for each product were determined by microbiological method at 0h15, Oh30, lh, 2h, 3h, 4h, 6h, 12h after dosing. Statistical analysis was performed using ANOVA. Results : Tl/2 solid (rain) Tl/2 liquid (min) AE 500 mg (n=12) 88 + 22 ** 67 ± 17 ** SE 1000 mg (n=12) 94 + 25 ** 70 ± 20 ** Placebo (n=I2) 130 ± 38 85 ± 24 ** p 25 % and > 15 % at 4th and 7th days respectively. Results: 1) ileal resection: All patients showed a very diminished abdominal retention at 4 and 7 days ( values ranging from 0 to 3 %). Two of them were treated with cholesteramine and reduced the number of depositions to 1-2/day. 3 out of the 4 remaining untreated patients did not show any change in their voiding frequency. 2) diarrhoeic syndrome: 6 out of the 11 patients showed a marked decrease of Se 75 abdominal retention at 7 days p.a. (range: 0-8 %). Four of them were treated with cholestiramine and reduced the voiding frequency to 1-3 times/day. The other two patients improved with diet. In the remaining 5 patients with normal ARA, reduction of voiding frequency was obtained eithe~ by diet and methylcellulose treatment or was selflimited. In summary: Though the short number of patients studied it seems that patients with diarrhoea and abnormal Se75-HCAT test should be treated with cholesteramine, while if the test is normal other treatment should be looked for. The aim of the work was to study the clinical usefulness of lllIn-IgG in diagnosis and in evaluating the extension of IBD. 15 patients (8 males), mean age 46.8 years have been studied. IED was suspected in all cases and diagnosis was obtained by endoscopy and/or surgery. About 1 mCi of 111In-Human plyclonal-IgG and 5 mCi of 99mTc-HMPAO labeled autologous leucocytes was simultaneous administered to all patients, subsequently abdominal and caudo-craneal scans were obtained at 30 min, 3-4 h and 18-24 h p.i. Images were evaluated by 2 independent observers knowing only the clinical suspicion of IBD. In 10 patients IBD was diagnosed. All showed a positive leucocyte scan and only 7 were positive in the IgG scan. In the remaining 5 patients, in whom IBD was discarded, both IgG and leucocyte scans were normal. Sensitivity and specificity were 100 % for leucocytes and 70 and 100 % respectively for IgG. Concerning extension of the disease, the leucocyte scan localized 21 involved segments while only 9 were identified by the IgG (all were also seen in the leucocyte scan). The activity in the involved segments was always lower in the IgG scan. In conclusion: lUIn-IgG seems to be a valuable, but less 99~ HMPAO sensitive method for the diagnosis of IBD than Tcleucocytes. The method may be use full when leucocyte labeling is not avaliable or to avoid blood handling in AIDS, ... Nevertheless it does not seem accurate accurate to evaluate the extension of the disease. Five p a t t e r n s of colonic transit were identified. The diagnosis of human thrombi still fails to satisfy the criteria of simplicity and non-invasiveness. In 10 patients with deep leg vein thrombosis, in 5 patients with Cimino shunt thrombosis, in 3 patients with vena cava superior thrombosis and in 5 patients with thrombophlebitis the in vivo biodistribution and fibrin localizing capacity of 123I-labeled recombinant human tissue type plasminogen activator (rh-tPA) were investigated. After labeling, in vitro binding studies with platslets indicated the same binding behavior and biological activity of unlabeled and 123I-labeled rh-tPA. 1~3I-rh-tPA bound to a single class of high affinity binding sites indicating >90% ligand specificity. After i.v.-injection to patients (200 MBq/2 mg) organ distribution studies demonstrated that the early rapid uptake of 123I-rh-tPA occured exclusively in the liver. In all patients with deep venous leg thrombosis or Cimino shunt thrombosis 123I-rh-tPA scanning provided excellent imaging of venous thrombi, whereas thrombi of the vena cava superior could not be detected. ~3I-rh-tPA rapidly accumulated in clots within 5 minutes after injection. As jugded by ultrasound and/or phlebography no false positive images were recorded. Blood activity declined rapidly within the first minutes after injection exhibiting a half-life of 6.3±2.1 minutes. Thereafter, slow elimination occured with a terminal half-life of >20 hours. In twelf patients, :nIn-oxine-platelet imaging, 123I-plasmin or fibrinogen-scanning were compared with 1231 -rh-tPA-scanning. None of the other radioisotope scanning techniques was superious to ~23I-rh-tPA scanning. We conclude that InI-rh-tPA scanning could be a safe and rapid method for the determination of venous thrombosis. Highly purified human Fibrinogen was labelled with 1-123 using iodogene as oxidation agent. Radiochemical purity was always higher than 95 % and radioisotopic clottability was more than 90 %. After a single bolus injection into the superficial dorsal vein of the strangulated leg; planar scintigraphy of the leg, thigh and pelvis (3 regions) were performed immediately, with computer analysis of the 2,4 and 24 hours uptake. Following the 24 hrs imaging, routine three-phase RNV and CDS were carried out. The increase of 1-123-hFibrinogen uptake seems to be greater at 4 hrs image than at late image (24 hrs) in pts with anti coagulant therapy. In 32/126 regions of 21 pts positive findings were obtaineo in the 1-123-Fibrinogen uptake with good correlation of CDS results. 90 % of the lesions detected by 1-123-Fib, did not appear during RNV when Tc-99m-MAA was used. In case of the remaining 9 pts during RNV in 23/26 region as "hot spot" was considered. The RNV indicated the filling defect both in the acute and aged diseases well, but to estimate the proper extension of the fresh and aged thrombi the CDS seems to be superior. The aim of this study was to investigate, if the results of quantitative liver-spleen scintigraphy were representative of the functional long-term outcome in patients after spleen surgery. Overall, 59 patients (18 women, 41 men, age 18 -79 years) were studied 11 years (mean) after spleen surgery. 43 patients had splenectomy (11 of them with autologous replantation), and 16 had spleen-preserving surgery after injuries. Quantitative liver-spleen scintigraphy (planar anterior and posterior views) was performed 30 rain after i.v. injection of 185 MBq Tc-99m tin-colloid and splenic uptake (in % of the administered dose) and liver:spleen ratio were calculated. These values were compared with immunologic and hematologic parameters such as Howell-Jolly-bodies and pitted erythrocytes. The splenic uptake had a better correlation with the immunologic and hematologic parameters than the liver:spleen ratio. Patients after spleen-preserving surgery had according to a normal functional status of the spleen (as defined by normal immunologic and hematologic parameters) a splenic uptake of 3.0 +/-1.4, which is in the normal range. All of the 10 patients with replantation revealed splenic activity (with large interindividual scatter 0.8 +/-0.7 ). After splenctomy, no activity was seen in 18 cases, minimal splenosis in 15 (0.3 +/-0.3) corresponding to defects of the functional status. In conclusion, quantitative liver-spleen scintigraphy is a simple method for the assessment of the splenic functional status in the long-term follow-up of patients after spleen surgery. Clinical Centre of Nuclear Memicine and Radiotherap~ Medical Faculty, Sofia, Bulgaria It is known that in following up the erythrokinetics, an information aDout the localimation and the Oegree of eryth~ocytes J destruction is acquired. One disadvantage of the method is the long duration of the investigation. The purpose of the study was to work out a fast method for the erythrokinetics. We have investigated 41 Pie with haemolytlc anaemia, whose erythrecytes were labelled with SICr-aodium chromate / 4MBq / with determination of the difference in spleen to liver ratio / S/L ratio / between the thirm and the first day p.i. as well as S/L ratio at the end of the end of the investigation /between 12-14 may/. We have estimated that this difference was on the average 1,12 / above 1,0 in cases with aplenic destruction and below 1,0 in cases with liver destruction / end S/L ratio at the end of invest~gation-1,44 with very good correlation metwe~ them bath / r--~,94 /. In Pta with inmicstion for splanectomy / S/L ratio above 2--2,5 /, the difference between the third and the first ~ay was above 1,3. I~ could be concluded that, ~accerding to the proposed method, the localization and the degree of erythrocytes' destruction can be determined with high reliability, which speeds up taking decision aDeut eventual splenectomy. Bone disorders have been reported in Thalassaemia but the mechanism is conmplex and remains controversial. We studied B5 pts, 53 males and 47 females, affected by TM (81 cases) and T[ (14 eases), 69 of these (62TM,7TI) over 7yrs. At the f i r s t observation TM pts were divided into 3 groups by age: la(g-14 yrs:n.18), 2°(I5-18yrs: n.Bg), 3 ° (19-30 yrs:n.24); TI pts aged 20-42 yrs. TM pts were politransfused while TI had never received "blood transfusion; ¢2 age and sex matched controls were also studied. In all cases BMD (mg/cm2) by dual-photon absorptiometry in the distal radius was measured; serum PTH, osteocalcin (0), CT, la,25(OH)2D3 and CA and P ~ere also assayed. Both TM groups and TI pts showed significant lower BMD values compared to controls. BMD was lower in TI than Groups 3 TM. Mean Ca was significantly lower andP higher than cohtrols. PTH was within normal range but slightly elevated; hypoparathyroldism was found in 3 Group 3 TM pts. In 2 of these 0 was also low. Individual 0 levels were variable but on everage lower than in controls, only significantly for TI (4.57±I.2 VS 7.04±i.9 ng/ml). Mean la,25(OH)BD3 levels were lower in Thalassaemic pts than controls, slgnifioantiy only in Group 3 TM and TI (27.53±10.97 and 18.81+16.3 VS ~5.g¢ i 7.01 pg/ml). CT was normal in all cases. After 7 yrs all TM pts, who now belonged to Group 3, had a further signlflcant BND decrease in respect of controls as did TI. PTH levels decreased below normal range in 13 TM and I TI with mean values significantly lower than controls. There was a 4th hypoparathyroldism case in TM Group. Ca remained low and P high, slgnificantly. 0 and ia,25 (OB)2D3 ,ere confirmed low but significantly only in the latter. Low 25 (OB)D3 levels, assayed only at 2nd observation, were found both in TM and TI pts. Our data indicate low BMD in thalassaemla already in early age, further decreasing with disease progression. Both well known local factors and reduced active Vit.D netabolites synthesis, the latter inducing intestinal Ca absorption decrease and 0 production, may contribute to hone mineralization defeot. A progressive serum PTH decrement, presumably due to parathyroid hemosiderosis, may also play a role in advanced disease stages. Tc99m polyclonal immunglobulin (HIG) has been used to detect focal infection and inflammation. We performed a comparative study between Tc99m H/G and Tc99m MDP in the visualisation of inllammed joints in 20 patients with rheumatoid arthritis (RA) and variants of RA. Additionally, in order to show that immunospecific mechanisms are effective besides increased vascular permeability in the accumulation of Tc99m HIG , all the joints which accumulated this radiopharmaceutical were imaged with Tc99m human seam albumin( HSA). Tc99m HIG and Tc99m HSA scans were obtained at 2 , 4 and 24 hours after 5 mCi Tc99m HSA and 9 mCi Tc99m HIG. The quantitative analysis was carried out exclusively over joint regions. We conclude that 1-The detection of joint inflammation with HIG was significantly superior to the conventional bone scan with MDP. 2-The increasing Tc-99m H]G uptake between 4-24 hours in contrary to Tc-99m HSA, accentuates the role of immunospecific mechanism in RA. 12 patients (pts) with healing fractures (group I ), and 15 pts who t i l e d union of the fracture (group II ) were included in the study. All pts underwent planar static imaging 2 hr. after IV injection of 640 MBq Tc 99 m labelled citrate .With a 3 days interval, Tc 99 m-MDP bone seintigraphy was also pertbrrned.The findings of two seintigraphic studies were evaluated qualitatively and quantitatively by using R O I ' s drawn over tiacture ( L ) and conterlateral normal bone (c). It was noted 5 pts in group I showed positive Tc 99 m -MDP uptake but unexpectedly negative Tc 99 m-Citrate uptake. The mean L / C ratios of group I and group II were 1.4 Yr 0.13 and 2.20 ~-0.43 respectively (l~0.0005). In conclusion, citrate compound known to have a value in bone tbrmotion may be a promising agent in monitoring bone healing when labelled whith Tc 99 m. It was observed that Tc 99 m citrate images corralated with clinic and radiologic findings of bone repair better than Tc 99 m-MDP. Medical Faculty, National Oncological Institute, Hematologic Clinic, Orthopedic Clinic Bratislava, Slovak repubi. Radionuclide bone angiography or three phase bone scintigraphy was until now used mainly in diagnostics of primary bone tumors, inflammatory bone lesions and rarely for detection of the affliction of soft parts in bone tumors. In the present work we focused our interest of this procedure on an until now underestimated problem in the diagnosis of metastatic or systemic bone tumors with expressed s. c. osteoclasts activating factor / OAF /. In these the sino of enlarged osteogenesis is not always clear /cold lesions / and therefore the pathologic lesion i$ confirmed often only by a pathologically higher blood flow / f. e. plasmocytoma, lympboma, thyroid gland Ca, bypernephroma and so on /. For confirmation of this proposal we performed three phase scintigraphy in 1200 patients with above mentioned tumors. The most important group content 250 patients with plasmocytoma, in whom the investigation was performed for differential diagnosis, confirmation of diagnosis and follow up of therapy. In each patients with active plasmocytoma the blood flow was pathologically high, which decreased after sufficient therapy. Conclusion: In diagnosis of bone or bone marrow involvement in tumours with increased osteoclasts activating factor / OAF / the three phase scimtigraphy is an indispensable procedure, which increasses the sensitivity and specificity of bone scintigraphy. T.Hashimoto, J.Hashimoto, K.Nakamura, A.Kubo Department of Radiology School of Medicine Keie U n i v e r s i t y SCINTIGRAFHIC MEANINGS OF THE REFLEX SYMPATHETIC DYSTROPHY SYNDROME OF THE SHOULDER,HAND AND LOWER EXTREMITIES USING 3 PHASE BONE SCANNING. The aim of this s t u d y was to evaluate the meanings of 3 Phase Bone Scanning(3PBS)in Reflex Sympathetic D y s t r o p h y (RSD).3FBS was performed in 61 p a t i e n t s s u f f e r i n g from RSD of the s h o u l d e r , h a n d and lower extremifles.20mCi (740MBq)of Tc-99m MDP was administered i n t r a v e n o u s l y by bolus injection.Dynamic images were acquired simultaneously,10 minutes later early scan and 120 minutes l a t e r delayed scan were a c q u i r e d . From the point of the duration of the symptoms from the o n s e t , w e have divided the p a t ients into 3 stages.(0-2[},20-60,over 60 w e e k s ) I n RI angiog r a p h y h y p e r v a s e u l a r i t y was recognized in 13/20 cases (65 %)of s t a g e i p a t i e n t s , w h i l e 1/10(10%) and 1/5(20%) in s t a g e 2 and 3 r e s p e c t i v e l y . l n early scan hyperemia was recognized in 31/34 cases(91.2%)of stage i p a t i e n t s , 1 3 / 1 8 (72.2%)in stage 2 and 5/8(62.5%)in stage 3.In delayed scan h y p e r f i x a i i o n was recognized in 32/35 eases(91.4%) in stage 1,17/18(94.4%) and 5/8(62.5%) in stage 2 and 3 r e s p e c t i v e l y . But in 2 cases in s t a g e 1 and 2 , a l t h o u g h they have examined in s h o r t periods from the onset of symptoms,the ischemic c h a n g e s were seen in RI a n g i o g r ap h y , e a r l y and delayed scan. Their symptoms were r e s i s t ent for the p e r s i s t e n t t h e r a p y and showed the bad p r o g nosis. Therefore 3PBS may p r e d i c t the p r o g n o s i s as well as provide the useful information r e g a r d i n g the p a t h o p h y s i ological and clinical evaluation of RSD. From the literature the standard 3-phase scintigraphy of aseptic hip neerosis is known for rather high sensitivity, yet very low specificity and therefore also low reliability. Since we have been performing the modified examination 3T calculation and SPECT for some years~ we tried to find out in a retrospective study the amount of contribution of such modifies study to the reliability of examination. Material and methods:Our study involved 135pts with scintigraphye diagnosis of aseptic hip necrosis and 97pts without symptoms of aseptic necrosis. All pts underwent a 3-phase sointigraphy of hips with 3T calculation from the curve of first dynamic phase as well as SPECT of hips. In the patients with aseptic hip necrosis the process was verified. The calculated sensitivity amounts to 99.3%, specificity 98% and reliability 98.9%.By applying SPECT, we could exactly localize aseptic hip necrosis. Conclusion:The obtained results of quantitative analysis of relative perfusion in the artery phase (3T) evidence somewhat increased sensitivity, high specificity of examination which allows highly reliable diagnosis of aseptic hip necrosis. SPECT examination of hips performed in addition, however, allows exact localization of the process. F. Montravsr~ 1 , N. Younsi I , C. Rousseau I , S. Uzan 2, V. Izrael 3, J.N. Talbot 1 Services de M~decine Nucl~aire I, Glrnecolog ie2, Canc~rologie 3 . Hgpital Tenon, F75020 Paris, France The systematic prescription of a bone scan (BS) in the follow-up of patients (pts) with breast cancer is a traditional attitude which is now questioned. The aim of our study was to estimate the yield of this systematic BS, derived from one year experience. A BS (Tc-HMDP) was performed from nov 1992 to nov 1993 in 118 women (mean age : 59±12 yrs) with breast cancer. BS realized in the initial evaluation of the disease (reference document) and in the pts with known bone metastases were not included. In 74 asymptomatic pts, 28 BS were normal, 42 corresponded to a benign bone disease (BBD) and & were doubtful (M?). BS were motivated by bone pain and/or signs of disease progression (local recidive, increase of CA 15-3 or visceral metastases) in 44 pts. Seven BS were normal, 20 corresponded to BBD, 9 to metastases and 8 to M? (i with doubtful NMR and 7 with no further examination). These results show that no systematic BS led to the discovery of proven bone metastases. Further evaluation of the four doubtful cases is necessary before concluding if systematic BS in breast cancer follow-up is clinically useful (and able to allow early detection of bone metastases). On the opposite, proven bone metastases were discovered in 20% of the motivated BS. Bone seeking p h o s p h a t e s are known to localize in extraosseus sites such as the m y o c a r d i u m in m y o c a r d i a l i n f a r c t i o n . A p a t t e r n of diffuse myocardial uptake of 99m-Tc-Pyp and HDP (but not MDP) has also been noted in a p p a r e n t l y healthy patients. To assess the incidence of myocardial uptake in MDP bone scans and its r e l a t In-11 l-labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody cressreacts with myosin in skeletal muscle and has been used for detection of lesions in patients with rhabdomyolysis and polymyositis. We used this method on 7 patients with Becker type muscular dystrophy with a diagnosis based on DNA deletion and/or dystrophin staining. In 6 patients weak to moderate uptake of antimyosin antibody was detected in the calves and in some patients also in the thighs and upper extremities. In 6 patients with non-X-chromosomal dystrophy uptake was recorded in the calves and in 4 patients also in the upper extremities. In dystrophy patients MRI findings were usually more prominent in the thighs, whereas in the calves the antimyesin findings were relatively stronger. This discrepancy is probably due to the better preserved muscle bulk in the calves, showing pseudohypertrophy, whereas in the thighs muscle tissue has been replaced by fat and connective tissue. In Becker dystrophy the basic defect is an abnormal structure of dystrophin, a cytoskeletal protein providing membrane integrity, whereas in non-X-chromosomal dystrophies the basic defect is unknown. Our data indicate that in muscle dystrophies there is a defect in the sarcolemmal integrity. Of a total 24 major lesions in 9 patients with rhabdomyolysis lg could be suspected on clinical examination leavir~g 6 lesions localized only radioimmunodetection. The target-to-nontarget uptake ratios varied from 1.3 to 7.6. In 3 patients with polymyositis-dermatomyositis areas of both focal and diffuse uptake of antibody were observed. It is concluded that antimyosin scintigraphy can be used for detecting muscle lesions not only in acquired muscular diseases but also in hereditary muscular dystrophies, . In this study we describe our preliminary results comparing conventional bone scan (BS) and bone marrow scintigraphy (BMS) in detection of skeletal metastases in the follow up of breast cancer patients (pts). We have investigated eleven pts with histologically confirmed breast cancer. Whole-body scans and single planar scans were obtained 3-6 hours post injection of a single dose of 0,25 -0,50 mg murine MAb BW 250/183 (Behringwerke AG) labeled with 370-555 MBq of Tc-99m. Conventional BS using Tc-99m MDP and BMS were performed within an interval of 4 weeks. Some of BS and BMS lesions were confirmed by standard x-my procedures. BS showed bone metastases in 7 pts. BMS detected BM involvement in 8 pts, two of them with negative BS. In 6 pts with positive BS x-ray procedures confirmed osteotysis. One of these pts had negative BMS because the lesion was situated in the proximal part of the left ulna, which normally does not contain BM. Ten lesions shown on BMS were not present on BS. In l pt with multiple bone metastases a diffuse reduction of bone uptake on BMS associated with an intense liver and normal spleen uptake was observed. We conclude that BMS with antigranulocye MAb plays an important role in the detection of BM involvement in pts with breast cancer. BMS seems to have a comparable sensitivity to the BS and these two procedures could be complementary. In a previous study we demonstrated, that after administration of In-11 I-labeled human polyclonal non-specific immunoglobulin G (IgG) to rats with an infection In-111 is retained in the inflammatory focus, whereas IgG is washed out at decreasing plasma concentrations. In order to further elucidate the role of the bifunctional chelating agent DTPA, we studied the behavior of In-111-C-14-DTPA-IgG-1-123 in rats with a focal infection. C-14-DTPA-conjugated IgG was labeled with In-111 via citrate transchelation. In-l11-C-14-DTPA-IgG was labeled with 1-123 according to the BoRon-Hunter procedure. Labeled IgG was purified by gel filtration. HPLC was performed as quality control. Young Wistar rats with a Staph. Aur. infection of the left calf muscle were i.v. injected with 0.2 ml of a solution containing 0.45 MBq In-111, 50 KBq C-14, and 1.8 MBq 1-123 labeled to 2.5 mg IgG. Rats were sacrificed at 2, 6, 24, arid 48 hr. p.i.. Activity uptake was determined for plasma, urine, abscess, and various other tissues. Averages + SD were calculated for groups of five rats. Plasma and urine samples were analyzed by HPLC. The radiochemical purity of the IgG-preparation was > 95%. The DTPA:IgG ratio was 3:1. In all tissues tested, except for the lung, the uptake of both In-111 and C-14-DTPA was much higher than the 1-123-1gG uptake (48 hr p.i., liver: In-ll 1: 1.1+0.1; DTPA: 1.0+0.1; IgG: 0.35+0.03; abscess: In-111: 1.1+0.1; DTPA: 1.7+0.2; IgG: 0.7+0.1 (%ID/g+SD)). The abscess uptake of C-14-DTPA was significantly higher than that of In-111 (p<0.01). The 1-123 data were similar to the C-14-1gG data from a previous experiment in the same model. In plasma release of In-111 from IgG was observed over time, whereas DTPA remained conjugated to IgG. A small amount of In-111 in plasma was found to be transchelated to a substance with a molecular weight slightly smaller than that of IgG. Both In-111 and DTPA appear to dissociate from IgG. In abscesses the DTPA uptake is significantly higher than the In-111 uptake. The aim of our study was to investigate the value of 99m-Tc-anti-NCA 95 monoclonal AgAb scintigraphy in patients suffering from FUO. Forty-five patients -24 females and 21 males (age 1-76 years) -were examined by planar wholebody images 4 and 24 hours after i.v. injection of 185-555 MBq of 99m-Tc-AgAb. In 24 patients SPECT was additionally performed after 24 hours. The final diagnosis was established by histology, blood cultures, routine laboratory methods, and radiology including MRI. Fifty percent of the patients had infectious, 14 % autoimmune, I0 % malignant, and 15 % other diseases. In Ii % the etiology of the fever remained unknown. A total of 16 true positive infectious foci was found (only hot spots were considered), 5 skeletal, 5 abdominal, 2 thoracic, 2 cranial, and 2 in other locations. Three false positive findings originated from necrotising colitis, uremic colitis, and a mediastinal mixed tumour. There were 9 false negative foci in patients with endocarditis, pneumonia, abdominal abscess, and osteomyelitis of the central skeleton. Sensitivity and specificity of the AgAb scintigraphy regarding infectious disease (prevalence 44 %) amounted to 64 % and 89 %, respectively, positive and negative predictive values were 84 % and 70 %, respectively. In conclusion, AgAb scintigraphy is an important diagnostic tool in proving or excluding an infectious etiology of FUO. Radiolaballed polyclonal human immunoglobulin G (HIG) has been recognized as a reliable modality for localization of infection and inflammation. The aim of this study was to evaluate if scintigraphic uptake has a relationship with clinical and biological parameters of inflammation thus allowing the measurement of the degree of synovitis. Twenty four patients with rheumatoid arthritis and active synovitis (7 males 17 females, mean age: 54+ 11 years) were studied. Scintigraphy with 99mTc-HIG (740 MBq) was performed at 4 hours p.i. The number of painful and swollen joints, the Thompson index for clinical activity and the scintigraphicuptake by a quantitative analysis were evaluated. Sedimentation rate, C-reactive protein (CRP), hemoglobin, baptoglobin and serum levels of IL-2, IL-6 and c~TNF were taken as biological parameters of inflammation. In 8 cases serum samples radiactivity at 10 min and 4 hours and synovial fluid radiactivity at 4 hours were evaluated. Protein bound activity was measured by Sephadex G-25 (PD-10 columns) chromatography. Radiochemical purity was > 99% in all labellings. Radioactivity in synovial fluid was 22.8_+10.6% respect to plasmatic activity/ml and it represented only 0.05+0.04% of the total injected dose. Protein bound radiactivity in plasma and synovial fluid was higher than 95%. Scans showed that 91% of swollen and 94% of painful and swollen joints had pathological uptake. Quantitative analysis of scans demostrated that the sum of scintigraphic uptake in pathologic joints correlated significantly with the number of painful joints (r =0.46), the number of swollen joints (r=0.57), the Thompson index (r=0.59), the sedimentation rate (r=0.55), CRP (r=0.59) and hemoglobin (r=0.49). We can conclude that scintigraphy with 99mTc-HIG is a reliable method to detect active synovitis and to evaluate the degree of inflammation. Early diagnosis of osteomyelitis and follow up in infection treatment in oro-maxillo-facial sugery is quite important. In our study we comprehended the behaviour of anti-Granulocyte AB in 35 patients with osteomylitis in the oro-maxillo-region with Tc99m-labelled nanocolloids ( n = 25 ). 35 patients with a suspected infection or osteomywlitis in the head and neck region were investigated with the 123-NCA-MAB (Behring) labelled with 800-1200 MBq Tc-99m. Analog and SPECT images 4 and 24 hrs. after injection were obtained. In 25 patients additional bolus injection of 740 Mbq Tc99m-labelled nanocolloids with aquisition of analog and digital sequences were done. The results were correlated to anti-granulocytesantibody-uptake, sonography, CT and MRT. The scintigraphy with nanocolloids is a proven method in detecting chronic septic processes. In acute cases with wound trauma enlarged nanocolloid uptake was seen in the surrounding bone tissue due to the unspecific inflammation, so that infection cannot be exactly localized and differentiated to early postoperative alterations. In these cases the anti-granulocyte-soan showed in the planar and SPECT images a high concentration of antigranulocyte-AB so that localization and identification of the infection even in the SPECT-slices was better than in the nanocolloid scans. Gallium-67 has been replaced by the labelling of leukocytes with either I n -l l l oxine or Tc-99m HMPAO for the detection of inflammatory processes. White blood cells (WBCs) play a major role in the body defense mechanism, and are activated at the onset of infection to immobilize, phagocytize and subsequently destroy the causative bacterial agent. Most of the patients scanned with Tc-99m HMPAO WBCs are, by virtue of their patho-physiology, on various regimens of drugs. We have chosen a number of pharmaceuticals to evaluate their impact on the labelling efficiency (LE) of WBCs. Drugs do not only affect the morphology of the WBCs, but can have deleterious affects on the chemicals used in the labelling process (e.g. penicillin G in high concentration inhibits hetastarch's effect). Edrophonium, Azathioprine, Dipyridamole, Enalapril, lsoproteronol, Penicillin G, Co-trimoxazole, Streptokinase, Diazepam, Cefazolin, Cyclosporin, Anti-human Lymphocyte IgG, and Adriamycin were investigated. Most of these did not effect the LE of WBC's (even in high plasma doses), which showed a slight potentiation with Co-trimoxazote and Dipyridamole, and a 75% reduction in the presence of 0.83 mg/ml Anti-human Lymphocyte IgG. From a retrospective study we conducted, it is not clear whether the leukocyte cotmt had any affect on LE. However, our results emphasize the need to screen the patients' drug regimen before embarking on a WBC-labelling test. Nine postoperative patients without clinical symptoms of infection were also studied. LS was carried out with mixed, autologous leukocytes, labeled with 99mTc-HM-PAO in vitro. CT scans were obtained through the use of intravenous contrast material in the usual way. Signs in the LS of control patients were as follows: activity irregularity, biffed sternum and diffuse, increased lung uptake of leukocytes. CT scans of the control group showed focal edema, focal hematoma and moderate sternal abnormalities. In one control patient the CT proved positive. In 11 cases with clinically verified infection 9 proved positive on LS and 8 on CT. LS was positive in cases with either a superficial or a deep process. CT determined in all cases, whether the infection was limited to the presternal space or wether the sternum and mediastinum were also involved. In 2 cases with a negative clinical picture, both CT and LS proved negative. Conclusion: Specific signs of infection can differentiate from the symptoms due to sternotomy when LS is used, but overlapping of the symptoms was revealed by CT. LS and CT are sensitive methods for the early detection of postoperative sternal wound infection. CT is superior for the exact localization of the process. A combination of LS and CT is suggested in the diagnosis of poststernotomy infection. Sc{ntigraphy with 99mTC-HMPAO-leukocytcs detection a non invasivo method for infection has shown great for cerebral abscess diagnosis. We studied 28 patients with leukocytes MBq di 99mTC-HM:PAO) because of the suspldon of cerebral abscess. Scans were performed at 1,3 and 24 hours after the h:d'ection of labeledin leukocytvs, of 18 patients with positive TC, 7 had positive scbatigrams. Neumsu~gical (3), clinical (3) and authephtic control cen_6.rmed the presence of abseea in all of them. The other patients with positive TC (11) had negative scan and in all cases it was demonstrated noninfective pathology (neoplasm -lesion, MM, ematoma). Of 10 patients with negative TC, 2 had positive scintigmms confirmed by surgical control. Padant with negative TC and leuk. scan (n8) conclusive diagnosis (4 surgically and 4 clinically) of nan -infective pathology. In this study sensitivity andspecificity were 100%. Even this study result is probably mleted to ac,¢umte patients selection, we think that leukocyte scan plays a centrakole in abscess diagnosis, particularly in the early stage when neuroradiologic interventhon is more efficient. provided a complete and satisfactc~y aocuracf. ~ aim of this study was to u~L[~ire the reliability of WBCs and CTs in detectir~ l~I. 22 pts. with s~pected ~ were studied. CTs andWBCs wereperfcm~d in all cases. Pts. ware categorized into three gmx~s auu~ding to the clinical linings. Gr~x~ A included pts %t,o had ~T~fic sigrs of graft infectian. In group B pts had ~ific of graft infectian . Croup C inca,~ pts. ~ho had anaston*Mmic aneurysms variably associated with rmnsl=ezlfic sigrs of PVGI . Ehe final d~is was made cn the basis of the ~t i v e f'u,limgs, culture results or 18-month follc~,~-qo in pts. who did not tmdergo surgical exploration. ~ results are .ahown in the follcm~ig table: n TP ~N FP FNITP EN FP FN I Grotto A 3 I 0 0 2 3 0 0 0 G~x~B 8 3 3 0 2 5 3 lhallitm-201 imam_rig has been widely used to differentiate posttherapy reactions from residuel viable tuner, local r~urrones or fibrosis. But the ability of 201-TI to discriminate posttherapy changes superimposed with infection/inflmmation is ~elear. In this experimental study, it was aimed to investigate the role of 201-T1 in localization of infected/iaflmmed tissues. 24 rats infected with Staphylococcus sereus inoanulation and lO rats injected with a standart volume of saline solution (SS) into thigh nmsele were studied. 24 mad 48 hours after micrcorganisns and SS ac~5~lstration, 18 ~q 201-Ti was applied intravenously. 20 rain. and 3 hr. planar images were r~orded. The observed hyperactivity was evsiuated qualitatively and quantitatively csiculating the ratios derived fran ROI's drawn over lesion and contrlateral thigh muscle (L/C). After imaging procedure, histopatbelogical and microbiological material was obteined. While control group showed no abnormal activity accmmlation, infected rats demonstrated marked hyperactivity especially on 20 rain. images. Mean L/C ration of 20 rain. and 3 hr. images of infected rats were 2.18 • 0.20 and 1.52 ~ 0.04 respectively (p 0 ° was significantly different among the groups "normal" (17/61 = 28%), "latent PH" (35/60 = 57%), and "manifest PH" (11/19 = 58%). This resulted in a sensitivity of the angle analysis of 57 % and a specificity of 72 % for the detection/exclusion of PH, Focal dyskinesias were found in 10/19 patients with manifest PH yielding a sensitivity of 53% and specificity of 78% for the detection/exclusion of manifest PH. In conclusion, the phase analysis in patients with nonspecific pulmonary disease gives informations on the detection/exclusion of PH under rest conditions, which are available only by various exercise tests. In order to show the effect of increased lung uptake of Tc99m HMPAO on the brain uptake in smokers, posterior thorax, h e a d a n d a n t e r i o r a b d o m i n a l images of 16 patients(10 women,6 m e n , m e a n age 44+8, with stroke, psychiatric disorders and migraine who were referred for brain SPECT) were obtained 30 minutes after injection. There were 9 smokers(S) and 7 nonsmokers(NS). S c o n s u m e d 20_+7 cigarettes/day. 6 smokers s m o k e d 3-4 h o u r s j u s t before injection (RS). Cigarette c o n s u m p t i o n of RS was not different than S(22_+7 cigarettes/day). Regions of interest were placed on the lungs, liver, s p l e e n , b r a i n a n d b a c k g r o u n d ((bckg), midllne between the lungs). Average c o u n t s per pixel were u s e d to calculate Lung/Liver (LL), L u n g / S p l e e n (LS), Lung/Bckg(LB), Brain/Bck(BB) a n d Left/Right lung(LR) ratios. LL, LS and LB were significantly higher in S t h a n NS (.01 ;SF~ = 29.8 ml/min). The usefulness of the IR.F. was observed in 2 transplanted patients with unexpected very high plasma clearance determinations ( 268 and 301 ml/min) suggesting technical problems as extravasation of injected activity or wrong dilutions. Corresponding I.R.F. values gave a very good agreement between predicted and experimental clearance values, eliminating the possibility of such mistakes. This method using only scintigraphie data does not depend on plasma counting and is especially useful when an accurate clearance measurement cannot be obtained due to a technical failure. ~D.Hui~, 2B.Br~ia~i~, 3V.Mrzljak,~D.Gro~v, tM.Poropat, ~D.Dodig, ~S.Kusa~id-Kuna ~University Hospital Center "Rebro", ~University Hospital "Merkur", 3Institute for Diabetes "Vuk Vrhovac", Zagreb, Croatia We performed 99mTc-DTPA renal scintigraphy and ultrasound Doppler examination in 21 patients (14 woman, 7 man, mean age 35, 42 kidneys) with long term diabetes mellitus duration (mean 19 years). Renal blood flow expressed as a percentage of cardiac output (RBF) and glomerular filtration rate (GFR -4 blood samples), computed for each kidney, were compared with the Doppler ratio of peak diastolic to systolic velocity (D/S), serum creatinine level (SCL) and creatinine clearance (C CR). Obtained correlations are presented in The results showed poor correlations among D/S and other indicators of renal function, which could be probably improved with more precise instruments. The radionuclide values, obtained from single injection of DTPA, correlated well with SCL and C CR values. SCL seems to be more reliable indicator of glomerular filtration rate in diabetic nephropathy than C CR, which is greatly dependent upon accurate urine collection. Kairemo KJA, Taari K, Salo JO, Rannikko S, Kivisaari A Deparments of Clinical Chemistry, Urology &Radioiogy, Helsinki University Central Hospital, FINLAND Twelve partial nephrectomies (NE) were performed in 12 piglets (11-17 kgs) using either Nd-YAG laser or steel scalpel. Total NE was performed on the left side and partial NEs on the right side ( lower third of the kidney) with both techniques. Renal function was studied with TC-99m-DTPA renography, serum urea and creatinine levels preoperatively,and 1 and 2 weeks postoperatively. The piglets were imaged in each session for 30 min by collecting 10-sac frames from PA view of an anesthesized anima]~ The injected activity was 37 MBq. Serial blood samples were taken from the subclavian vein at 0,i,2, 3, 5, 15, 25, 40, 60 and 120 min (6 animals) after Tc-99m-DTPA injection. The DTPA dissappearance rate (DDR) was determined from these samples and in other cases a blood sample at 20 min was used. The DDR was also determined from the dynamic gamma imaging data: ROI regions upper body, spleen, heart, and kidneys. The ROI analysis correlated well with the blood sampling data ( r=0.97~ p< 0.00i). The reference values for piglet DDRs were in laser group ( T e c h n e t i u m Hag3 C l e a r a n c e is p r o p o r t i o n a l to OIH C l e a r a n c e in adults and can be e s t i m a t e d u s i n g a single sample t e c h n i q u e similar to the m e t h o d d e s c r i b e d by T a u x e and Co-workers. The r e l a t i o n s h i p b e t w e e n c l e a r a n c e a n d age and g e n d e r has not been reported. We p The aim of the study was to estimate possible risk factors in developing diabetic nephropathy in patients with IDDM.The study consisted of 114 patients 63M,51F.~= 12,5 years SD=2,9.Blood pressure was normal and their usual parameters for renal function (plasma ccreatinine urea) Cr,Ur, were normal.Depending on the poor,moderate or sufficient metabolic control(HbAlc)the patients were divided into 2 groups. GI. HbAlc The following parameters were measured,l)PRA by RIA method 2) urine albumine. 3)HbAlc 4)GFR Cr-51 EDTA.The linear regression analysis was used for A.B.C and t test between GI,G2, D and all diabetics.There was very goO~ correlation for Alb.a~ 368, Alb.and GFR r=O, LS in g~'oup B; 49 in group C. PRA in gi'oup L was lower significantly tha~ in group 2. GFR did not differ signifih~itly between the 2 groups.Moreover control group D was higher significantly _than in diabetics. Conclusions !)The low levels of PRA in patients with poor metabolic control is one more risk factor of developing diabetic nePhropathy. 2)PRA in control group is higher than in young diabetic patients with IDDM. 3 Aim of this intraindividual comparative parallel study was to evaluate the correlation of different parameters between 1-131 hippuran and Tc-99m MAG 3. 52 patients (essential hypertension, 12; renal artery stenosis, 5; interstitial disease, 21; tumor, 4; obstruction, 10) aged between 22 and 65 years were studied after appropriate hydration using-18 MBq 1-131 hippuran (Oberhausen 4-probe device) and, within 4 hr, 185 MBq Tc-99m MAG 3 (gamma camera, ROI technique). Overall, there was a good correlation for the split function of the kidneys for the two tracers (r = 0.80) while the time-to-peak (tma x) and the half-life of the tma x gave low correlation values (r = 0.56 and r = 0.55, respectively). Time-to-peak was 3.54 +/-1.71 min for hippuran (versus 3.56 +/-1.48 for MAG 3) and half-life was 6.4 +/-2.74 (MAG3:8.9 +/-3.68) with more significant differences in patients with interstitial disease and tumors. We conclude that split function has a good correlation between hippuran and MAG 3 while careful comparison for other parameters from time-activity curves is recommended. MJauch 1, P.Benz 1, F.Fomardi 2, J.Spitz 1, E.Oberhausen 3 1RNS PET-Zentrum Wiesbaden, 2 Parkinson Fachklinik Bad Nauheim ,3Universit~it d.Saarlandes, Abtf.Nuklearmedizin The therapie of Parkinson's disease and diseases similar to Parkinson's has improved a lot within the last years. Using the various therapie modalities requires a differentiation between the subtypes of Parkinson syndrom. Out of 192 patients with Parkinson syndrom, provided with FDG-PET, a group of 70 patients with "Parkinson plus" disease was selected and compared with 23 patients with Parkinson's plus dementia and 17 patients with MSA respectively. All patients had a neurological examination ( by the Parkinson Fachklinik). PET: After overnight fasting and a relaxation phase (15 rain.prior to injection) 200 -350 MBq 18 -FDG were injected. Acqusition was performed on a GEMS 4096 system using a standard protocol:three emission scans (10 rain. each) 30 -60 rain p.i. were acquired. For quantification the autoradiographic method (Phelps/Huang) or samiquantitative ROI technique (ratios) was u Patients with "Parkinson's plus" disease showed a moderate reduction of glucose metabolism in frontal cortex and a more severe reduction in parietal and occipital cortex. Within the basal ganglia the reduction of glucose metabolism was more moderate compared to the cortex (in 60% the caudate nucleous showed a reduction, in 30% the putamen and in 10% the thalamus). Patients with Parkinson's disease plus dementia had a reduced uptake in general, especially in the parietal and occipital cortex but nearly no disturbance of glucose metabolism in the basal ganglia. 40% of MSA patients had a moderate reduced uptake in frontal cortex, nearly no reduction in parietal and occipital cortex but a severe dropdown (in 60%) in the putarnen There is evidence for the possibility of discrimination between the three subgroups by measuring cerebral glucose metabolis therefore it is a usefull tool for group related therapy. We tried to predict the capacity" of recovery of patients suffering from acute ischemic attack, by testing the relation to the amplitude of the vascular reserve. Nine volunteers and 36.patients (26 strokes, 10 TIA) were included in the study. Each of them was first injected with 300 MBq of Tc-HM-PAO and a tomography with a 3-head camera was performed 5 minutes later, 30 steps of 4 ° per head,75 sec per step, in matrix 128x128. Twenty minutes before the completion, 1 g acetazolamide (10 ec saline in case of volunteers) was injected. At the end of the study, 520 MBq of Te-HM-PAO were again injected and 5 minutes later, a second tomography was obtained, using the same parameters as for the first, but 42 seconds per step. Automatic analysis included 3D geometric correction (necessary despite a dedicated brain holder), activity correction (difference in dose, acquisition time, ...), automatic detection of the pathological regions (based on flow and response to acetazolamide) and determination in the region of the area, the mean and the maximal value of the flow and the response to aeetazolamide. The follow-up of the stroke patients was pursued during at least 1 month and only medical treatment was applied. Significant correlation (p=0.01 ) was found between the area of low flownormal response and the hypo density seen on the CT-scan on the 4th day after the attack. Significant correlation were also found between the clinical outcome and the defined regions, specially (p=0.001) between the zone of normal flowabnormal response and the clinical outcome during the first 2 weeks. In conclusion, the acetazolamide test combined with a full automatic software alhiws a good prediction of the clinical outcome of stroke patients, which looks particularly interesting for the evaluation of the therapeutic effect of drugs. Controlled hyperventilation is supposed to be an adequate therapy in cerebral trauma patients and is often combined with intravenous administration of anaesthetics. In order to test this clinical procedure cerebral blood flow (CBF) and regional glucose utilization (MRGlc) was assessed in 27 ICU patients with dynamic positron emission tomography (PET). The peffusion measurements were performed with [15-O]-H20 using a SIEMENS/ECAT 951 scanner. Perfusion was determined under baseline conditions (hypervenfilation / analgo-sedation) and after an additional narcotic dose. In the next step perfusion was measured under normoventilation (CO2et = 5.5%). Finally, MRGlc was determined under newly adjusted baseline conditions using [18-F]-Fluoro-Deoxyglucose. Under baseline conditions the mean perfusion was 0.42 mI/min/ml. After additonal narcotics application mean peffusion decreased to 0.33 ml/min/ml (-21%) but maximum reduction amounted to 48%. During normoventilation a mean increase in peffusion of 34% above baseline was observed. MRGlc under baseline conditions was significantly reduced as compared to normal values with a mean of 0.15 I.tmol/min/ml. Although the mean decrease of peffusion under hyperventilation in combination with anaesthetics is tolerable, critical values in some patients occured. Therefore, the concept of hyperventilafion in the manegment of head injuries appears to be questionable. Obviously, the additional application of intraveneous narcotics can be dangerous. 2)Dept. of Neurology, University of Bonn, FRG. The aim of this study was to compare the validity of regional glucose consumption (rCMRglc) and regional cerebral blood flow measurements (rCBF) in the diagnosis of probable Aizheimer's disease (AD). Diagnosis of probable AD was established using NINCDS-ARDRA criteria. Ten normal volunteers and sixteen patients with probable AD were studied with both modalities within one day. Regional CMRglc was measured using FDG with the PET-camera PC-4096; brain perfusion was determined using HMPAO and a triple-detector camera. The images were visually evaluated for zones of reduced rCMRglc and HMPAO uptake by three independent observers. The results are summarised in Table 1 . The data indicate that even with a state-ofthe-art SPECT technique sensitivity in diagnosis of probable Alzheimer's disease is higher using measurements of glucose metabolism when compared to perfusion. rCBF CHANGES IN EPILEPSY USING 99mTc-ECD: A QUANTITATIVE APPROACH Regional cerebral blood flow (rCBF) studies play an important role in the presurgical evaluation of patients with epilepsy. In the localization of epileptic foci the highest efficacy has been described for the combination of ictal and interictal studies. The application of the new rCBF tracer 99mTc-ECD in this indication is still under evaluation. The aim of present study was the quantitative evaluation of 99mTc-ECD uptake changes in ictal and interictal phases of focal epilepsy. In 8 patients ictal and interictal rCBF SPECT studies using 99mTc-ECD with a high resolution SPECT system (CERASPECT) were performed. In 5 patients the ictal SPECT study was done twice (41_+8 rain delay) to measure the tracer washout from hyperperfused areas. The SPECT data were analysed by a standard automatic quantification method, in 10 cantomeatal (4 under, 6 over the thalamus; 24 ROIs/ 1 ring /slice) and in 4 (under the thalamus, 2 x 24 ROIs/2 rings/slice) horizontal orinted transversal slices. Corresponding to the visual evaluation the quantitative analysis showed a significantly increased tracer uptake at the epileptic focus in the ictal study compared to the interictal study (asymmetry index: 1.23_+0.08 and 0,88-+0.03 respectively). In patients with repeated SPECT studies the washout from the hyperperfused areas was lower than from the total brain (8.9-+2.3% and 13.5-+1.6% respectively p<0.01). Compared to cortical areas the difference was statistically not significant. We concluded: 1. 99mTc-ECD SPECT is able to detect rCBF changes between ictal and interictal stages in epilepsy. 2. There is no loss of contrast (focus / other brain region) to be expected with time elapsed in the ictal study. The aim of this study was to evaluate relations between regional cerebral blood flow and neuropsychological disorders resulting from rupture of aneurysms of the anterior communicating artery. Blood flow was analysed in 22 patients at least 3 weeks after surgery using SPECT method, rCBF values were calculated in i0 regions of interest on each side of the brain. Attention, orientation, executive functions, short-term and long-term learning (verbal, visuo-spatial) , semantic memory, retrograde episodic memory, general cognitive performances were investigated. Flow drop was observed in the 3 frontal ROI, predominating on the right side. Stepwise variable selection (p=0.05) shown that (1) right frontal and cingulate flow values entered in the best predictive model of attention disorders; but right posterior flow had inverse action on same variables, i.e. high flow was associated with longer reaction time and lower performances on go no-go test (2) right or left frontal reBF entered in the predictive models of orientation and amnesia, (3) frontal CBF explained performances in the Wisconsin Card Sorting Test, but had adverse effects on performances in the London Tower Test evaluating planning. Frontal rCBF drop may explain most of the cognitive consequences of frontal medio-basal lesions, with clear association between right frontal cortex rCBF and attention and non lateralized effects on memory. But posterior rCBF increase previously reported (Rousseaux et al., 1994, Stroke) could also have adverse effects on attention. Based on limited work with PET that stated visual stimulation of one eye activates contrlateral temporal and frontal cortex, 10 patients (4 women, 6 men, age range 21~-37) with strabismic amblyopia (4 left, 6 right eye) were imaged. If the vision of the amblyoplc eye is supressed and the sound eye is used to generate image in amblyopic patients, stimulation of contrlateral cortex of the sound eye should be observed when both eyes are open. Brain SPECT with single dedector rotating gamma camera (GE XR/T) was performed twice with the administration of 555 MBq Tc 99m HMPAO, one in basal conditions and the other following visual activation by staring at a blue spot on a pink background for 6 minutes. 2 pixel slices parallel to the orbltomeatal line were reconstructed using Butterworth filter. Activation of the brain regions were evaluated visually. In all patients, primary visual cortex (PVC) showed increased uptake after stimulation. 6 of the patients showed temporal and 5 of the patients showed frontal activation contrlateral to the sound eye. This study suggested that amblyopic model is not the same with the one eye closed model.When two eyes are open, more complex mechanisms may be involved. And there may be the contribution of the amblyopic eye in temporal and frontal cortical stimulation, though its' Image is not fused with the image of the sound eye in PVC. In patients with Systemic Lupus Erithematosus (SLE) cerebrovascular involvement can be present up to 75% of cases. To evaluate the relation between perfusion defects and the presence of anticardiolipin antibodies and lupic anticoagulant factor we have studied 14 SLE patients (13F, 1M mean age 32.4 years) with a disease duration ranging among 3.5-6.4 years. A brain perfusion SPET scan was performed after i.v. administration in resting conditions of 740 MBq of 99mTc-HMPAO using a dedicated device (CERASPECT, DSI, USA). SPET studies were acquired for 30 minutes and the images reconstructed using a Butterworth 2D filter and corrected for attenuation using Chang's method. The semiquantitative analysis (ratio between cerebral region/cerebellum) was performed on 10 transaxial slices 9.6 mm thick and the results were compared with those obtained from normal subjects sex and age matched. Cerebral perfusion abnormalities were observed in 9 patients (64%), mainly in the frontotemporal region, in one or both hemispheres. The lupic anticoagulant factor was positive in 3 patients (21%), alt with an history of multiple trombophlebitis and peripheral arteropathy: the corresponding SPET images were normal in 2 cases while in the third a perfusiori defect was evident in the right temporal region. Of the 5 patients (35%) positive for anticardiolipin IgM antibodies, only 2 had perfusion defects, both in the fronto-temporal regions. Eight patients (57%) had positive IgG: their SPET scans were normal in 3 cases, while perfusion defects were present in the other 5. In 4 patients (28%) both the antibodies were present and in one the lupic anticoagulant factor was also positive. The corresponding SPET studies were positive only in two cases. Our data confirm the involvement of the cerebral circulation in the SLE patients and the capability of brain perfuion SPET scans to detect them, while reduced cerebral perfusion does not seem to be correlated to the presence of antibodies, well-known risk factors for thrombosis. N. G6k~ora, T Atasever, K G~c~yener, G Vural, N. l l g l n Gazi University Medical School D e p a r t s o~ Nuclear Medicine and Neurology Ankara-T0rkiye Down's syndrome(DS) is characterized by moderate mental retardation and a variety of abnormalities involving multiple organ systems. There is a high incidence of Alzheimer's disease(AD) type dementia beyond age 35. Tc-99m HMPAO SPET brain perfusion imaging of 12 DS patients(age range 3 to 24 years) were performed and these images were compared to a greup cf i0 age matched controls inorder to define brain perfusion patterns in different ages and its reIation to AD type hypoperfusion pattern. SPET scans were acquired 15 minutes after i.v.injecticn of 185-555 MBq of Tc-HMPAO using a single head rotating gamma camera.Scans were interpreted both visually and quantitatively by drawing multiple mirrored regions on the cerebral hemispheres. A side to side asymmetry exceeding 10% between the mirrored regions were accepted to be abnormal.5 DS cases demonstrated normal brain perfusion, 3 cases showed frontal hypoperfusion, other 4 cases revealed right or left parietotemporooccipital (PTO) hypoperfusion with or without frontal hypofrontality, Briefly 7 out of 12 young DS cases without dementia symptoms revealed mostly frontal and/or PTO hypoperfusion. These findings suggest that DS subjects without dementia symptoms may show abnormal brain perfusion. Brain perfusion imaging in younger DS cases wi]l be useful in identifying baseline perfnsion state and may help to predict dementia earlier and in the assessment of the prognosis of the patients. The present study is part of a comparison between non-diabetic and IDDM subjects with respect to the brain energy metabolism. The regional uptake of ketone bodies in the human brain was investigated in four healthy, fasting volunteers. The regional time course of the tracer in the brain was measured by positron emission tomography (Scanditronix PC 2048-15B) during i0 min following a bolus injection of 400 MBq [l-llC]-~-hydroxybutyrate. The time course of the tracer in the arterial plasma was also measured. The plasma concentration of ~-hydroxybutyrate was 20 -90 pmol/ml. A three compartment model with three rate constants and blood volume as parameters was applied. No correction for possible losses of tracer was made. The average influx rate constant for ketone bodies into the brain was = 0.03 ml/g/min, i.e. about one third of the corresponding value for glucose. This estimate is comparatively insensitive to possible tracer losses (IIC-CO2) from the tissue. The uptake was largest in grey matter. The average distribution volume of ketone bodies was = 0.005 ml/g, indicating a very low concentration of ketone bodies in the brain, and about 1/20 of the corresponding value for glucose. Any correction for tracer losses tends to lower this estimate. The results show the feasibility of determining transport kinetics of ketone bodies with PET. Krolicki L, Mikolajkow A, Trabka T, Bacia T, Graban W. Dep. of Nuclear Medicine, Medical School of Warsaw. The aim of this study was to evaluate CBF-SPECT study before,during and 3-4 days after Ketamine or Brietal activated epileptic discharges. CT,MRI and conventional EEG examinations were non diagnostic in all cases. 99mTc-HM-PAO as a blood flow tracer and gamma camera Orbiter 75 were used. K e t a m i n e study: f r o m 30 patients which were examined i0 were normal in first examination,but showed regional decrease of the blood flow during (n=6) or after Ketamine stimulation (n=8). Only in one case all examinations were non-diagnostic.Remaining group showed more pronounced signs after Ketamine stimulation. Brietal study: Ii patients were examined.Only during Brietal stimulation focus of decreased CBF were observed in two cases. In 9 cases Brietal did not changed the pattern of blood flow disturbances. In conclusion: pharmacological activation improved the sensitivity of the CBF-SPECT study in defining the focus of epileptical discharges which showed a diminished radiotracer uptake.Ketamine activation seems to be more promising method in those cases. Shulda d a. Nucl Med Sect, Areteion Univ Hosp, b. Nucl Med Dept, Med Coll Wisconsin, Milwaukee, c. Athens School of Medlcine, Athens, d. CNR + Nucl Med Dept St Eugenio Hosp, Rome EMBRYONIC NEURAL CELL ADHESION MOLECULE (eNCAM) AND NEURON SPECIFIC ENOLASE (NSE): NEW PROGNOSTIC MARKERS FOR BRAIN DAMAGES NSE is synthesized in high concentrations in the astrocytes and Schwann' cells. eNCAM is one of the various isoforms of the intercellular adhesion molecule, normally involved in neuron-neuron cell recognition. As a matter of fact, every structural damage of the brain tissue should lead to a leakage of these substances both into the eerebrospinal fluid (CSF) and blood serum (BS); consequently both could be considered as suitable CSF and BS markers for cerebral tissue damage. The purpose of this study was to evaluate the clinical usefulness of eNCAM vs NSE in patients (pts) with isehemie stroke (IS). Sequential samples of CSF and BS were taken from 56 pts (28 males aged 68 to 80 yrs) and 28 females (aged 64 to 76 yrs) with the diagnosis of IS, within 48 hrs and at 8,16 and 24 days after onset of the disease. NSE de-terminations were assayed with a solid phase IRMA (BYK-Sangtec-Diagnostica Germany) while eNCAM was measured with a solid phase RIA (Behringwerke AG). c r scanswere performed for correlation with the lesion size. Based on our results, we can conclude: a) CFS and BS concentrations of eNCAM and NSE reflect (i) the severity of the disease (IS) and (ii) the extent of brain damage, b) BS and CSF levels corrclate while c) repeated measurements can be used as prognostic tool of the ischcmic brain damage course; d) eNCAM appears to be more sensitive compared to NSE. Absolute values of ~erebellar uptake of Tc-99m HMPAO were obtained in 33 healthy volunteers and 13 patients, suffering from probable dementia of Alsheimer's type (DAT), by means of calibrated point sources used as external standard. If necessary, mostly for stressed volunteers, uptake values were corrected to the rest heart rate value (HR) using the previously described equation Auptake = -8.35AHR. Indlvidual brain vol~me (BV) was calculated using the sum of" all voxelB, above a 35% threshold of the maximal value of all slices, converted using the single voxel volume. The ~ean brain volume in the reference group of 18 ~en and 15 women with a mean age of 41 years(22-62) was 1350mi. The DAT group consisted of I0 women and 3 men with a mean age of 76 years(67-83). For DAT patients a reduced brain vol~L~e of 15% was observed compared to the gender related healthy younger volunteers. Body surface (BS) was calculated from the height and weight. Lower body surface values were obtained in the DAT group. Cerebellar rSU (mean +-SD) is expressed in I0-' of the injected lipophyllc dose per cm 3 brain tiBsue obtained in a II mm square region over the highest activity of the cerebellum. A body surface correction factor BS/1.73 is applied followed b y a brain volume correction factor BV/1330, resulting in uniform measurements for different subjects. Men Vol (18) Women (15) DAT (13) After applying heart rate, body surface and brain vol~me corrections, normalized uptake values are obtained. Even in a pathologic older population, in which despite of the pathology, the cerebellum can be considered as normal, for the cerebellar region the same uptake is obtained as in normal healthy volt%nteers. Single Photon Emission Tomography (SPET) brain scans, performed with 99mTcHMPAO, may be evaluated with visual and/or semiquantitative methods of regional analysis, which improve the image interpretation, but whose reproducibility must be carefully assessed. The aim of this study was to evaluate the intra-and inter-observer reproducibility of 3 semiquantitative methods in two groups of patients. In the first group -8 patients: 2 normal (N), 4 with cerebrovascular disease (CVD) and 2 with dementia (D) -the studies were acquired with a single head rotating gamma camera (Apex SP4HR Elscint, Israel). In the second group -10 patients: 2 N, 4 CVD, 4 D-a high resolution, brain-dedicated annular system (CERASPECT, DSI, USA) was used. On four selected brain slices, placed at standard levels above the cantomeatat (CM) reference plane (+ 2, 3, 5, 6 cm, respectively), one senior clinician and one first-year resident applied at both groups of patients three different sets of regions of interest (ROI), linearized to the cerebellum and consiting of: A) fixed -number and -size polygonal ROIs, B) multiple hand-drawn ROIs, and C) semiautomatic segmentation of a treshold-based, cortical ROI, plus manual definiton of deep grey matter (DGM) structures. One week later, the analysis was repeated. In both groups no significant intraobserver variation was found with any of the 3 methods. The cortical ROIs of both groups showed no difference when analyzed by the two observers with any method, while, in the first group of patients, DGM ROIs resulted significantly different (p< 0.005) between the 2 observers using method B and C. In the patients evaluated with the brain-dedicated camera no difference was evident for the DGM ROIs with all methods. The data suggest that, using a high resolution system, inter-indivual variability does not affect the measurement, while, at lower spatial resolution, the choice of the semiquantitative method becomes critical for the definiton of DGM ROIs. Recently MATSUDA et al, reported a non-invasive and relatively simple procedure for estimation of total and hemispherical cerebral peffusion by calculation of a brain perfusion index (BPI) from determination of the unidirectional influx constant of HMPAO. According to this evalutations the BPI was determinated for 57 pts. suffering from various disturbances of cerebral perfusion. The radionuclide passage in the first minute after bolus injection of 750 MBq 9~Tc-HMPAO was monitored with a dual head large field camera positioned over both, brain and thoracal region using a rapid sequence of 2 frames/see. A graphical analysis of curve data obtained over aortic arch and whole brain as well as both hemispheres give the influx-constant (k,). To receive the BPI the ku -values were correct for individual ROI-values. Mathematically we can show that the graphically estimated ku is a product of a influx constant (which is nearly the same in different patients) and the part of cerebral blood flow from cardiac output. Results showed a closed correlation of calculated BPI with perfusion and the degree and number of perfusion disturbances supposed by an combination of results of physical examinations, SPECT, rentgenologic angiography, XCT and/or MRI. In patients without or with minimal disturbances of cerebral blood flow a negative correlation from BPI with age was seen. BPI-values obtained from a curve fit done between the 5.-15 s compared with those between 10.-20 s show a small reduction of BPI for later time points. This finding may be attributed to fast back diffusion. If a standardisation for individual conditions of acquisition is done, this technique can complete as a helpful adjunct routine SPECT studies in a quantitative manner and alows the quantification of brain perfusion enhancement aider injection of acetazolamide. I C Dormehl, W.P Pilloy, N Hugo, N Rossouw AEC Institute for Life Sciences, University of Pretoria, Medical University of Southern Africa, Pretoria, and the National Accelerator Centre, Faure REGIONAL CEREBRAL BLOOD FLOW PATTERNS USING 123I(IMP) AND 99mTc-~PAO WITH SPECT IN ANAESTHETISED BABOONS N-isopropyl-p-(123I)-iodoamphetamine 123I(IMP), with long-acknowledged properties of a good tracer for scintigraphic regional cerebral blood flow investigations, can be considered a second tracer in a dual-isotope SPECT study with 99mTc-H~P~O for brain-stress testing, eg. after pharmacological intervention with acetazolamide to reflect on vasedilatory reserve. Necessary are identical 99mTc-~PAO and 123I(IMP) distributions in the normal brain, and again in the acetazolamide compremised brain to render diagnostically meaningful "stress" differences with pathology, Regional cerebral distributions of 99mTc-~4PAO and 123I(IMP) were here investigated by twc immediately consecutive SPECT studies, corrected for 99mTc counts in the 123I-window, in the normal baboon (n=6) and the stressed baboon (n=6). Coronal Slices were generated as input for a circumferential profile programme. Nine segments of four circumferential profiles on four equidistant transaxial slices were appropriately normalised in order to compare HMPAO and IMP distributions. Regions of interest were placed on the total brain in corresponding slices and the counts/pixel used in a comparison of the ratios of uptake from the two tracers, (IMP:HMPAO) for the norsal and later the stressed baboons. These uptake ratios, as well as the quality of the SPECT images, suggest better cerebral uptake of the IMP, and a lack of adequate agreement in the regional distributions of the two tracers for beth the normal and the acetazolamide ccmpromised animals. This finding would exclude a dual-isotope brain-stress test as proposed. This study was undertaken to determine the normal Tc-99m HMPAO brain SPECT pattern in adults. 10 volunteers, aged 20 to 30 years,were recruited: all were in good health, had no medical history and their neurological examination was normal. 555 MBq of Tc-99m HMPAO were injected in a quiet room with open eyes, followed by 2 successive 360 ° SPECT acquisitions. In each subject, this procedure was repeated 2 weeks later. Reconstruction, using the filtered backprojection method, allowed to obtain transaxial, coronal and sagittal slices ( 2 pixels thick = 1.3 cms ). The results show that the anteroposterior tracer distribution, measured on sagittal slices, was similar, in each subject, for the 4 acquisitions. Coefficients of variation of the cortico-cerebellar and cortico-cortical indexes didn't exceed 5 %. Right / left tracer distribution, measured on transaxial and coronal slices with a 9 cm 2 ROI showed asymmetries up to 16.9 % using a Wiener filter and no orbitomeatal reorientation ( OMRO ), 13.3 % using a Wiener filter with OMRO, and 13.1% using a Hanning filter and no OMRO. For the 40 studies, considering 12 % as upper limit of normal values, we observed abnormalities in 8, 1 and 1 studies using respectively a Wiener filter without and with OMRO, and a Hanning filter without OMRO. The localisation, extent and quantitative importance of these asymmetries varied markedly in 2 successive acquisitions as well as in acquisitions obtained at different days, suggesting that these asymmetries are artifactual. In conclusion, these results suggest that important right / left asymmetries may be observed in Tc-99m HMPAO brain SPECT from normal adults. As these asymmetries are strongly dependent on technical aspects from the reconstruction procedure (filter, OM reorientation, ...), it is mandatory that each center determines the normal pattern according to the procedure and the equipment used. J Farahati, SP MtiUer, B Kremens, E Eising, L Geworski, Chr Reiners. Nuclear Medicine and Pediatric Oncology, University Hospital Essen, FR Germany. Over the past 10 years the use of MIBG scintigraphy in the diagnostic workup and staging of children with neuroblastoma has expanded. The role of MIBG in the detection of skelettal involvement, however, is as yet controversial. Twenty children with neuroblastoma underwent both bone scanning (99mTc-MDP) and MIBG scintigraphy (I-123-MIBG) within 4 to 11 days. In 14 children the studies were performed at staging before any treatment. 13/14 had histollogicaly proven bone marrow involvement, and 10/14 had bone metastases. Four children were in complete remissio n. In addition 2 children were studied with suspected neuroblastoma, which were later proven to be Wilms tumors. The MIBG scan correctly identified 13/14 primary tumors, 12/13 patients with bone marrow involvement and 9/10 children with bone metastases (34/37 true positives MIBG). All 4 children in complete remission and the 2 Wilms tumors showed no MIBG uptake (6/6 true negatives MIBG). On the bone scans we could detect 5/10 patients with bone metastases and 5/13 with bone marrow involvement, and 8/14 primary tumors (18/37 true positives MDP). The 2 Wilms tumors were false positive on the bone scan (4/6 true negatives MDP). In one case the intensity of the uptake on the bone scan was superior to MIBG, and in one false-negative MIBG scan the bone metastases was diagnosed on bone scan. In comparison to bone scanning MIBG scintigraphy has a higher sensitivity and specificity. However, because of the importance of bone and bone marrow involvement on prognosis as well as therapeutic management of children with neuroblastoma, bone scintigraphy is recommended in children with negative MIBG scan. The therapy-resistant epilepsy (TRE) represents a diagnostic challenge during childhood in view of surgical treatment: therefore an accurate localization of seizure focus is required. In this paper, brain MRI and SPET with Tc99m HMPAO (PAO) and EEG were compared. The study was carried out on 37 children (20M and I?F aged 18 months to 17 years) with TRE: a l l possessed MRls performed elsewhere and EEGs performed in the Pediatric Department. All were submitted to the SPET study for further assessment: PAO (10 MBq/Kg) was injected in i n t e r i c t a l period in a quiet environment and state; in 20 non cooperative c h i ldren SPET was acquired on monitored sedation. Regional brain blood flow was considered pathological i f the abnormality was seen in more than one slice and view. The 4-16,mean 10 yrs) with a difference in leg length due to a unilateral congenital growth disorder underwent bonescintigraphy (Tc99m-HDP). Aim of the study was to determine the prognostic value in the calculation of leg length discrepancy at the end of growth. Regions of interest were chosen over the growth plates of proximal (PF) and distal (DF) femur, proximal (PT) and distal (DT) tibia. Right to left ratios and minimum to maximum count ratios were calculated, as was the contribution in terms of percentage of each plate to the total growth capacity of the leg. The migraticr~l disorders are a rare group of congenmtal malformaticns of the brain.They ccasist of the following entities: lissancephaly. pachygria, shize~cephaly, polymicro~ia, Lmilateral me~encephaly .These patients (pts) presented a variety of clinically se~ptmmps.The most conmcns were seizures,delayed development,failure to dmrive,microcephaly and eseasicnally hydrocephalus. We performed brain SPECT, CT and ~R an Ii children (~S years)with migraticrmnl ~ncmalies (i tmilateral raegalencephaly, 6 pachygria, 3 shizencephaly, i lissencephaly. ) SPECT showed cc~gruent or more extensive abnormalities wi~n CT and MRI lesions in 3 pts with shizencephaly, i pt widn lissencephaly,3 pts wii/n pachygyria.l pt wi1~ pachygyria demo~tra~ed no abnormality in SPECT ime~ing,however;calcificatic~ of bilateral capsulla interna was observed in MRl.Y~itiple focal perfusic~ defect was deteoed in 2 pts with pachygfria in SPECr, cne of these patients had abnormal ~I~G findings. But,there was no ischemia findir~s in CT and MR.In cme pt wili~ Lm_i]ateral hemimegole~cephaly, SPECr i m~ sho~ed hypoperfusion in ri~t hemisphere coP~rtm~t with CT and MR findin~.Moreover,additicrmnl focal hypoper~usicn in left parietal lobe was also observed wi~n ~4PAO SPECT We ccnclude that brain SPECT is a useful adjtnct to CT,MR,EEG studies in anomalies of neuronal ~l i o a . Moyamoya disease is a rare cerebrovascular pathology characterised by occlusion of cerebral arteries and development of an abnormal vascular network.Although moyamoya disease is originally thought to occur only in Japanese population, its occurance in other countries has also be reported. In this study, we aimed to evaluate the feasibility of 99m-Tc HMPAO SPECT study in twins with moyamoya disease (age:3 years) in comparison with MRI and angiography.99m-Tc HMPAO SPECT study demonstrated multiple focal and/or globally decreased rCBF in both twins.MRI demonstrated significant narrowing in both supraclinoid carotid and the medial cerebral arteries, especially marked on the right side.The diagnosis in moyamoya disease was determi~ ned by angiography. MR imaging has the greatest advantage of demonstrating blood vessels without requiring the use of the contrast medium.However; our results indicate that 99m-Tc HMPAO SPECT findings do correlate better with clinical symptomathology and angiographical findings.Also suggest more extensive brain involvement than did MR imaging.SPECT study is a noninvasive, inexpensive and useful modality in assessing the functional hemodynamie abnormalities in moyamoya disease. Dynamic liver angioscyntygraphy (DLA) turned out to be the sensitive method estimating the perfusion of the organ with regarding on the arterial and portal blood distribution. We decided to verify the clinical usefulness of this method in particular gastroeterological diseases in children. DLA was carried out in patients with chronic persisting hepatitis (CPH), hepatomegaly in acute infectious diseases (HASD), healthy carriers of HBs antigen (CHBs), congenital hiperbilirubinemia (CH) and malapsorption syndromes (MS). Normal results of dynamic liver angioscyntygraphy are among 70 -75%. The greatest reduction of the portal perfusion to 58,2 and 57,3% we ascertained in the group with CPH and HAID, a little lower-reaching to 63,2% was found in CHBs slightly but statistically significant depression to 65,8% we observed in patients with CH. In group with I~ portal perfusion was on the normal level. In patients with CPH significant depression of the portal perfusion coexisted with the hepatomegaly, increasing activity of AIAT, increasing level of bilirubin and IgG, in children with HAID concomited with hepatomegaly and increasing activity of AIAT. In groups with CHBs, CH the depression of the perfusion coexisted only with parameters resulting from creating these groups. In the group with MS all results ware on the normal level. With the help of the method the reduction of the liver perfusion, even without the early stage symptoms of the disease, may suggest earlier reduction of the portal perfusion before laboratory and ultrasonography signs appear. Making the DLA is most helpful in clinical diagnostic in children with CPH, HC and CHBs, recommended in patients with HAID, giving not much information in children with MS. Metastatic brain tumors, menengiomas and abscesses may show % 201 uptake besides low and high grade astrocytomas in the early SPECT images obtained 10-20 minutes after TI-201 injection. In this study, we aimed to investigate the role of quantitative early and delayed TI-201 SPECT imaging in various brain lesions. Nineteen patients with brain lesions were included in the study (Age: 45-68; 11 M, 8 F). 3 mCi TI-201 was injected. 15 minutes and 3 hours after the injection, SPECT imaging was performed using a large field-of-view camera (Toshiba -602) with a low energy general purpose collimator. Sixty-four images of 30 sec duration in 64x64 matrix were obtained. Symmetrical ROrs were drown over the lesion and contdateral normal tissue on the early and daleyed transaxial slices. Thereafter, early and delayed lesion (L)/normal tissue (N) ratios were calculated. Retantion Index (RI) was obtained for each patient using these ratios. Delaved L/N RI : x 100 Early L/N For the reason that primary malignant group is limited to a patient with anaplastic astrocytoma, statistical evaluation was not performed. In conclusion: 1) The origin of the brain lesions cfinnot be predicted with early and delayed quantitative TI-201 brain SPECT 2) If the question is specified to the differential diagnosis between two groups-for example; infection and metastasis, or infection and primary brain bening tumor-it might provide useful information for the clinician. Imaging diagnostics in brain tumors normally means CT/MRI imaging. The aim of this study was to find out if there is an improvement by adding functional imaging such as PET and SPECT.Out of a group of 65 patients with brain tumors 49 were selected (17 high grade gliomas, 12 low grade gliomas, 14 meningeomas,6 metastases). SPECT: 130 MBq 201-Thallium and 600-750 MBq 99mTc-HMPAO respectively were injected. Data acqusition: 5min.p.i. a 360 ° study, 128x128 matrix, 64 frames (30sec.each) was aquired. The quantification was done in ROI technique. For thallium study a ratio tumor/normal tissue was used. PET:after overnight fasting 200 to 350MBq 18-FDG were injected. 30min.p.i. three emission scans ( 10 min.each) were acquired. For quantification ROI technique was used. All patients were provided with CT or MRI scans respectively and were given biopsy or surgery of the tumor. In high grade gliomas the thallium ratio was 1.5-2.9, in low grade gliomas 1.2-1.5 and in meningeomas 3.1-8.5 respectively. The perfusion study showed an increased uptake for vital tumor tissue in high grade gliomas (14/17). Low grade gliomas (9/12) showed a circle-enhancement with low central uptake (necrosis, cyste). In meningeomas the perfusion uptake declined dramatically. For glucose metabolism high grade gliomas (17/17) showed an increased uptake, whereas low grade gliomas had partly increased and partly severely decreased uptake values. Meningeomas showed a low uptake and metastasis differed from high to low uptake values. The different tumor types showed different patterns in perfusion, thalium uptake and glucose metabolism. The combina-tion of morphological and functional imaging can apparently increase the specificity of diagnosis. Especially glucose metabolism gives datas about the activity of important centers in the brain, usefull for the planning of surgery. The inlroduetion of new therapies for ptinmW brain tomcum Ires lead to a better local eomrol aud, in selected groups of patianm (pts), Inc~sed survival rotes. Nevertkeless "l'ranslsissioa Computerized Tomograpl~ (C-q) and Magnetic Resottanee Imagiug are unable to reliably distinguish pemistent and recurrtmt minor front post-therapy neerasis or edema. Thallium 201 s.dmlgraphy has a lflgh sensitivity for detacting viable tumour.Prelhnhtary studies revealed tlmt 99roTe I'IMPAO may provide progmmtle Information concerning turaour respoose to d~mpy, The ahu of the study was to deteruda= the acuura¢7 of sequential 20iTl and 99raTe-HMPAO SPECF for deteethtg recument turnout, SPECr images were visually haerpreted and semlquamitative tumour uptake ratloe wet# corn!tared with the presence or absence of residual/recurrent tumor d e t e r m l~ IV stereom~,le biot~y or clinical aml radiological outcome. We studied t8 pm (13 M, 5 F), mean age 41 yearn (22-75)~ with clinical deterioration after terapy for astrncitonm ( Grade I/l1-6 pin ; Grade II//IV .9 pro), olJgodeadrogUonm (12 pls) and lhffoma Opt). Mean interVal betweett diagnorAs and SPF£TF vats 30 months. All tmtleuts were ~bmitted to ptmtlous ¢x~nud radlatltm therapy (RT} (|2 after surgery) mad I0 also to ehem0thempy, After Lv. Injection of 74 -111 MBq of 201TI hratgea were acquired (64 Images, 360 °, 30 seg/lnmge, 74 to 80 KeV #~otolx~k), Without moving the Pt 740 MBq of 99roTe HMPAO was Lv. injected, and another s p l~ study performed (64 inmges, 360 °, 30 seE/image , 140 KeV pbotolmak ), Each SPECT study was assessed visually by two indeI~"ndent obsereem for abnonnnl reglozm[ tracer up(ake mid judged to be 1 1~ l~odetate Or ~OW rehllv~ to the eontraluteml Ileu~phere uptake. Semlquantiteflve t0mor/Im~l~l~ound mdoe wera obtained from lrremdar ROls dmvm In II~ 20l"rl ~ jdleo~'wlth the hlgklmt cutua det'mlty. During follow-up zteurolo$1eal examination and c r we~ l*rffrmed in MI l~ mxd biopsy in 6 pts. Reeurreat mraor w~s present in 12/18 pts. Elev(m of tho~ 12 pt~ rdlowcd htereased 201"I"1 uptake (1 low, 8 moderate, 2 high). 99roTe I-II~AO gP~'T showed deoreased in 10 pts and low/moderata uptake la 2 la~ la 316 l~s without recurrent rumor 20lTl uptake'w~ normal~and in 3~mm increased, hx all the 6 pts 99inTo I'~AO ~ normal " The mean values of ~TI tumor/background tatloelfor pm wlth .mad without tumor recurr~tee wet* 3.65-~1.84 and 1.26-'0.35 (p<0.05). In our study, 20tTI -SPECr was a reliable mathbd for the.klmtlflcatkm of tumor recurrence, BRAIN TUMORS G R A D I N G The aim of this pilot study is to evaluate Thallium (T1) 201 SPECT i brain tumour grading. We performed T1 20l SPECT on 30 patient with supratentorial brain tumours. Suspected diagnosis was as follows 17 grade IV, 2 grade III, 1 grade II astrocytoma, 2 metastatic brai: tumours, 2 primary brain lymphoma, 2 radiation necrosis, 3 unknow~ processes. T1 201 is accumulated in brain tumour, not in normal brain SPECT imaging was performed 15 min after IV of 148 MBq of TI 201 with a single head tomographic camera (64x30sec/360°64x64 matrix) Region of interest (ROI) were drawn on the transaxial slice showin l the greatest tumour activity. For comparative measurements ROI wen determined on the homologous controlateral slide, on the controlatera scalp and over the whole cerebral contolateral hemisphere. Thre~ tumour T1201 uptake indexes were calculated using the average count~ per pixel for the tumour and the control ROIs. Mann Whitney test wa., used for statistical analysis. T1 201 indexes was high in 26 patient.' (group1) and low in 4 patients (group2). In the first group T1 201 i n d e x e s ranged to 1.35-5.97 (mean 2.64) for index 1 (Tumour/controlateral), to 0.88-3.45 (mean 1.33) for index (Tumour/scalp) and to 1.4-6.4 (mean 2.74) for index 3 (tumour/hemisphere). In the second group, T1 201 indexes ranged tc 0.88-2.2 (mean 1.37) for index 1, to 0.43-0.99 (mean 0.6) for index 2, and to 0.81-i.93 (mean 1.25) for index 3. There were significant statistical differences between the 2 groups for the three T1 201 uptake indexes : p = 0.0028 for index 3, p = 0.0072 for index 2 , p = 0.0087 for index 3. Predictive value of T1 201 indexes seems good : if index 1 >1.3 and index 2 >0.9 and index 3 >1.3 sensitivity increases to 92% and specificity to 100%. T1 20i SPECT may help to primary brain turnouts grading, and to differenciate radiation necrosis versus recurent glioma. We continue this study to determine exactly threshold indexes between low and high grade gliomas. With dedicated brain gammacamera and multimodality computer it could be possible to improve anatomical data by superposing SPECT images with MRI images, and with computerized automatic calculation to assess viable tumour volume ; it would be usefulness for patients therapy and prognosis. The aim of this study is to evaluate Thallium (TI) 201 brain tumors uptake indexes. We performed TI 201 SPECT on 30 patients with supratentorial brain tumours (22 astrocytoma, 5 others tumours, 3 unknown processes). Transaxial slices were displayed and added four by four in function of TI minor uptake, resulting in 10 transaxiai slices of 1,5 cm width. Regions of interest (ROI) were drawn on the transaxial slice showing the greatest tumour activity : a large one around all the tumour (ROI I), and a little one around the greatest TI tumor activity (ROI 1). For comparative measurements ROI were determined on the homologous controlateral slide : large (ROI I1) and little (ROI 2), on the controlateral scaip(ROlscal) and over the whole cerebral contolateral hemisphere(ROlcer). Six tumour TI 201 uptake indexes were calculated using the average counts per pixel for the turnout and the control ROIs. Mann Whitney test was used for statistical analysis. The three indexes calculated with little tumoral ROI (ROI 1) were not pertinent for primary brain tumor grading (p = 0.15). The 3 indexes calculated with large ROI was high in 26 patients (groupl) and low in 4 patients (group2). Index 1 (ROI UROI II) was at 2.64, (mean value group 1 = mvl) versus 1.37 (my2), index 2 (ROI I/scal) was at 1.33 (mvl) versus 0.6 (mv2), index 3 (ROI I/ROIcer) was at 2.74 (mvl) versus 1.25 (mv2). There were significant statistical differences between the 2 groups for the 3 indexes : p = 0.0028 (index 3), p = 0.0072 (index 2), p = 0.0087 (index 3). Based on the index cutoff of 1 for index 2 (ROI I/scal) sensitivity = 69% and specificity = 100%, on the index cutoff of 1.5 for index 1 (ROI U ROI II) sensitivity = 92 % and specificity = 75%, on the index cutoff of 1.5 for index 3 (ROI I/cer) sensitivity = 88% and specificity = 75%. In conclusion : brain tumors TI 201 uptake indexes are only valid if tumoral ROI is large. The choice of a 1.5 cm slice width is important on account of tumor heterogeneity and SPECT definition. Indexes permit to differenciate low and high grade glioma. The most specific is the index 2 (tumor/scalp), the most sensitive is the index 1 (tumor/controlateral region). The predictive value of this 3 indexes are good with index 2 > 1 and index 1 > 1,5 and index 3 > 1.5; sensitivity growth to 92 % and specificity to 100%. We continue this study to state exactly 1"I 201 uptakeindexes in gliomas, and to evaluate their clinical predictive value, and their usefulness for therapy following. It is known tllat most neoplasms of neuroendocrine origin express somatostatin receptors. This continuing study evaluates the in vivo uptake of a somatostatin analogue (pentetreotide) by intracranial tumors. We evaluated 49 patients, 30 males and 19 females (mean age 50y, range 19-81), with a variety of brain tumors. More precisely: meningiomas (n=11}, gliomas of various types and grades (n=24). pituitary adenomas (n=5), acoustic neuromas (n=5) and metastatic brain tumors (n=4L All patients had positive findings in previous examinations using other modalities such as CT and/or MRI scans. Planar scintigraphic imaging was performed at 6+1 hrs p.L following the IV administration of 2,2-3,0 mCi of 1111n-DTPA-Octreotide. The tumor/normal tissue (T/NT) uptake of the radiopharmaceutieal was determined and the T/NT ratio was then calculated. All patients (with the exception of those with metastatic tumors) were surgically treated within the following 48 hours. Histologic verification of resected tissues was performed in all cases. Positive scintigrams were obtained from all the meningiomas (11/11), in 20/23 gliomas, in all the pituitary adenomas (5/5) and metastatic tumors (4/4) and in 4/5 of the acoustic neuromas. The quantification of the relative uptake of the radiopharmaceutical by the tumors yielded the following T/NT ratios: In conclusion. 1) -the use 1111n-Octreotide may be helpful in the preoperative differentiation of meningiomas from other brain tumors in respect to the high T/NT ratio obtained. 21 -In the remaining tumor types wNch were positively imaged the T/NT ratio did not show any significant differences between the different histologic types. An extract from wall of the bacterium Nocardia opaca prepared as disclosed in the German patent P 3510795 supplied by one of the authors (U.Ehrenfeld) was proved in former animal experiments as an immunomodulating substance. After administration of this preparation radiolabelled by In-111 or Tc-99m and in tracer amotlnts an elevated radioactivity uptake was observed at various sites of increases enzymatic activity as well as in Walker cacinsarcomas. Therefore, the reliability in diagnosing of different types of malignant tumors was studied by us. Planar imaging using a large field camera equipped with a MEHR collimator took place 3 hrs. pi. of the Tc-99m-labelled immunomodulatot completed by SPECT for doubtful cases. Images were evaluated by visual interpretation as well as in a semiquantitative manner. 105 male and female pts. were studied suffering fromfollowing types of primary maiignomas or metastases: breast cancer, sarcomas, malignant tumors of urogenital and gastrointestinal system, melanomas and neuroendocrine tumors. 23 lesions were proven histologically, whereas the remaining number of scintigraphic findings were confirmed by CT and MR/. Overall sensitivity of tumor detection was 0,97 % if cut off point was set at a uptake ratio of 1.30. The mean values of ratios differ from tumor species to species with the highest mean values for ratios of sarcomas. Advantageously, the diagnostic application of the Tc-99mlabelled IMM is not limited to a single tumor type but seems to be successfully in a broad range of different types of malignomas. Therefore, from clinical point of view the IMM seems to be suited to used for recognition of malignomas additionally to other well known tumor seeking agents. Further studies will be directed to consider the question of specificity. The aim of this study was to compare the biokinetic properties and imaging capabilities of an anti-CD7 antibody, using the 131I labeled complete lgG and F(ab')2-fragment and the 99mTc labeled Fab'-fragment in a nude mouse model. The CD7 molecule is a 40kD membrane protein, which is expressed by mature and immature T-lymphocytes. It is not expressed on a variety of non hematolymphatic humaal tissues. 29 nude mice with T-cell acute lymphoblastic leukemia cells (CEM cell line; 0.75-3cm 3 turnour volume) were included. Scintigraphy was performed with a pinhole collimator (Siemens Basicam gamma camera, 15min/image) and data stored in a 256x256 matrix (Max Delta computer system). Whole body kinetics were calculated by ROI technique. The ratio turnout activity / whole body" activity increased: for the complete antibody from 16% at 24h pi up to 93% I0 days pi, for the F(ab)2-fragment from 21% at 24 h pi up to 88% 10 days pi, for the Fab'fragment from 30% lh pi up to 40% 2h pi, which declined to 20% 72h pi. The complete antibody showed whole body retention with biological half life of 6.5 days, the F(ab')2-fragment of 3.7 days and the Fab'-fragment of 0.5 days. In conclusion, the Fab'-fragments achieve very early maxtmal percentage of the whole body activity in the tamour region, but in contrast to the complete antibody and the F(ab')2-fragment activity in the tumour region declines. Both effects can be explained by the more rapid whole body excretion of Fab'-fragments and their faster rate of extravasation. Presumably, there is an internalization of complete IgG and its F(ab')2fragment leading to stable tumour binding, whereas Fab'-fragments have lower affinity and no internalization takes place, leading to subsequent washout. Various in vivo and ex vivo imaging techniques were used to evaluate and quantitate 1-123 iodomethyltyrosine (IMT) uptake in primary brain tumor in rats. Quantitative imaging using tumor imaging agents TI-201 and Tc-99m IvIIBI was performed for comparison. A total of 30 animals with transplanted gliosarcoma was studied. The animals were imaged using pinhole planar and pinhole SPECT. At completion of imaging, animals were sacrificed, pinhole planar ex vivo images were obtained, and well counting of tumor and control brain tissues was done. Tumor to non-tumor (T/NT) ratios on images were determined using ROI techniques. The images showed increased I-123 IMT uptake in tumor compared to the activity in the surrounding normal brain. T/NT ratios were 1.4+0.1 and 3.0~0.3 on planar and SPECT studies respectively, 2.9±0.5 on ex vivo images, and 4.4+2.2 in thc wcll counter. Increased tumor uptake of TI-201 and Tc-99m MIBI was observed with T/NT ratios of 1.9±0.4 (MIBI) and 2.1±0.7 (TI-201) on planar images, 10.5±2.1 (MIBI) and 5.6±2.0(TI-201) on SPECT images, 10.9±4.8 (MIBI) and 7.1±2.4 (T1-201) on ex vivo images, and 9.0+2.6 (MIBI) and 5.6±1.6 (TI-201) in thc well counter. The selective, increased uptake of 1-123 IMT in gliosarcoma observed using high resolution imaging methods, is less than observed with T1-201 and Tc-99m MIBI. However, the findings are adequate to suggest that quantitative metabolic brain tumor imaging is feasible using high resolution SPECT with an I-123 labeled amino acid analog in order to visualized viable tumor. The aim of this study was to compare the visualization of brain tumors with Iodine-123-Methyl Tyrosine (I-123-MT) and Indium-lll-Octreotide (In-111-Oc). We used 1-123-MT (FZ-Seibersdorf), administering 222 MBq and planar images were performed 10min and lhr after application. In 5 pts SPECT images were performed too. Not earlier than 48hrs 244 MBq In-111-Oc (OctreoScan®, Mallincrodt) were injected and planar images 4 and 24 hrs after application performed, in 9 pts SPECT images were performed (4hrs p.appl.). A digital Anger camera was used for data acquisition and processing (APEX 409A, Elscint). A total of 12 pts (8male, 4 female; age ranging from 45-71 yrs) were investigated. Using a region of interest technique tumor-to-brain tissue ratios (T/BT) were calculated. Diagnosis of tumor was established by neurosurgical procedures. 6 pts with glioblastoma showed a high uptake with In-111-Oc (T/BT: 1.7+0.5) and also with 1-123-MT (T/BT: 1.5+0.4 (10') and 1.45+0.45 (lh)). In 2 meningiomas the images with In-111-Oc were very good (T/BT: 3.1, 3.6 (4hr pl)) and were negative with 1-123-MT. In 4 metastases we found a low uptake in 2 pts with 1-123-MT (T/BT (10'): 1.3 and 1.25; T/BT (lh): 1.25 and 1.2 and In-111-Oc (T/BT (4h pl): 1.6 and 1.4). These were pts with brain metastases of adeno carcinoma. In two pts with brain metastases of small cell lung cancer we found good images with both substances (I-123-MT T/BT: 1.6 and 1.7 (1 h) and In-111-Oc T/BT: 2.5 and 2.6 (4h pl). In summary, glioblastoma showed concordant images with both substances and also metastases, meningiomas showed discordant images. SPECT acquisition is possible with both substances and sometimes advisable. Twenty-three patients underwent PET examinations (Siemens ECAT 951R) prior to laparotomy. Dynamic FDG-PET scans of the pelvis were obtained for 60 minutes followed by PET imaging of the whole abdomen. Standardized uptake values for FDG were calculated based on attenuation corrected images and related to histological findings. Fourteen patients with primary and two patients with recurrent ovarian cancer had an increased, but heterogenous FDG uptake (SUV 5.4-+2.3). Necrotic/cystic areas could be clearly seperated from metabolicly active tumor sites. Five intraabdorninal abscess Iocalisations (n=3) also showed an intensive FDG accumulation (SUV 9.8+3.4). One patient with ovarial cystoma (SUV 1.1) and one case with ovarian borderline carcinoma (SUV 1.3) had low FDG uptake. In patients with benign cystic lesions (n=2) no significant FDG-uptake was seen. In areas with questionable CT-findings, FDG uptake aided in the accurate definition of metastatic tumor spread. In conclusion, differentiation between abscess and malignancy may be limited in patients with large pelvic masses. Correlation of FDG uptake with CT and sonography however adds diagnostic information. FDG-PET imaging is extremely useful in the Iocalisation of viable tumor tissue in new or recurrent ovarian cancer and may therefore guide surgical interventions. Several authors had reported on the value of IMLSc as a prognostic variable (PV) in BC. However, their conclusions might be criticized because they only take into account -as other potentiaJ PV -the axillary (ax) nodes status, Therefor, the follow-up (FUp) data of 860 patients ( mean FUp = 5 y. ) operated for histologically proven BC from t 2 / 1 9 7 8 to 12/~989 have been reviewed and analyzed ( Free Disease Interval curve, Delay Before Generalisation curve, Survival curve, Kaplan-Meier actuarial method, Logrank Test ) with regard to the various progonstic variables :clinical staging (CSt), ciinicat size (CSz), anstomopathological status of the ax nodes (AxAP), results of the IMLSc (IMLSc), hormonat ( estrogen ) receptivity (ER), hormonal treatment (HTt), menopausal status, age, differenciation of the tumor,.., in our population and whatever was the considered end-point ( FDI, DBG, S ), the main PV ( univadated analysis ) were the CSt or the CSz, the AxAP, the IMLSc ( 2p < 0.0001 when c~ass~fied as pathologic ), the HTt and the £R. When IMLSc was introduced in a Cox Modet ( Multivariated analysis ) with the other potential explicative PV, the scintigraphic result remains as one undependent explicative variable for the prognosis of BC. It is concluded that IMLSc represents one undependent PV in BC and that its result has to be taken into account in the management and treatment of BC. Breast cancer frequently occurs in women and patients (pts) prognosis has been shown to improve with early detection and aggressive treatment. Clinical examination, mammography (mmg) and fine needle biopsy are frequently inconclusive in order to characterise breast nodules. Aim of the present study has been the evaluation of the accuracy of Tc99m MIBI imaging to define malignant lesions and its possible role in the diagnostic strategy. Our study group consisted of 17 women affected by breast lesions detected by mmg who should be considered a random sample from the clinic.. All the pts were treated surgically and had a histological evaluation. 370-500 MBq of MIBI were injected in the antecubital vein opposite to the involved breast and the scan was performed immediately and after 2 hours. Pts were imaged by planar scintlgraphies obtained in anterior and anterior oblique views. Two independent experienced observers blinded to clinical and histological data interpreted the MIBI studies. Any disagreement was resolved by consensus. In 15 pts solitary nodules were found (tumor size = 2.4 +/-.9 cm); 2 pts suffered from diffuse pathology (carcinomathosis mastitis). In 13 pts a malignant disease (54% with positive mmg, 46% inconclusive) and in 4 benignant lesions (75% negative, 25% doubtful at mmg) were found. MIBI imaging showed 86% sensitivity and 75% specificity with an overall accuracy of 82%. Particularly MIBI imaging gave correct interpretation in 72% of pts with inconclusive mmg. Thus MIBI scan could be considered a useful tool, complementary to mmg, in the screening of breast nodules. Several papers and communications have reported -on limited semen of patients -encouraging reeutts for the detecion and diagnosis of 8C w~th Ti~. ~e present study was unde~aken in order to precise the sensitivity of the technique with regard to its po~entiaJ limitations ( righ~ or le~ location of the tumor, ~he size,... ), To ~he date of Februa~ ZOth, planar imaging ( ant, ~at and pos~ obt views, 5 m~n, per vfew ) of 30 dgh~ (~) and of 30 ~e~ (h) brews h~e b~n obt~n~ S ~ ZO m~n. ~e r ~V {nje~on of 2 ~o 3 mitliC~des of 201TL TISc were pe#ormed preoperativeIy in 2~ women and in ~ man with mdiotogicat~ and/or c~inicalIy suspected mamma~ carcinomas of one breas~ ( Group ], R = 16, L = 9, hismlogfc=ily proven ~o be malignant in ~2 cases ). ] 1 ~umou~ ( 9 maiignan~ 8 R and 3 L ) were less than (TI) and 14 ( I ben~, 8 R a~ 6 L ) more (T>~} ~an Z cm. Five patten= were inves%~t~ as Cont~ and as pa~ of ~o~low-up a~er tumorec:omy ~nd radiotherapy ( Group 2, ~ suspicion of mamma~ re~a~8 ). Sc we~ c~ssSified Tt+ if focal area of sct~i~ was dete~ed in the bre3s~, T~-if no~ and TI? if unconclusise. The ~ree benign tu~uts (R) were TI-, Among ~e contrala¢e~i bte~s of G¢ 1 ~nd the brea~ of G¢ Z. none was classified T~+ ~ 4 L we~ TI?. We are evaluating the safety and efficacy of a Tc-99m labeled Fab' anti-CEA antibody fragment ( I~J -4 , Immunomedics, Inc.) for preoperative evaluation of the breasts and axillae in patients (pts) presenting with breast ca. Nine pts with i0 primary breast ca (one bilateral) received IV injections of 1 mg of IMMU-4 labeled with 740 MBq of Tc-99m. Planar whole body and thoracic SPECT images were obtained 6 hours post injection using a dual-head camera. In 7 pts SPECT imaging for 30 minutes was performed at 24 hours. The image results were compared with pathologic examination of surgical specimens in all pts. The primary breast ca was confirmed with RAID in i0 of I0 cases (sensitivity=100%). The smallest tL~mor found was i.i cm. Two pts w i t h u n e x p e c t e d contralateral breast uptake are being followed. In the 9 pts who had ipsilateral axillary exploration, scans were true-negative in 4, t r u epositive in 3, and false-positive in 2 (both of which showed only slightly elevated activity). Delayed SPECT imaging improved tumor detection in 4/7 pts. The only adverse reactions were mild itching at the time of the injection in two pts and a ~etallic taste in one pt. H A M A titers remained normal in all pts (in other studies <1% of pts show elevated H~A titers). Tc-99m IMMU-4 Fab' appears promising for detecting primary breast ca and axillary metastases. SPECT at 24 hours'is feasible and appears to aid diagnosis. So far, the role of the bone scan in the routine screening of breast cancer patients for metastases at presentation and during follow-up is widely agreed. However, this early enthusiasm has been recently decreased somewhat due to the relatively low true positive yield and the measurable rate of false positive studies. Furthermore the main indication for bone scanning is exclusively dealing with the osseous metastases status of the malignancy while the possible soft tissue secondaq lesions cannot be explored but surgically only detected. Since m any histopathologie type of breast cancer, somatostatin receptors has been found to be more or less, we attempt by the present to evaluate the use of radiolabelled Pentetreotide as a possible screening method in breast cancer suspected women; thereby delineating any soft tissue participation (lymph nodes etc)as well as detecting occult secondary osseous lesions. In 23 The aim of this study was to evaluate the sensitivity and diagnostic accuracy of the directly 99mTc-labeled F(ab')2 fragments of the monoclonal anti-CEA antibody (MAb) F023C5 in patients with colorectal and other CEA-expressing tumors. The MAb (M-CEATEC Fab, Sorin Biomedica, Saluggia, Italy) was labeled with 1480-1850 MBq (1 ml) of a fresh technetium generator eluate. After removing 12-20% remaining free pertechnetate by ion exchange chromatography, 740-1295 MBq (0.25-0.5 rag) were injected iv. Totally 50 patients were investigated. Planar scans were performed 1, 4 and 24 h pi, SPECT after 4 and 24 h. All scintigraphic results were correlated to morphologic imaging procedures (CT, MRI) and finally to histology after surgery or biopsy. The following lesions could be detected (scintigraphically pos. / all lesions): 4/4 colonic primaries, 15/15 locoregional recurrences, 24/31 liver metastases (scintigraphically hot or with warm rim), 11/11 lymph node metastases, 1/4 lung metastases, 2/3 brain metastases, 2/3 bone metastases and 4/5 peritoneal carcinoses. Positive tumor detection was possible in 16% as early as 1 h pi, in 82% 4 h pi. SPECT was superior to planar scans in 43%, especially with respect to locoregional recurrence and liver metastases. Previously unsuspected lesions were found in 42% of patients. Summarizing, the use of 99roTe-labeled F(ab')2 fragments could yield additional information to conventional imaging procedures (CT, MRI) in the staging of colorectal cancer patients. The sensitivity for ]ocoreg. recurrence and lymph node metastasis detection was especially high, despite the renal elimination of MAb fragments (SPECT indispensable). Bleomycln (BLM), a natural antibiotic toxic to dividing cells, has been used successfully for treatment of N&N cancer, as a single agent or combined with external radiation therapy. Therefore, the idea of combining radio-and chemotherapy using ELM complex (EMLC) is a fascinating possibility. In-III-BLMC was prepared from ELM sulfate, consisting of 13 alkaline glycopeptldes, with In-lll-Cl3, at low pH. Radiolabeled In-III-BLMC (subfractions A2a_c) (i00 MBq/mg) were administered to H&N cancer patients in escalating doses of 75 (4 pts) , 175 (3 pts) and 375 MBq (3 pts). The patients were imaged quantitively with garmaa camera, at least three times prior to surgery. scintlgraphic data were compared with tissue samples from surgery 48 h after injection. SPECT studies were also performed in 3-D format for comparison with high fleld-MRI (fusion imaging} . Serial blood and urine samples were collected for radiopharTnacokinetics. T~ for radioactivity was 1.5-3.1 h in serum and 1.4-3.7 h in urine. About 50% of the activity was excreted in urine within 3 h. In all patients > 95% of the activity was excreted in 22 h. In surgical samples following uptakes were observed: fat 0.02-0.09, bone 0.05, salivary gland 0.04-0.17, muscle 0.03-0.08, blood 0.04-0.08 and tumor 0.39-0.95xi0 -3 %/ID/g (at 48 h). From the imaging data, kichleys were the critical organ; the doslmetric estimate for a 3700 MBq dose, assuming a mean residence time of 5 h, was 2.4 Gy. The tumor dose was 0.66 ~Gy/~gq (a mean residence time of 16 h), in a 14-gram tumor (MIRD formalism) . Tumor T M was 16-49 h. The activity distribution and penetration into tumor tissue was not affected by the increasing injected activity. BLMC activity correlated positively with immunohistochemistry of the proliferation markers Ki-67 and Mib. Cell nuclear localization (autoradlography) and heterogeneous activity distribution was observed (beta camera). These data are compatible with In-III-BLMC being suitable for adjuvant Auger-electron therapy of H & N cancer. We suggest that In-ll4m would probably be the most effective Auger-emitter. Various antibody-based cancer imaging agents have b e e n developed and evaluated over the past decade, including different antibodies and antibody forms, radionuclides, and scanning p r o c e d u r e s . U s e of the Fab' form of anticancer M3%bs combined with direct labeling of SH-groups with Tc-99m has allowed the development of rapid and simple kits of low immunogenicity when i mg Fab' is used (less than 1% }£qMA incidence). A multicenter study of 382 patients with colorectal cancer given a CEA-MAb agent, ImmuRAID-CEA, revealed both safety and evidence of efficacy. In 122 patients with known disease by conventional imaging methods (mostly CT scans) and surgical followup, sensitivity in the liver, extrahepatic abdomen and pelvis was 83%, 78%, and 73%, respectively. The Positive Predictive Value for l e s i o n s was significantly higher when conventional imaging and antibody imaging were both positive (99%), than when conventional imaging was positive and antibody imaging was negative (68%). A n t i b o d y imaging also significantly increased imaging accuracy when combined with conventional imaging. In another s e r i e s of 88 patients with suspected recurrence, but occult disease, combining antibody imaging with conventional imaging significantly enhanced diagnostic accuracy, potentially improving clinical decision-making in 4 2 % of the surgical patients. In summary, this appears to be a rapid and simple test for disclosing colorectal cancer sites, including lesions in the liver, and appears to contribute significantly to presurgical evaluation of patients with colorectal carcinoma. (Supported in part by USPHS grant CA39841 from the NIH. ) S u n d a y , 21 A u g u s t -W e d n e s d a y , 24 A u g u s t 1 9 9 4 5 2 5 Fluorouracil (FU) has been used in clinical practice to treat colorectal carcinomas for more than two decades. The average response rate is lower than 20%. Since tumor response to FU chemotherapy necessitates the accumulation of the cytostatic agent in the metastases, PET with F-18 labeled FU can be used to assess the tracer concentration in the target area. We used a PET system to evaluate the FU uptake and trapping in patients with liver metastases prior to the FU chemotherapy. The target area corresponded to the largest tumor diameter and was determined by CT shortly before the PET study. F-18 labeled FU was administered together with S00 mg nonlabeled FU in order to obtain therapeutic concentrations. Sequential PET images were acquired for two hours beginning with the FU infusion. Standardized uptake values (SUV) were calculated from the PET cross sections two hours after tracer application. All patients received several cycles of FU chemotherapy after the PET study. In 2 pts with pulmonary metastases, 1 pt with kidney involvement and pt with recurrence of CC RIS findings were negative. Whole-body scan imaged 63% of described lesions, and 20-24 hours SPECT showed more lesions than 4-6 hours one (ratio 1,2:1,0). No correlation was found between CEA serum levels and RIS results. In conclusion our results suggest that RIS is a useful procedure in the follow up of pts with CC, especially in situation when the results of other diagnostic modalities are equivocal. SPECT imaging at 20-24 hours seems to be mandatory. The sensitivity of In-lll-Pentetreotide (SMS) whole body scintigraphy and SPECT in patients with tumor not detected by abdominal or thoracic CT, MRI or ultrasound (US) is not well examined.Using ii0 MBq In-lll-Pentetreotide, a HEAP-collimator, SPECT performed 4 and 24hrs p.i. (360 ° , 64steps, each 40s), we evaluated 2 groups of patients: I) 6 pats. (5 carcinoids, 1 insulinoma) in whom CT, MRI and US showed isolated liver metastases, refered for livertransplantation (LTX), SMS scintigraphy revealed additional tumor sites in 5/6 (i pleural, 1 abdominal, 2 skeletal, 1 lymphogen). The patient without extrahepatic tumor was transplanted. He is free of recurrence 3/4 year later. In 3 pats. the scintigraphy failed to detect some of the known liver metastases shown by CT. 2) 6 pats. with suspected GEP tumor (3 primaries, 3 recurrent tu) because of elevated hormon levels in 5 eases and a positive biopsy in 1 case. In all of them CT, MRI and US imaging was negative. SMS scintigraphy detected tumor in 2 cases (I local recurrence, 1 disseminated tumor) -true positive. In the pat. with positive biopsy the SMS scan was negative and the resection showed no tumor as well -true negative. In one pat. with a negative SMS scan and a suspectable angiographic finding, a curative resection was done -false negative. In the last 2 SMS scan negative'pats, no explorative laparatomy was performed, so the result is nonconclusive. Connl~slonsr-In pats. referred for LTX due to metastases of GEP tumors, the 8MS whole body scintigraphy detected in 80% foci not found by abdominal and thoracic CT, MR or US. Early use is recommended. In case of isolated liver metastases in SMS scan, completing CT, MR and US are required. -In pats. with clinical high suspicion of tumor not detected by CT, MRI or US, SMS scintigraphy showed true positive or negative results in approximately 50%. In more than 80% of the cases, primary hepatoceUular carcinoma (HCC) is associated with elevated levels of serum alpha-fetoprotein (AFP). Using specific radiolabeled antibodies as diagnostic imaging agents, AFP-antibodies may be useful diagnosing HCC. Eighteen patients suffering from ensured or highly suspected HCC were examined. In 12 of these markedly elevated serum AFP was evident. The radiolabeled (900 MBq Tc-99m) Fab-fragment (lmg), supplied as an instant labeling kit, was applied by infusion over 30rain. The planar and SPECT imaging was performed 6h and 24b p,i. In 12 patients there was a specific binding of the antibody to the tumor, seen at the rim of the tumor due to the physiological internal pattern of HCC compared to normal liver tissue. In all these cases the result could be positively correlated with the findings of computed tomography (CT) and biopsy. In four cases presenting elevated serum AFP, no specific antibody binding was found and no malignant lesion was evident in CT or biopsy. One of these showed an atypical increased uptake in the 6h-imaging Biopsy documented an area of highly vascularized tissue related to inflammatory changes due to hepatitis-C. One lesion in another patient with a normal level of AFP did not show specific binding of the antibody. In this case, the suspected lesion could not be ensured as HCC by biopsy. In one case metastatic disease in the lower abdomen was evident. One case showing two small lesions was diagnosed false negative. The preliminary experience in imaging of HCC using radiolabeled anti-AFP-antibody fragments clearly demonstrates the high potential of this method to diagnose HCC. With respect to the clinical impact, possible applications are recurrent tumors, non resectable tumors and the detection of metastatic disease. Immuneecintigraphy (IMS) was pellbrraed in lmtients (pts) with culorectal cancer in cases of known prnnm~ or suspected recurrence of dtsuase. To study the diagnostic usefulness of OneoSeint CR103 (OS) we examined three groups of pts (G-1,2,3). In (3-1 nine pts were examined with known prmlary colorcetal calmer, mlmediately preoperatively detecting the extension of disense. G-2 c~tained seven pts with suspected recurrence of disease, or~ to four years after operation. In G-3 five pts were examined with Inoperable rectum carcinoma after irradiation. In all cases (21 pts) the histological result was known. We measured the serum level of CA 19-9, CEA and TAG-72. Planar tmagas were obtained at 24., 72., 120. hours post OS injection from the whole body. We analysed the pictures visually and quantitatively/the ratio of target-background (T]tK3)L In G-I we rneastired after operation OS uptake of removed tumors, normal tissues and removed lymph nodes (in kBqlq), and deturmined the ratio of OS uptake of carcinoma and normal tissue (C/N). The content of CA 19-9, CEA and TAG-72 of the~ different tissues were measured as well. Our r~s~ts comlmred with the surgical, hiaological, CT and UH findin~gs were as folinves: 1.) OS uptake ef ¢olorectal camcer was ima'uased m 18/21 pro. False negative cases (3 pts) were in (3-1 two, because of low level of OS uptake of tltm~ (C/N of these pts were 1.5; 1.8 and in IMS positive cases C/N were 3.4-1 S) and in G-2 one, because of ~ size of tumor. (Sunsitivity85%). 2.) Memsmsus were observed with IMS in four eases in spite of negative results of CT and/or UH. We could not detect lymph node metastases in the pelvis preyed by CT end UH in 3/6 cases. (Sensitivity:77%). 3.) Inflammation (was after irrediatiun and in enlostoma) caused increased uptake of O~ in six cases, but we oould distingin~ Uunor from inflammation mmlysmg the value of T/BG during the series of images during the whole examinatien /comparing the 24.,72.,120. hours piealtesL (Specificity: 100%). 4.) Serum level of CA 19-9, CEA mad TAG-72 did not correlote with the positivity of IMS, but mild to severe elevation of one or more tumor markers were found in 15 pts of 18 IMS positive eases. hi ¢on¢insio~ OS-//VIS so~as to be a sensitive and specific method for detecting the primary enlurectal cancer and recurrence of disease, T1 201 SPECT was performed on 19 p a t i e n t s , 13 males and 6 females aged 28 to 73 yrs (mean 51), with nasopharyngeal carcinoma(NPC) h i s t o l o g i c a l l y proven to e v a l u a t e whether or not T1-201 SPECT was u s e f u l and r e l i a b l e for a s s e s s i n g the tumor v i a b i l i t y of NPC. T h i r t y seven Ti-201 SPECT s t u d i e s were performed for the follow-up study a f t e r r a d i a t i o n therapy in 9 of 19 p a t i e n t s and for the as sessment of tumor e x t e n t before t r e a t m e n t in the o t h e r 10 p a t i e n t s . Data a c q u i s i t i o n was started 5 min after the intravenous injection of III MBq of Ti-201 chloride using a three-head rotating gamma camera(Toshiba GCA 9300A) equipped with fan-beam collimators. TI-201 clearly accumulated to the tumor in 10 patients before radiation treatment and increased Tl-201 uptake by the lesion disappeared after the treatment. Three of 9 patients who were followed-up after radiotherapy developed apparent local recurrence and Ti-201 SPECT could definitely visualize these recurrent lesions. T i -2 0 1 S P E C T was very useful for detecting local recurrent tumor. High resolution SPECT system with the use of Ti-201 chloride is a new tellable and accurate diagnostic tool for assessing the tumor viability of NPC. The diagnosis of diffuse intraperitoneal spread of ovarian or colorectal carcinoma (carcinomatosis) is often difficult on the basis of visual analysis of immunoscintigraphic images. The purpose of this study is to assess the utility of quantitative analysis of planar In-111 satumomab pendetide images in the diagnosis of carcinomatosis. Quantitative assessment of monoclonal antibody scans obtained two to four days post injection was performed on 29 studies of patients with ovarian or colorectal carcinoma. Regions of interest 5 x 5 c m were m a d e over the right and left sides of the pelvis between the lilac vascular bundle and the iliac crest. The counts from these two regions were averaged and an uptake ratio was created by dividing these averaged counts by the counts obtained from a similar sized background region of interest over the femoral vascular bundle. These ratios were then correlated with surgical-histologic findings. In 22 scans on patients w h o did not have carcinomatosis nor focal tumor sites in either lower quadrant, there was a m e a n uptake ratio of 1.23 (range 0.78 -1.76, S.D.= 0.308). This compares with a m e a n ratio of 2.36 (range 1.70 -3.07, S.D.= 0.585) in seven patients with Confirmed carcinomatosis. The difference between these two means was statistically significant at p<0.001. Using the cut-off ratio of 1.80, all 22 scans without carcinomatosis were correctly identified. Only one of the seven cases of carcinomatosis fell below an uptake ratio of 1.80. Based upon this sample of patients, quantitative analysis appears to hold promise as a useful adjunct to visual interpretation of immunoscintigraphic images in the diagnosis of carcinomatosis. Establishing the malignant nature of a bone lesion by imaging procedures can be difficult. The aim of our study was to investigate the role of methoxyisobutylisonitrile-99Tc (MIBI) bone scan in diagnosing the malignant nature of tumor-like bone lesions. Methods: Patients with plain radiographs or computed tomography suggesting bone tumor were enrolled. Every patient was studied by conventional bone scan with MDP-99Tc and MIBI-99Tc. Only patients with firm pathologic diagnosis were evaluated. Statistical significance was established by chi-square test with the Yate's correction. Results: sixty-six patients were enrolled. In 55 patients, it was possible to establish a pathologic diagnosis of the bone lesion. MDP-99Tc scan was nonspecific in establishing the malignant nature of the lesion since most of the patients had a positive scan. Twenty-two out of 29 patients with pathologic diagnosis of a malignant bone lesion had a positive MIBI-99Tc scan. In sharp c~ntrast, 23 dut of 26 patients with pathologic diagnosis of benign bone lesion had a negative MIBI-99Tc scan (p<0.O01). The sensitivity, specificity and positive predictive value of MIBI scan for malignant bone tumor were 76%, 88% and 86%, respectively. Conclusions: MIBI-99Tc bone scan is a useful noninvasive test for the detection of the malignant nature of a tumor-like bone lesion. An imaging modality able to detect lymph node (micro)metastases of head and neck cancer could be important for staging purposes. In this study we investigated the applicability of L-l-[tlC]-tyrosine (TYR) for the detection of lymph node involvement in squamous cell carcinoma of the oral cavity. Seven patients with histologically verified No-N2c squamous cell carcinoma were studied. Patients received 370 MBq TYR. A total length of 21.6 cm was studied via 2 static emission scans (Siemens ECAT 951/31). Of 6 patients preoperative T 1-and T2-weighted MRIimages were available. Shortly after PET neck dissection followed. Comparisons were made between PET, MRI, and histopathology. In the 7 resection specimens of the PET-studied patients a total of 130 lymph nodes were present. In 11 of these nodes metastatic disease was found. All histologically proven metastatic lymph nodes were visualized with PET. In addition, 10 other lymph nodes were visualized, being either normal or reactive on histopathology. The smallest lymph node detected was 0.5 om in diameter, In all patients the submandibular and parotid glands showed high uptake of TYR. Preliminary sensitivity, specificity, and accuracy can be calculated at 100%, 93%, and 94%, respectively. In comparison, in the resection specimens of the 6 MRI-studied patients 108 lymph nodes were present. Six nodes showed metastatic disease. On MRI, 4 nodes gave a true-positive and 4 nodes gave a false-positive signal. Consequently, the figures for MRI are 67%, 96%, and 94%, respectively. In conclusion: in the evaluation of lymph node involvement of squamous cell head and neck cancer TYR-PET can be a valid diagnostic tool. Our figures are favourable to those reported for FDG-PET. Among the Chinese of Taiwan, nasopharyngeal carcinoma (NPC) is the most common cancer in males and the third most cancer in females. The number of radiopharmaceuticals proposed for tumor imaging is in the hundreds, but only few have achieved widespread acceptance in clinical use. Both Thallium-201 (TL) and Tc-99m methoxyisobutylisonitrile (MIBI) uptake in NPC have been reported, yet no comparison study of these two agents using SPECT images has been performed for NPC. The aim of the present study was to compare the relative effectiveness of MIBI and TL SPECT for detecting NPC, A total of thirty two NPC patients (26 males, 6 females, age range 28-69 years) histologically confirmed by biopsy were studied. The dosage was 740 MBq for MIBI, and 74 MBq for TL. For both agents, SPECT images were obtained 10 to 20 minutes after intravenous injection, There was a period of 2 to I days between MIBI and TL images. All imaging procedures were performed using an Elscint APEX ECT 609R gamma camera and computer system. The image was interpreted as positive if there was significant uptake of MIBI (or TL) in the nasopharynx, As a result, 28 (81%) NPC patients showed TL tumor uptake while 24 (75%) showed MIBI tumor uptake. Our preliminary study suggests that I. both MIBI and TL SPECT imagings can be helpful in detecting NPC; 2. the sensitivi'ty of TL SPECT imaging in detecting NPC is slightly higher than MIBI SPECT imaging. Accurate preoperative staging is necessary for surgical treatment planning in patients with SCC of the head and neck. We compared metabolic imaging (F-18 FDG PET), morphological evaluation (MRI) and endoscopy with postoperative, histological tissue characterization. Tumor extent was evaluated by all three modalities. Lymphnode involvement was only assessed by PET and MRI, After injection of 370 MBq F-18 FDG emission scans of the head and neck region were performed. Regional FDG uptake was evaluated visually without knowledge of other clinical results. In addition regional FDG uptake was quantified by relating F-18 tissue activity to injected dose (SUV). Metastatic lymphnode involvement was defined by FDG uptake or by MRI diameter greater than 1.5 cm. All primary tumors were clearly visualized by PET (SUV: 5.4 + 3.1) and by MRI. Howewer, due to high FDG-Uptake in normal mucosa, tumor extent was overestimated in 6 of 8 patients. Endoscopy and MRI yielded better T-staging in 5, and 4 patients respectively. SUV in metastatic lymphnodes was 5.7 + 2.3. F-18 FDG-PET correctly identified N-Stage and lateralization in 7 out of 8 pts. One false negative lymphnode classification was due to a small, contralateral lymphnode (diameter: 0.9 cm) with only partial metastatic infiltration. MRI staged lymphnode-involvement correctly only in 5 pts, while lateralization of In-metastases by MRI was correct in 6 pts. These results suggest, that endoscopy and MRI provide better T-Staging of SCC of head and neck as compared to PET. Howewer, PET yields more accurate determination of lymphnode involvement. PET may be indicated in patients considered for surgical therapy. Recently for this reason a new monoclonal antivody which specially directed against SCC became available. Ten patients with histologically proven SCC were included into the study. Ages ranged from 51 to 73 years. Tatient received 1 mg SQ 174 radiolabelled with i000 to 1600 MBq 99mTc. Data acquisition was performed in planar and SPECT technique 3-4 and 22-25 hrs. after application. RIS was able to detect 8 of the ten primary tumours. One patient had histopathologically proven nodal desease. This lymph node was seen in RIS. No false positive results were seen in RIS wheras Sonography, CT and MRI showed several false positive results. The value of the SUV (= standardized uptake value) of F-18 FDG depends on the timepoint of the determination. We compared the time course of the FDG-Uptake in lymphnode metastases and in primaries. 8 men (51.9 -+ 7.4 a) with SCC of the head and neck were investigated at a SIEMENS ECAT 951 R PET scanner. In the tumour region a transmission scan was done for 20 min. Immediately after i.v. injection of 370 MBq F-18 FDG dynamic emission tomography up to 1 h p.i. was started (6 x 5rain, 3 x 10min). PET images were generated by filtered backprejection to an image matrix of 128 x 128. Furthermore, a correction for attenuation and scatter was done. The spatial resolution was 6.2 mm. ROl's were drawn over at least 2 em large turnouts or lymphnode-metastases and SUV was calculated for each time frame (activity conc. (nCi/g)/inj. activity (nCi)/body weight (g)). The time course of the FDG-Uptake in primaries and lymphnode metastases showed no signifi-no. cant difference. SUV was increasing up to 60 min p.i. without a $ leo. plateau phase. There is no marked difference ~ 8o. in the FDG-Uptake in primaries ~ ~o. and lymph node metastases of 2°~TI has demostrates to have the potential of reflecting accurately viable tumoral burden. A total of 24 patients (7M, 10F), age range: 6/31 years with suspected malignant bone tumors were studied using 2°ITI. 31 studies were performed; 18 of them were done at diagnosis and 13 during the follow up. Ten minutes following intravenous inyection of 2°ITI (74 MBq) multiplanar images were obteined. The uptake ratio of the lesion (L) to the contralateral normal bone (BKG) was calculated in all cases. 2°ITI L/BKG ratio before onset on treatment was between 1.3-4.04 (X= 2.15). Aneurismal bone cyst had L/BKG ratio of 1.63. 2 There was a decrease in L/BKG ratio in most of the patients except in two after chemotherapy not meaning a tumoral necrosis higher than 95%. 3 Seven of the nine patients in which 2°ITI scans performed after chemotherapy who had a L/BKG ratio higher than 1.3 had tumoral necrosis less than 80% verified in the resection specimen. 4 In 3 patients L/BKG ratio was able to differenciate osteoblastic reaccion secondary to surgery from local relapse of the tumor. iThe value of L/BKG ratio before therapy did not correlate with the response to preoperative chemoterapy. 2 There is relatioship between L/BKG ratio and histological tumor necrosis. Tumor with less necrosis had higher ratio. 3 Sequential 2°ITI scanning along preoperative chemotherapy may aid in assesment if the therapy schedule should be maintained or changed until surgery. Castellani MI~ Seregni E, Maffioli L, Gasparini M, Buraggi GL. Nuclear Medicine Dept. -Istituto Nazionale Tumori -Milano -Italia RADIOIMMUNOSCINTIGRAPHY OF BONE MARROW IN LYMPHOMA Bone marrow (BM) biopsy is the main procedure to detect BM infiltration in malignant lymphomas. However, it is an invasive procedure which can be performed only at few skeletal sites, with the risk of false negative findings. Radioimmunoscintigraphy (R/S) with Tc-99m labeled antigranulocyte MAb BW250/183 seems to be efficacy in detecting BM or bone localization in malignant lymphomas, but its specificity is still to be determined. The aim of the present study was to evaluate the usefulness of RIS with MAb BW250/183 labeled with Tc-99m (555-740 MBq), in malignant lymphomas, comparing the results with BM biopsy. RIS was judged positive in case of presence of cold areas. The results in 12 patients are summarised in Table l. In patients with documented BM invasion RIS was positive in 8/8 patients. In 3/4 cases with no documented BM invasion RIS was negative. In a patient heavily pretreated R.IS showed several cold areas although BM negativity. In untreated patients, RIS showed a very good correlation with clinical status. In pre-treated patients the usefulness orRIS is limited because it can be positive in case of both BM infiltration and post therapy fibrosis. Rat prostate adenocarcinoma cells were incubated for 10 or 60 minutes in media with different glucose content. Furthermore, the cells were treated for 4 hours with different doses of gemcitabine and the FDG uptake was measured immediately and 4 hours after the end of treatment. The FDG transport was determined with a zero-trans assay and the mRNA content of the glucose transporter type 1 (GLUT1) and the hexokinase (Hk). After 60 minutes incubation a decrease in FDG uptake was found with increasing cell number in all media. A shorter incubation time of 10 minutes yielded more stable uptake data. The glucose content decreased with increasing cell number and incubation time, indicating that the glucose-to-FDG ratio is not constant in assays using glucosecontaining media. According to these data, we suggest an uptake procedure in glucose-free medium with an end concentration of 0.1 mM FDG or a zero-trans assay to determine the maximum velocity (Vmax) and the affinity (Kin) of the transport system. Treatment with gemeitabine caused a rime and dose dependent increase in FDG uptake. Incubation experiments with 3H-inulin revealed that the changes were not caused by unspecific membrane alterations. The K m of the transport system remained unchanged, whereas Vmax in" creased. However, the mRNA content for GLUT1 and Hk was unchanged. These data indicate that the number of glucose carriers at the plasma membrane increased after treatment with gemcitabine, probably due to redistribution phenomena from intracellular compartments to the plasma membrane. These effects may be part of cellular stress reactions after exposure to chemotherapy with gemeitabine. Drug resistance is a well-known disadvantage in chemotherapeutical cancer treatment. This has not been verified for the anthracycline derivate 4"-deoxy-4"-iododoxorubicin (IDOX). Therefore, this study was designed to evaluate the uptake of radiolabelled IDOX in carcinoma cells with clearly defined drug response, i.e. anthracyline resistant (ARC) and sensitive (ASC). IDOX was radiolabe]led with I-123 in conventional manner by the Iodogen method yielding radiochemical purity of > 98 %. 10 kBq 1-123labelled IDOX and 20 kBq T1-201 were added to each culture medium (n=100), respectively. Cellular uptake was stopped by removing the medium at different incubation times and cooling. After washing, measuring cellular uptake in a well counter, and correcting for physical decay, uptake of I-123-IDOX was calculated in anthracycline resistant (D 257/85 DR) and sensitive (D 257/85 P) human gastric carcinoma cells. Results are given as percental uptake of the activity applied and as well as ratios to the uptake of T1 In conclusion, uptake of IDOX could be shown to be higher in sensitive than in resistant gastric carcinoma cells. The kinetics in ARC suggest a diminished uptake rather than an active transport out of the cells. Thus, IDOX behaves similarly to anthracylines known. Due to the increase of immunoscintigraphy (IS) in infections, turnours and their metastases, the problem of HAMA (human antimouse antibodies) has become more relevant, because HAMA may influence the diagnostic outcome of IS. So the aim of this study was to evaluate the clinical relevance of HAMA in IS using different MAbs. In about 245 patients (mean age: 57 yrs; range: 20 -89) 265 HAMA serum courses were intensively documented up to eight weeks after injection of various and differently labeled monoclonal antibodies: In 197 patients (215 HAMA courses) IS of infections was performed, partially after repeated or simultaneous injections of antigranulocytes MAb [I-123-Mab47 (0.15 rag), Tc-99m-Mab47 (0,4 mg); Tc-99m-BW250/183 (0.4 rag)]. 21 patients (23 courses) with coloreetal cancer received anti-CEA MAb [Tc-99m-BW431/26 (1 mg)], and in 27 patients monoclonal anti-melanoma F(ab') 2 fragments [Tc-99m-TECNEMAB-K-1 (0.35 rag)] were administered. HAMA serum titers were determined by an ELISA-test system. Pathologieaily elevated HAMA serum levels were seen in 40/265 (15 %) courses of all patients examined [antigranuloeytes MAb: 17/165 (11%) after first, and 16/50 (32 %) after repeated injection; finti-CEA MAb: 4/21 (19 %) after first, 2/2 after repeated injection; after anti-melanoma F(ab')2: no pathological response] mostly two and four weeks after application and a normalization eight weeks thereafter in most of the cases. Seven patients of all (about 3 %) with strongly high HAMA tlters after repeated MAb injections showed an altered biodistribution of Mabs and reduced imaging quality, but no adverse reactions. The results show that in IS the potential human immunoreaction (about 11% after first injection) depends on the total MAb protein amount applied, especially after repeated injections. The maximum of the HAMA response, especially in IS of infections, appears two weeks ager injection with a mostly complete regression after 8 weeks. So in routine diagnostic work after first injection of/dAb, the problem of HAMA is negligible regarding potential disorders of the biodistribution of MAb or of the imaging quality of IS as well as adverse reactions. PET images as well as SPECT images are often difficult to evaluate due to uncertainties in the reference to the underlaying anatomical structures. Even the display of orthogonal planes cannot always eliminate the obstacles in the interpretation of images with very high contrast. We studied several cases with high focal uptake in primaries and metastases of breast cancer with FDG-PET, (transmission and emission scans), and with MDP-SPECT (bone scan). The PET-images were acquired on a CTI ECAT Exact scanner with an axial FOV of 16.2 cm. The bone studies were performed with a Picker Prism 3000 triple headed SPECT camera. A multipurpose registration and imaging tool was used, to check the alignment of PET-transmission versus -emission or to match PET-versus SPECT-emission scans. The interactive, retrospective registration process is based on the visual interpretation of multiple views using internal landmarks like bony structures or characteristic areas of increased uptake. Volumetric data sets are generated by linear interpolation for both studies with subsequent application of the so-called integral shading technique. Starting at a surface pixel of the transmission data an optional number of pixels is integrated in the viewing direction. Depending on the integration length, structures within a certain depth can be visualized. This allows an integrated display of transmission and emission scans highlighting areas of focal uptake relative to the surface-rendered body outline. This technique has been extended for use with SPECT data. This approach was appreciated in clinical eases combining multiple aspects of the tomographic studies in a single display. S.Cammilleri*,~.Perdereau*,F.Brixy*,B.Benyahia, J.Y.Pierga*,C.Chypre**,H.Magdelenat*. *Institut Curie -**Cis Bio France TUMOR. Oligonucleotides represent a class of chemicals which pharmaceutical potential has recently been recognized. Key to developing the use of these chemicals as drugs, is the understanding of their biodistribution and metabolic properties. Material and method : Human breast cancer cells (MCF7) in co-culture with human fibroblasts were transplanted in female nude mice (6 weeks later, tumor weight : 0,3±0,1g) . A 22 met phosphodiester oligonucleotide, with a tyramine group in 5' (TON) was 125I labelled (chloramine T) and intratumorally injected (I,036±0,074MBq / ~ 16~g TON). Image recordings were performed by planar scintigraphy. Target organs were removed, weighed, and radioactivity was measured by gamma counter after imaging. R e s u l t s : Images p e r f o r m e d lhr P.I. showed essentially tumor, liver and intestinal uptake ; between 3hr and 6hr P.I., intestinal radioactivity increased whereas liver decreased and 24hr P.I.only the tumor was objectivated. Tumor/normal tissue ratio increased over time. Tumor/muscle Tumor/liver The overall elimination was fast and important (~95% at 24hr) with major h e p a t o d i g e s t i v e pathway (85% fecal, 15% urine). Intratumoral injection of phosphodiester leads to high and i n c r e a s i n g t u m o r / r a t i o and thus offers a potential advantage for therapeutic use. In recent years it has been shown that verapamil increases both intracellular concentration and cytotoxicity of anthracyclines like doxorubicin (DOX) or the new derivative 4-iodo-doxorubicin (IDOX) in resistant tumor cells. However, due to the well-known cardiotoxicity of anthracyclines, there are only few data concerning the impact of verapamil on myocardial accumulation of radiolabelled DOX and IDOX to estimate the potential risk of increasing cardiotoxicity. DOX and IDOX were radioiodinated with 1-123 by the Iodogen method yielding radiochemical purity > 98%. 40 MBq of labelled DOX and IDOX were administered intravenously to four rabbits, respectively. Additionally, 1 mg verapamil was injected i.v. prior to injection of the radiolabelled drug in two animals of each group. Subsequently, whole body sequential scintigrams in 5 rain intervals were taken up to 100 min p.i.. Cardiac accumulation was determined as percental uptake of total body activity. Cardiac accumulation of DOX, DOX + verapamil (DOX+), IDOX and IDOX + verapamil (IDOX+) were decreasing in time in a single exponential manner as shown in the following Antitumour efficacy of anthracyclines in malignant diseases has been proven. However, their numerous side-effects as well as tumour resistance demand research on the development of new analogues. The purpose of this study was to asses the uptake of 1-123 labelled anthracycline derivatives in rabbits, an animal with kinetics similar to man for this antibiotic group (Brenner 1984) . Doxombicin (DOX), 4-Iodo-doxombicin (IDOX) and Dannorubicin (DNR) were radioiodinated by the Iodogen method. Separation was performed by HPLC. Radiochemical purity was higher than 98 % in all cases. Tracer distribution was assessed within a period of 90 minutes by whole body scintigraphy after i.v. application of 10 MBq/kg body weight. Highest uptake was seen for the intestines when used 1-123-DNR (9.5 %) followed by 1-123-IDOX (4.8 %). Iodinated DNR showed a low cardiac uptake (0.8 %) and a high hepatic accumulation ( The state of progression or remission of bone metastases following therapy is currently documented mainly by standard bone scintigraphy or X-ray scans. Both methods can only be employed to a certain extent and therefore are limited as a tool for rapid decision making concerning changes in therapy concepts and/or early evaluation of therapy success or failure. The aim of this study was to estimate the use of the proliferation marker tissue polypeptide antigen specific (TPS) to predict the actual status of known bone metastases as compared to the results of standard Tc-99m-MDP bone scintigraphy. In the learning phase of this study, serum levels of TPS we correlated with the results of bone scans of patients transfered to our department for routine bone scintigraphy. At the first analysis the results of patients with no documented primary tumor (N=10) were correlated with those suffering from cancer (N=70). In a second analysis, patients with a known malignancy were subgrouped depending on the results of the bone scan as follows: 1) no bone metastases detected (N=44); 2) known bone metastases (N=26) a) in remission (N=3), b) stable disease (N=14) and c) progressive disease (N=9) as compared to previous scans. Our preliminary data indicate significant lower TPS serum levels in patients without a known primary tumor as compared to patients suffering from a malignancy. No significant difference was found comparing TPS serum levels of the various subgroups due to high variance. Nevertheless, patients with proven bone metastases (n=9) showed a dependency of TPS levels and extent of disease. On the other hand, scintigraphically documented metastases were never associated with normal TPS levels. We conclude from these preliminary data that TPS is probably not able to replace bone scintigraphy per se, but might allow to follow and supplement bone scans in the individual course of cancer. Physico-chemical properties, e.g. lipophilicity may effect cellular uptake This could be shown successfully for 1-123 versus Tc-99m as radiolabel. Therefore, the aim of this studie is to compare the uptake of two analogous anthracylines being different in an additional iodine only, i.e. doxombicin (DOX) and iodo-doxombicin (IDOX). Both anthracyclines were radiolabelled with I-t23 in a conventional manner by the Iodogen method yielding radiochemical purity of more than 98 %. t0 kBq 1-123-DOX or 1-123-IDOX were added to each culture medium in addition to 20 kBq T1-201 (n=100), respectively. Cellular uptake was stopped by removing the medium at different incubation times and cooling. After washing, measuring cellular uptake in a well counter, and correcting for physical decay, uptake of 1-123-DOX and 1-123-IDOX was calculated in human gastric carcinoma cells (D 257/85 P). [min] 1 10 60 120 240 1 10 60 i20! 240 1-123-. .24 All results in this table are given as medians (n=5 per incubation time) of percental uptake of the activity applied. Observe, both 1-123-DOX and 1-123-IDOX showed approximately 3.4 times and 3.2 times higher uptake than T1-201, respectively. In conclusion, both kinetics and amount of uptake of the more lipophilic I-123-IDOX and I-123-DOX are very similar. Thus, lipohilicity is not a determining factor for cellular uptake. Uptake measurements of radiolabelled anthracyclines may be affected by its different physico-chemical properties due to different radiolabels. This could be shown for 1-123 versus Tc-99m as radiolabel. Therefore, the aim of this study was to compare labelling by adding (I-123) versus labelling by an exchange reaction (C-14). Doxombicine (DOX) was radiolabelled with I-123 in a usual manner by the Iodogen method yielding radiochemical purity of > 98 %. C-14-labelled DOX was purchased from Amersham (Brannschweig). 10 kBq 1-123-DOX or 0.3 kBq C-14-DOX were added to each culture medium in addition to 20 kBq TI-201 (n=110), respectively. Cellular uptake was stopped by removing the medium at different incubation times and cooling. After washing, measuring cellular uptake in a well counter or a beta liquid scintillation counter, and correcting for physical decay, uptake of 1-123-DOX and C-14-DOX was calculated in human gastric carcinoma cells (D 257/85 P). -201 .12 .20 .24 .19 .20 .12 .16 .17 .32 .21 All results in this table are given as medians (n=5 per incubation time of percental uptake of the activity applied. Observe, I-123-DOX showed approximately 4.5 times higher uptake than TI-201 while C-14-DOX showed approximately 18.3 times higher uptake than Tt-201. In conclusion, uptake of the more lipophilic 1-123-DOX is limited by saturation while C-14-DOX showed an almost linear uptake with time. Thus, lipohilicity is not the main factor in determining uptake of radiolabelled DOX. LL2 is an IgG2a murine monoclonal antibody (MAb) directed against the CD22 antigen found on normal and malignant B cells. Clinical studies using LL2 have shown excellent tumor targeting in patients with non-Hodgkin's lymphoma (NHL). Although NHL patients are less prone to develop an anti-mouse antibody response (HAMA), HAMAwill develop after multiple administrations. In order to reduce the risk of HAMA, we have developed a human/mouse chimeric LL2 (cLL2), and have shown that it has identical binding properties to the murine LL2 IgG, as evaluated by RIA and flow cytometry. Three patients with advanced refractory NHL have been studied using 131-I-cLL2 (-2 mg, 8-15 mCi), with 2 of these patients also receiving 131-I-murine LL2 F(ab')2 for comparison. In the 2 patients in whom both cLL2 IgG and murine LL2 F(ab')2 were given, tumor targeting was similar. Increasing the protein dose of the cLL2 IgG from -2 mg to 20 mg in 1 patient with bone marrow involvement decreased the blood clearance rate by 2-fold, and had a variable effect on tumor targeting. These studies suggest that the cLL2 compares favorably to the murine LL2, and thus may be a useful agent for the radioimmunotherapy of MEL. ( The aim of this study was to investigate the behaviour of 99m-Tc Gg4 in different neoplastic pathologies. A total of 169 patients (pts) were studied.The pts were IV injected 555 ~q 99m-Tc ~q~.Increased activity anctrmilation in regsrd to nearby soft tissues were accepted as positive.Quantitative evaluation was also applied by ROIs drawn over lesions and contrlateral site ( L/C ).All pts were examined by other imaging modalities (US,CT,MJLI etc.).Final diagnosis was determined by pathological eyeminatien. The pathological disgnosis and 99m-Tc G~4 findings of 169 pts are as follows: l)Turors of mesanchvmal origin: 33 malignant (2.6 + 0.8) and 7 benign (0.9 + 0.I) tutors (tam) originsted from connective and endothelial tissue were included (p 0.005).12 malignant lymphomas originated from lymphoid tissue did not show any (+) GS~H aentmulation. 2)Tomors of epithelial origin: 41 nmlignsnt melsuoma metastases originsted from neuroectodermal origin were well visualised (1.84 + 0.2). 21 epidermoid carcinomas (Ca) (2.1 + 0.24) and 1 papilloma (negative uptedfe) originated from stratified squamoas tissue were also included. 3)Miscelleneous: Plecmorphie adenoma (4 pts), thyroid follicular adenoma (3 pts), benign lympadenitis (2 pts), breast tins (12 pts), gynecologic tms (12 pts) did'nt show any GSH uptake.Moreover, neural crest tma (15 pts) with (+) 1-131 MIgG aentmulation did'nt demonstrate any GSH uptake. 6 pts with other miscellenous tins were also (-) with 99n-Tc GSH. As a conclusion;l) 99m-Tc GSH nay not simply a blood pool agent, 2)Active transport may be the dominant med~mism that is responsible for GS[[ transport into the intracellular compartrent and 3) tins originated from connective and endothelial tissues of mesenshymal origin, tins originated from stratified squsmoua epithelium of epithelial origin mad fiaslly tins from ne~roectoderm origin (nevus and maJignsnt melanoma) sho~ed positive 99m-Tc GSH uptake.Therefore, 99m-Tc GSH may be a promising agent in differentiation of benign and malignant lesions and in detection of metastases and recurrences of these groups of tumors. It has been shown in animal and metabolic studies that Tc-99m sestamibi does not accumulate in necrotic myocardial tissue despite nomlal blood flow. If. similarly, Tc-99m sestamibi does not accumulate in ncerotic tumor tissue, then, it could be used in follow-up of patients with malignant tumors after radiotherapy, which induces tumor necrosis. The aim of this study was, therefore, to assess the effect of tumor necrosis on Tc-99m scstamibi uptake. Thirty eight patients with 4 major types of bronchial carcinoma were included in this study. Planar (n=38) and SPECT imaging (n=29) was initiated 10-15 minutes after the injection of 370-740 MBq Tc-99m sestanlibi. Tumor necrosis was diagnosed in 12 patients based upon histopathology (n=2), and density measurements and type of contrast cnhancemcnt on CT scan (n=8). Of the patients, 34 showed Tc-99m sestamibi tumor uptake on planar and 27 on SPECT images. Four types of tumor uptake pattern was identified: focal uptake (n=25), focal uptake with a central hypocative focus (n=7), ring-like uptake (n=2), and no uptake (negative uptake) (n=4) on planar images. The corresponding results for SPECT imaging were 17, 7, 3 and 2, respectively. Of the patients with tumor necrosis, 92% (11/12) revealed defective tumor uptake (focal uptake with a central hypoactive focus,n=7, ring-like uptake,n=2, and no tumor uptake, n=2) on planar and 100% (12/12) on SPECT images (focal uptake with a central hypoactive focus,n=7, ringlike uptake,n=3, and no uptake, n=2). In conclusion~ this study shows that Te-99m sestamibi does not accumulate in necrotic tumor tissue. This has significant clinical implications that Tc-99m sestamibi, particularly with SPECT imaging, has a potential role in follow-up of patients with bronchial carcinoma by differentiating recurrent or residual disease from post-therapy necrosis, and in monitoring the response of tumors to radiotherapy. There were 3 equivocal cases on 2°iTi and 4 on 67Ga scintigraphy. Tm/Bkg ratios for positive 2°iTi were ~2. In conclusion, 2°~TI scintigraphy is more sensitive than 67Ga in evaluation of pts with LGL, although this modality detected only 37.5% of the lesions seen on CT. In order to evaluate the use of immunoscintigraphy in uveal melanoma, both for the detection of the primary lesion and of liver metastasis, we performed this methodology in 23 patients (pts), 12 females and 11 males, with a =57+17 years (7-78 years). Three of these pts had been enucleated, 1 had had tumor resection and 2 had benign lesions. The remaining 17 pts had uveal melanoma with an =8.71+4.9 mm (1.5-19.9 mm), measured by echography. Twelve of these pts had also been submitted to CT and/or NM1L The immunoscintigraphy was performed with fragments of the MoAb 225.28S labeled with 99mTc, using 0.35 mg and 750+186 MBq/pt. All-body imaging (10 min./m), planar images of the head, in anterior view, and in 20 pts SPET study (40 seconds/view x 32 views, -90 ° to 90 °) were performed at 4.75_+0.75 hours. At 24 hours post injection, planar images of the head were also done. The first planar head images permitted a 10:17 (58.8%) true positive (TP) results and 5:6 (83%) of true negative (TN) studies. The same results were, respectively, 15:17 (88.2%) and 6:6(100%) for the 24-hour image, and 15:15 (100%) and 5:5 (100%) for the SPET study. Evaluated as a whole group, the~ immunoscintigraphy permitted 16:17 (94%) TP studies and 5:6 (83%) TN ones. The intensity of activity was qualitatively classified as small, moderate and intense, and we tried to correlate it with the biggest diameter of the lesion. It seemed that a biggest diameter permitted a higher focal activity, although the small number of studies in each group did not permit the use of statistical tests. Five lesions were not detected by CT and 3 by NMR, and all of these were visualized with the scintigraphic study. Two pts had liver metastasis, not seen with the 99mTc-MoAb. These results suggest that this method may still be used to study intra-ocular lesions suspected of being melanomic, especially if SPET acquisition is used. On the contrary, it is of no use to detect metastasis, since the main place of secondary lesions is the liver, an organ with a very high unspecific binding of the MoAb. The actual value ofI-123-MIBG SPET in neuroendocrine tumors, and in particular in neurohlastoma (/fiB), is controversial. Therefore a comparison between planar and SPET imaging in NB was undertaken. We report here the resahts obtained in 18 patients (9 M and 9 F, aged 4 m o . -l l yr; one at stage I~ six at stage ]]I, ten at stage IV, one at stage IVS). Imaging (a total of 28 studies) was performed at diagnosis (2), at~er surgery (5), during or after chemotherapy (13), at follow up (5) and at relapse (3). Both planar, at 24 and occasionally 40 Jars (multiple anterior and posterior images; 500,000-1,000,000 counts per scan) and SPET imaging at 24 hrs (64 projections obtained over 360 at 30 sec/projection) were carried out aider i.v. injection of 148-296 MBq of I-123-MIBG. Planar studies gave a sensitivity of 89.5 % and a specificity of 88.9 %. In the same patients SPET gave a sensitivity of 94.7 % and an equal (88.9 %) specificity. When compared with planar scanning, SPET imaging showed a total of six additional pathological areas of uptake in three patients. In another patient an equivocal abnormality on planar imaging was confirmed as pathological by SPET. Furthermore, SPET improved the anatomical assessment of the lesions in 12/18 studies. In conclusion: the association of SPET can improve the diagnostic efficacy of MIBG scintigraphy in the evaluation of NB. In our experience SPET was conclusive in detecting lesions in one case, essential in another three cases and helpful, by giving additional information~ in 12/18 true positive studies. Westlin JE,Walind S,Lilja A,Ahlstr~m H, L~ngstr6m B. The PET-centre, Uppsala University, S-751 85 Uppsala, Sweden Thirtysix consecutive patients admitted for llC-methionine PET were investigated. All p a t i e n t s w e r e a d m i t t e d for p r i m a r y investigation before therapy. The patients were examined with a whole body PET camera, GE 4096 (General Electric medical systems), which produces 15 simultaneous c o n t i g u o u s axial slices with a thickness of 6.5 mm and a resolution of 5-6 mm.All patients fasted for at least 5 hours before scanning.An activity of 800 MBq L -m e t h y l -l l C -m e t h i o n i n e was administered as an i.v. bolus injection and a scanning for 50 minutes with increasing frame times was performed. In the SUV images regions of interest (ROI:s) covering the lung without hilar vessels were drawn. The ROI:s in the cerebellum covered the whole cerebellum. In 36 patients 44 observations were recorded. The mean SUV uptake value was 0,59 for lung (range 0,343-0,922) SD 0,14. No correlation to plasma methionine or to diagnosis was seen. The cerebellar uptake was 1,39 (range 0,78 -1,85) , SD 0,34. There was a correlation between high SUV in the lungs and a high SUV in the cerebellum ( 0,76).There are great differences between patients in the normal uptake of ll-C-methionine in both the lungs and the cerebellum. mTc. SPET of chest or abdomen was performed at 5-8 horns after injection in all patients. No adverse reactions were observed in any patient after MAb infusion and no appreciable change were seen in the blood counts, renal and liver function tests. A total of 17 from 18 (94.4%) lymphoma lesions were detected by RAID All the tumor locaiizations were confirmed with clinical examination and with other imaging techniques, such as CT scan or MR] or gallium scan In this series of patients no false positive results were noted and only I false negative result in a patient who had a mediastinal bulky disease. As regard the biodistribution of the immunoreagent we can do the following considerations :-) no appreciable marrow activity was seen in all patients -) spleenic targeting was demonstrated in all patients -) tumor to non tumor ratio ranged from 12 to 2.8 -) no difference of uptake was noted in different tumor grade The images performed 24 hours after injection did not detect new lesions, but areas of doubful uptake were seen as positive focal areas in the delayed scan In these preliminary results the LL2-Fab MAb seems to be useful for detection staging and follow up oFNHL patients. The application of Tc-99m-MIBI instead of TI-201 seems to be desirable because of a lower radiation exposure, a more favourable distribution and better image quality. Therefore we examined 17/117 patients with OTC suspecting recurrent disease after thyroidectomy. Planar imaging of the whole bochr was performed 15-20 min. after admainistration of 74 MBq TI-201 and 555 MBq Tc-9Sm-MIBI. In addition all patients had a SPECT study of the neck and chest after planar imaging. 10/13 local recurreneies (LR) were detected planar with b e t h radiopharmaeeuticals (R). In one ease the tremor was Te-99m-MIBl-pesitive and TI-201negativ. 2 LR could not be demonstrated neither b y TI-201 nor by Tc-99m-MIBI scintigraphy. In case of distant metastases planar scintigraphy with both R led to the tumor site (n = 9). Moreover 6 recurrent free patients as well as two patients with abnormal Tg-ser~-levels had a normal scintigraphy. That means: Tc-99m-MIBI true positive (TP) 20, false negative (FN) 4, true negative (TN) 6 and false positive (FP) 0; Ti-201 TP 19, FN 5, TN 6 and FP O. SPECT was proved to be important for localisation of recurrent disease. Tumors in addition were not deteetable. Quantification of the tumor uptake of TI-201 and Tc-99m-MIBI using the l{OI-methed led to a higher tumorhaekground-ratio for Tc-99m-MIBI. The difference was proved %0 be highly significant (p _< 0.0005). TC-99m-MIBI planar imaging as well as SPECT showed a higher imaging quality compared to TI-201, especially in deeply situated tremor lesions. In conclusion, Tc-99m-MIBI seems to be a promising alternative imaging agent in the follow-up of oxyphilio thyroid carcinomas. DOSE RATE MEASUREMENT AND TARGETED RADIOTHERAPY WITH 186RHEN1UM_HEDP FOR THE TREATMENT OF PAINFUL BONE METASTASES. We have treated 21 patients with disseminated painful bone metastases with 186Re-HEDP. Patients received 40 mCi of 186Re-HEDP with iterative readministration 3 to 4 months later in cases of a favourable antalgic response and after hematopoietic toxicity has subsided. Rhenium-186 emits both beta and gamma rays. The beta emission provides the local irradiation of metastatic lesions while the gamma emission enables visualization of the tracer's biodistribution and dosimetric calculation. In all cases, conjugated view sequential whole body scintigraphy allows to calculate a cumulated activity curve. Knowledge of the physical characteristics of Rhenium-186 and of the accurate volume of a painful metastasic site (by tomodensitometry) associated with the activity curve allow dosimetric calculations to establish the dose rate and the total dose to the reference metastasis. To appreciate the efficacy and toxicity of targeted radiotherapy, we also measure pain score, analgesic index and various biological parameters. Analysis of these parameters suggest a correlation between the calculated dose rate and clinical and biological responses. We observe no favourable clinical response with dose rate under 0.2 Gy/hour whereas dose rate over 0.5 Gy/hour are often associated with complete antalgic responses. This efficient dose rate, if not reached by the first administration, could be approached by the iterative administration of the radiopharmaceutical. An effective treatment increases the osteoblastic activity in the metastatic lesions which could increase the later uptake of the radiopharmaceutical, the dose rate and therefore progressively ameliorate the antalgic efficacy of the treatment. In a prospective study, we evaluated the efficacy of Re-186 HEDP for the reduction of pain and consequently, the need for analgesics in patients with skeletal metastases. 20 single injections of 1295 MBq were given to 18 patients (prostate cancer n = 10, breast cancer n =5, lung cancer n=l, bladder cancer n=l, colorectal cancer=l) who received analgesics for the treatment of pain caused by multiple bone metastases (solitary metast, n=2). Tc-99m MDP bone scans (obtained before therapy) and Re-186 HEDP scans were used for quantitative analysis. The mean Re-186 HEDP uptake in the skeleton was 19% of the injected dose. The average uptake in the bone metastases was found to be 3.1%. There was a high correlation (r=0.92) between the metastasis/normal bone-ratios of the Tc-99m MDP bone scans and the Re-186 HEDP scans. In two patients, we gave a second injection of Re-186 HEDP. There was no significant decrease in the mean Re-186 HEDP uptake after the second injection. After 1-2 weeks, 4 patients reported complete pain relief. A significant or slight reduction of pain was reported by 9 and 4 patients, respectively. In 4 cases there was no more need for analgesics after treatment with Re-186. 8 patients showed a marked decrease in the need for analgesics. The maximum interval of pain relief was 3 months. Half of the patients showed a reversible thrombopenia, in 2 cases we found a slight leukopenia. A flare reaction was reported by 7 patients 12-24 hours after the injection. We conclude that Re-186 HEDP uptake can be predicted by a Tc-99m MDP bone scan before therapy. Therapeutical application of Re-186 HEDP results in a significant relief of pain and decrease in the need for analgesics in patients with multiple bone metastases for a period of up to 3 months. No severe side effects could be observed. Thirteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics, and who were not eligible for or had not responded to local field radiotherapy, were treated with Sr-89. All patients had previous treatment with chemotherapy and radiotherapy for bone metastases. White cell count was >3x109/L and platelet count was > 100xl09/L. Twelve patients had > 20 bone lesions in the bone scan and 1 patient had 5 lesions. The time of evolution since the diagnosis of skeletal metastases had been made was 63+39 months, range 22 to 135. Severity of bone pain, mobility and dependency on analgesics were evaluated before, 4, 8 and 12 weeks after Sr-89 administration. Patients received 2MBq/Kg (120-150 MBq) of Sr-89 by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 6 of 13 (46%) patients 4 to 8 weeks after treatment: substantial improvement was observed in 2 patients and some improvement in 4 patients. Duration of the response oscillated from 3 to 7 months. Seven patients did not respond to Sr-89 administration. A decrease in peripheral blood cell count was observed in 10 patients: a 15-66% reduction in white cell count and a 14-75% reduction in platelet count was detected at 12 weeks after treatment in these patients. We conclude that strontium-89 is useful for bone pain palliation in bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain. The efficacy and toxicity of treatment with 1400+100 MBq of Re-186-HEDP [Maliinckrodt Medical B.V., Petten] were investigated in 27 patients who suffered from metastatic prostate, breast, bladder and colon cancer. The foUow-up period was thirty weeks. The efficacy of the treatment was assessed by (a) a pain and performance questionnaire that the patients were asked to complete daily and (b) a CT scan comparison of a randomly preselected osseous lesion before and 30 weeks after Re-186-HEDP i.v. application. The response to treatment was also evaluated by using the Karnofsky Index. Ten out of 12 patients with prostate cancer, 7 out of 9 with breast cancer, 2 out of 4 with bladder cancer and 1 out of 2 patients with colon cancer responded to therapy. Four patients became free of pain, 16 experienced obvious and 2 some improvement. No change was observed in 5 patients. Thirteen patients manifested a flare response to treatment, with increase in pain within the first 10 days after Re-186-HEDP administration. All patients showed a definite and 6 of them a clinically important decrease of platelets and absolute number of polymorphonuclear white blood cells up to the fourth week following treatment. Three patients underwent a whole blood transfusion and in two of them neurologic side effects were observed lasting about 10 days. On CT scan comparison of the secondary osseous lesions an histopathologic improvement was noticed. Re-186-HEDP appears to be a promissing new metal ion complex for the palliation of painful bone metastases, particularly in prostate and breast cancer. Aim of this study was to yield data about floor contamination following radioiodine treatment at a nuclear medicine therapy unit. Between 1990 and 1992, measurement of floor contamination was done in a nuclear medicine unit comprising six beds with 350 days running time per year by monitoring the floors three times a week with a xenon gas-chamber detector. During the three year observation period, 649 patients were treated with a total dose of 1147 GBq (31 Ci) 1-131. A value of > 0.5 Bq/cm 2 was classified as "contamination". Overall, 108 contaminations were detected, 94 (87%) of them in the patients' rooms and t4 (13%) in the remaining rooms, all of the latter sharing values below 5 Bq/cm 2. Classified by levels of contamination, 55 (51%) were in the range between 0.5 and 5, 37 (43%) between 5 and 50 and 16 (15%) > 50 Bq/cm 2, In conclusion, contaminations > 50 Bqlcm 2 (borderline for appropiate actions according to the German radiation safety order) occurred with a frequency of 16 events of 5250 bed-days (0.3%) and, therefore, represent a rare event. In-ll4m were found to give such complexes in citrate medium and have ideal therapeutic radionuclide properties. Three patients were chosen for Y-90 therapy and two for In-ll4m therapy. Initial dose of the radionuclide administered i.v. was Iii MBq for Y-90 and 74 MBq for In-ll4m. Both radionuslides concentrated intensely and bound strongly to the primary and secondary cancer. Due to short half-life of Y-90, patients needed readministration of the radiopharmaceutical first at weekly and then at longer intervals for being free from bone pain. A single dose of In-ll4m on the other hand was found to keep the patient without pain for more than 3 months. Due to longer half-life, however, patients developed easily platelet depression. We are trying to overcome this disadvantage of In-ll4m radiopharmaceutical. Lung cancer volume shrinked in patients of both groups. The patients are followed up with bone and Ga-67 total-body sointigraphy. We have also observed complete remission of advanced lung cancer with cationic Pt(II) complex in patients kept on special diet; Radionuclide cancer therapy has so far been limited to bone metastasis pain palliation with Sm-153-EDTMP, Re-186-HEDP, Sr-89-C12, NaOrthophosphate-32 or Y-90 citrate solutions. Present paper reports the cure of 19 patients with tumour-affine Y-90 solution. The biochemical properties of prostate cancer and its metastases investigated with pure radionuclide (To-99m, Ca-67, Sm-153, and Y-90) distribution in prostate cancer patients showed that prostate cancer is cation-affine while its bone metastases have high affinity for radionuclide anionic species. Studies of the complexes formed by Y-90 with citrate, EDTA, or DTPA as ligands showed citrate medium to be most suitable to obtain both cationic and anionic complexes of Y-90 for advanced prostate cancer therapy. Ninteen patients with widely diffused bone metastasis, with PSA value above 250 ng/ml and in whom surgery, radiotherapy and hormone therapy had failed to arrest the growth of the disease were admitted to this Y-90 therapy. Depending on the seriousness of the disease, first dose given i.v. to the patient has been iii MBq. Subsequent doses were 74 MBq each week until the bone pain disappeared, PSA value returned to normal, and bone scintigrame shewed no metastases. PSA value, bone seintigraphy, and blood analyses of the patients were examined first at 3 months interval and then half-yearly. No adverse effect of the therapy was so far observed. Patients resumed their normal activity. Follow-up time so far has been 2 years. In the course of radioiodine treatment of hyperthyroidism, 1-131, a beta emitter with a mean range in soft tissue of 0.5 mm, possibly may damage C-cells by irradiation which originates from neighboring follicular cells. Up to now, only few retrospective studies have focused on this question. We therefore started a prospective study in 15 patients with Graves" disease and 15 patients with functional autonomy. Plasma samples for the determination of calcitonin were drawn immediately before and 6 weeks after 1-131 treatment. Since plasma calcitonin is undetectable in more than 50% of healthy persons, a solid phase silica gel extraction method was used to enrich monomeric calcitonin (mCT) in plasma. Afterwards mCT was measured by an immunoradiometric assay (CT-IRMA Medgenix). The extraction procedure allowed to measure plasma mCT in all the patients studied, Comparing mCT levels before and after 1-131 treatment, a significant decrease from 6.3 pg/ml to 4.4 pg/ml could be observed in patients with Graves" disease (P<0.05). However, in patients with functional autonomy, initial mCT levels were lower (3.8 pg/ml) as compared to Graves" patients; no significant decrease could be observed after 1-131 treatment (3.4 pg/ml). The decrease of plasma taCT in Graves" patients after 1-131 may be interpreted as radiation induced impairment of thyroidal C-cells. On the other hand, since this effect is not seen in patients with functional autonomy, initially higher levels of plasma mCT in Graves" disease may be disease specific in the meaning of a more relevant impairment of bone metabolism. OPTIMAL COLLIMATOR CHOICE FOR COMBINED Tc-99m/1-123 STUDIES Dual isotope studies with Tc-99m and 1-123 may be useful for various organs, including brain and myocardium. For images obtained with each of the tracers to be comparable, it is important that activity ratios (activity in one part of the image / reference activity in the image) would be preserved by the imaging method. Therefore, we have used a Rollo phantom to study how collimator functbn affects such ratios. All investigations were performed with 1-123(p,2n), A Siemens Orbiter 3700 camera was used with either a HR or a ME collimator. With the ME used as a reference, the relative efficiency of the HR for Tc-g9m, as measured with a point source, was 71.9%, and that for 1-123, 133,4%. This difference may be attributed to septal penetration. FWHM (ram) measured with a point source were : distance source-collimator (air) HR 1-123 HRTc-99m ME 1-123 METc-9gm 0 em 5.1 5.7 5.2 4.5 8cm 7.6 7.6 10.4 10.0 To investigate quantitative accuracy of planar images, 128"128 images were acquired of a Rolls phantom, filled with an aqueous solution of either 234 MBq Tc-99m, or 292 MBq 1-123, and placed on the collimator surface with 8 cm of plexi interposed. Pulse height windows were: for Tc-99m, 15% around 140 keV, and 20% around 95 keV (scatter); for 1-123, 15% around 159 keV, and 15% around 120 keV (scatter). Activities were measured in ROIs corresponding to the cells of the phantom, and normalised to the maximum in the image. For Tc-99m, regardless of the collimator used, the ratios fairly well approximated the theoretical ones, based on the dimensions of the cells of the phantom. No further improvement was obtained by Jaszczak scatter correction with k = .35. For 1-123, the ratios obtained when the HR was used were consistently higher than the theoretical ones.The ME minimized the differences between the measured and the theoretical values. For 1-123 and the HR, activity ratios were recalculated after the images were corrected for scatter using various values for k. On the assumption that septal penetration and scatter might induce a nonstruetured homogeneous background, we also performed homogenous background subtraction on the images using various threshold levels. All these methods, however, introduced further errors. We conclude that for combined Tc-99m/I-123 studies ME is optimal, because of its higher quantitative accuracy. Spatial resolution, although less than for HR, remains similar for both tracers when the ME is used. with LM from DTC submitted to 131I therapy. We observed 90 patients (pts) (30 follicular, 38 papillary and 22 mixed-24 males 66 females -mean age 48.1 ± 18.1 years). Generally methastases were detected within one year from surgery, but in 21 cases this occured later (range 3-15 years). From the time of detection, we calculated survival curves dividing patients by age, sex, histology and 131I uptake~ then we compared obtained results at 5, 10, 15 yrs intervals. Survival curve by age, under or over 45, shows a statistically significant longer extention of life for pts under 45 (Student two tailed t-test:p 50% Quantification of neovascularization due to angiogenic factors like interleukines is difficult when only using histological techniques. However, the evaluation of tissue perfusion is a classical task of nuclear medicine. In this study the washout of Xenon-133 as an established indicator for blood flow was applied to evaluate angiogenesis quantitatively. Two polyester foam sponges containing either interleukin 8 (IL-8) as angiogenic factor or placebo were implanted subcutaneously in the back of 5 rats. After 4, 9, 13, 20, and 40 days 0.1 ml Xe-133 gas with a mean activity of 1 MBq was injected first into the IL-8 sponge and 3 hours later after complete Xenon washout into the placebo sponge of the same rat. Immediately after injection the radioactivity of the sponge region was measured up to 20 rain p.i. in 1 rain intervals using a collimated gamma-scintillation detector. Washout data of Xe-133 are given in percent of injected activity. Subsequently, the sponges were dissected and examined histologically. In the following table only washout data of Xe-113 on day 13 are given as an example for IL-8 induced angioproliferation between day 4 and 20: time p.i. 16.7% 13.2% 39.6% 26.1% The corresponding half-life periods of Xe-133 washout on day 13 due to exponential curve fitting were 17.3 min and 34.7 min for IL-8 and placebo, respectively. Histological data confirmed increased neovascularization in IL-8 sponges compared to placebo. Thus, measurement of Xe-133 washout seems to be a valid and easy-to-perform technique for quantitative evaluation of pharmacological effects of angiogenic factors in experimental models. Basic studies of 169yb uptake in normal (V 79/4) and KTCTL-2 cells(Heidelberg) were started with the aim of understanding and increasing accumulation of radiometals in tumours.Cellular uptake of 169yb given as citrate or NTA complex is linearly dependent on tracer concentration and incubation time, but is independent of the cell density per petri dish. 169yb uptake is dependent on the metabolic activity of the cell line (checked by [18F]FDG) as well as on the ligand species: the stronger-metabolizing V79 cells take up more 169yb from the citrate complex than the weaker-metabolizing tumour cells, whereas from the NTA,EDTA, and DTPA complexes the uptake is higher by the tumour cells, which does not correlate with the metabolic activities. By both cell lines by one order more 169yb is taken up from the citrate complex than from the aminocarbonic acid complexes. The results suggest the existence of different transport or uptake mechanisms i.)by the fibroblasts (V79/4) and the tumour cells, and ii.) from the citrate complex on the one hand and the NTA,EDTA,and DTPA complexes on the other. They show further that Yb citrate has no specific tumour affinity. The aim of the study was to examine the contamination of the environment from patients during and after radiotherapy.with 1-131 by measuring'the excretion ot activity in-sweat and saliva. For analysing t~e time-course of activity, sweat data from 8 different fixed parts of the body were derived and also from samples of saliva. From patients suffering from hyperthyrodism (HYP) or thyroid cancer (TC) sweat ac~vity was col!6cted_by plasters utihzing a cotton layer, bativa was sampten atter Hnsening the mouth. In sahva a 1-131 content up to 1 M b q / m l (2.7 10 . 4 / m l of the applied activity) was measured during the first day after th4rapy in TC-Patients Differences in I-I31 excretion between TC-and the HYP-patients is given in table 1. The results show that h3~perthyroid patients excret a higher relative amount of activity m the early phase of their treatment via saliva. Conclusion: A relative higher risk to contaminate the environment and a relative higher exposure of the salivary glands can be assumed. Before discharge, however, most of the rest activity is stored in the thyroid in this patients and thus is not available for excretion by saliva or sweat (see table 1). MAb-170 (Tru-Scint®AD TM, Biomira Inc.) is a murine monoclonal antibody (IgG1 Subclass) and was derived from the immunisation of mice with synthetic TF antigen. It was selected on the basis of in-vitro reactivity with h u m a n adenocarcinoma tissue. The antibody was supplied as a single vial, frozen liquid formulation. Radiolabelling was achieved with the addition of sodium pertechnetate (1600 -1800 MBq) to directly label the reduced thio-groups of the antibody. Pharmacokinetic analysis was performed on a subset of breast cancer patients imaged as part of a Phase II clinical trial at the Cross Cancer Institute in order to evaluate the effect of dosage. Either 1, 2, or 4 mg of radiolabelled antibody was administered. Serum, urine and serial whole body images were collected at defined time points and used to obtain a kinetic model to describe the in-vivo distribution of the MAb. The data were best described by a two compartment model of the form: C(t) = Cle -Mt + Cze 4.zt. The pooled distribution half-lives were 4.3 + 1.8 h and the pooled terminal elimination half-lives were 36.9 + 6.2 h. No significant difference was found between the different doses. The radiation dose to target organs was calculated from the cumulated activity in selected source organs as defined by conjugate view g a m m a camera images. Standard MIRD formulae were used to calculate the absorbed dose. In conjunction with frozen section microautoradiography, computer image analysis methods were applied to the analysis and quantitation of In-lll-oxine labelled leukocyte sections and superimposed autoradiographs. Rapid cell fractionation was used to confirm the results. Results: The emulsion (Ilford K2) response was linear over the concentration range investigated (0-53 MBq ml-i). Resolution of radionuclide distribution was better than 2 pm. The autoradiographs showed no dependance of radiolabel uptake on cell type. Classification of all cells into intervals according to grain density suggests an exponential rather than normal distribution, with approximately 50% of cells having little or no radiolabel. In any one sample, cells which were heavily labeled were approximately i0 times more likely to be found in aggregates (60% found in aggregates, mostly neutrophils) than cells which were not heavily labeled (6% found in aggregates); and the grain densities were at least twofold higher over nuclei than over cytoplasm. The last observation was confirmed by the rapid cell fractionation method which showed that approximately 57% of the total radioactivity was bound to nuclei. Frozen section microautoradiography is a practical and reliable approach to determining subcellular distribution of In-lll. The radiolabeling process (not the isolation process) causes aggregation of neutrophils. Uptake is not significantly dependant on cell type, but only a fraction of cells are appreciably labeled. The radioactive concentration in cell nuclei is at least two-fold higher than in cytoplasm. Relevant data concerning the absorption of erbium (Er) from the gastrointestinal tract in humans is hardly available. The dosimetrie tables in the ICRP-30 and ICRP-61 documents are based on the more extensively studied lanthanide cerium. For a clinical study, we performed dual isotope gastric emptying studies, using a post-production neutron activated 170Er enriched erbium-oxide enteric coated pancreatic enzyme preparation. The erbium was available as Er203. Four hours and eight hours after the ingestion of 4 MBq 171Er we obtained whole body scans using a dual headed camera at a scanspeed of 10 era/rain and a high energy collimator. Because of the pH-sensitive enteric coat of the pancreatic enzyme preparation that regulates the release of the pancreatic enzymes and 170Er enriched erbium-oxide, uptake of 171 Er from the gastrointestinal tract was only possible after the gastrointestinal pH exceeded 5.5 which is likely to happen in the small intestine. The preparation also contained significant amounts of 24Na, up to 400 kBq, resulting in increased background levels due to collimator septum penetration and down-scatter effects. Preliminary data from whole body scans in five volunteers indicate that the fractional uptake from the gastrointestinal tract did not exceed 0.0003, which matches the assumptions made in ICRP-30. Except from the gastrointestinal tract no specific uptake was seen in any organ system, especially not in the skeleton, liver or kidneys, as was previously reported by other investigators in animals. However, this may partially be due to the high level of 24Na downscatter. Our preliminary results confirm the assumptions used in the ICRP-30 tables. Further work on 24Na downscatter correction is required. The method of S. Shiomi et al. is an excellent non-invasive method to prove and evaluate the grade of portosystemic shunt. PS index (PSI) may, however, he considerably discorected in three ways. a) The heart ROI in patients with normal or close to normal portal circulation can be marked with lower degree of accuracy owing to the small number of counts in the heart area. b) The liver ROI in patients with serious portosystemic shunts can be marked with lower degree of accuracy owing to the same reason. c) The emission of 99mTc pertechnetate rectal activity in patients with hepatomegaly or in patients with short abdomen may influence considerably the activity of liver ROI. Our modified method solves these problems by following way: The basic five minutes dynamic portal scintigraphy after 800 MBq 99m T c pertechnetate per rectum continues up to ten minutes when 80 MBq of 99~Tc sulphur colloid is administered i. v. on the start of 6th minute. The radioactive bolus in the heart and radiocolloid accumulated in the liver enable to delineate both the heart and liver ROIs by sufficient accuracy. The final static liver/kidney scintigraphy offers to obtain additional valuable informations. The border of rectal (bowel) activity is marked as the first ROI followed by ROIs of heart and liver. The case of interference the bowel and liver ROIs is solved using our own computer programme. The method has been tested on more than 100patients. The normal PSI was up to 7. The span of PSI in patients with liver diseases was from 9 up to 91. Hospitals usually need to document the excreted activity from patients to the sewerage system. Within the United Kingdom, Her Majesty's Inspectorate of Pollution have issued guidelines which are deliberately pessimistic eg. for all long-lived radionuclides the excreted activity is assumed to be 100% of the administered activity, except 131I outpatient therapy and 32P therapy, where the figure is 30%. All 99mTc radionuclides are assumed to be 30% However, in order to assess the mdiological impact of patient excretions, it is important that a more appropriate model of the situation should be used. Most excretions can be expressed as a sum of exponential components. We have derived a model for excretion for a single exponential component. In ICRP53, the whole body loss is generally expressed as a sum of exponential components with appropriate coefficients. These values have been used in conjunction with our model to derive the total excreted activity for a range of radiopharmaceuticals. For long half-life radionuclides, we have shown that the excretion for an exponential component with activity A at time t = 0 is A.T½B/T½ E where T½ B is the biological loss half-life, T½ E is the effective loss half-life. For 99mTc, the aspect of discontinuous bladder excretion can be taken into account and ICRP 53 assume a 3½ hour voiding time. Since only 6% of 99mTe remains after 24 hours of physical decay, excretions were derived for 7 urinary voids. These models will be derived and explained. Using this, a comprehensive table has been collated and will be presented, but in particular the levels for some common long-lived, radionuclides are 131I (thyrotoxicosis) : 60 %, 32P : 43 %, 67Ga : 78 %, and 201Tl : 20 %. Radiosyntheals and evaluation of [nC]-brofaromine, a potential tracer for measuring MAO-A activity with PET Brofaromine [4-(5-methoxy-7-bromobenzofuranyl)-2-piperidine. HC1] is a potent, selective and reversible inhibitor of monoamine oxidase A (MAO-A) and its inhibition is also known to be tissue and time dependent. Two different methods for the labelling of [nC]-brofaromine were applied. The one step method at low carrier concentration consisted of a direct [nc]-methylation of the desmethyl precursor with [nc]-CH3I in DMSO at 80"C for 5 rain. After separation of the N-methylated side product (RP-18, Bondclone, MeCN/0.1% H3PO4 = 31 : 69 %) 30 % yield of [llC]-brofaromine was obtained (EOB and decay corrected). The three step route with high carrier amounts of CO2 consisted of protection of the secondary amino functionality with the t-BOC-group, O-methylation with [nC]-CH3I in DMF at 80"C for 5 min and deprotection of the t-BOC-group (TFA) resulting in a total yield of 10 % (from EOB and decay corrected). Radiochemical purity of [ttC]-brofaromine in both cases was > 98 %. PET studies using [nC]-brofaromine in a rhesus monkey demonstrated a slow accumulation of radioactivity in the brain. In a follow-up experiment, the monkey was given 2 doses of 2 mg./kg p.o. of the selective irreversible MAO-A inhibitor clorgyline 19.5 hours and 7 hours before injection of [11C]-brofaromine. No decrease in radioactivity uptake in the monkey brain was observed. These results indicate either a high degree of non-specific binding or a slow pharmacokinetic of MAO-A inhibition by nC-brofaromine as known from the literature. The available time frame of PET measurements with tiC is probably too short to clarify this question. In conclusion, we therefore propose the use of [76Br] (half-life=16h) as a suitable PET radionuclide. Organic compounds labelled with 14C are used in different "breath tests". The expired metabolic end-product Z4C02 is usually measured by liquid scintillation counting (LSC). Due to the long T~ (5730 years) very few of the 14Catoms present distintegrate during measurement. With mass spectrometry (MS) it is theoretically possible to measure all 14Catoms present.Ordinary MS has however a detection limit (~i0 -6 of the amount of 12C) which is not sufficient for our purposes. With accelerator mass spectrometry (AMS) it is possible to measure 14C down to i0 -14 of the amount of 12C. Comparisons show that AMS is more than a hundred times more sensitive than LSC. In 14C-triolein tests for fat absorption it was possible to demonstrate 14CO2 in expired air for several months after ingestion. 30% of the substance was catabolised rapidly, while the remaining 70% had a very slow turnover. The measurements have given possibility to calculate a realistic radiation dose, based on data for the total amount administered. The AMS-technique makes long-term studies of biokinetics of Z4C-labelled pharmaceuticals possible, and enables the use of much lower activity than hitherto in investigations on human. The dopamine reuptake system has during the last years been in the focus for studies of Parkinson's disease and other neuronal disorders with PET and SPECT. Commonly used PET radioligands are phenyltropane derivatives such as EC-11]I3-CIT and [C-I1][~-CFT which has been prepared by methylation of the norcompounds using [C-11 ]methyl iodide. Recently a new C-11-methylation reagent, [C-11]methyl triflate has been introduced (Jewett. 1992). We have performed a comparative study using these two C-11-1abelled precursors for the preparation of three radioligands, [C-11]I3-CIT, [C-11]I]-CFT and the novel radioligand [C-11]et-CIT. for examination of the dopamine reuptake system with PET. The reactivity of [C-11]methyl triflate is very high. [C-11]~-CIT, EC-11]I3-CFT and EC-11]a-CIT were all prepared in 60-90% decay corrected yield from [C-11] methyl triflate by reaction with 0.15 mg norcompound for 1 min at 60°C, while the yields using [C-11]methyl iodide and similar amounts of precursor with heating at 80°C for 3-5 min were 3-4 times lower. The products were all purified using straight-phase HPLC. The total radiochemical yields of the final sterile and pyrogen-free products were 40-60% (from [C-11]CO2, decay corrected) within 30-35 min from EOB. The low amount of precursors needed when preparing these dopamine reuptake ligands from [C-11] methyl triflate is important when considering the commercial availability and cost of the precursors mad also for the final HPLC-purification. The results demonstrate that using [C-11]methyl vitiate comparatively higher yields are obtained using shorter reaction times and at lower reaction temperatures, which improves the specific radioactivity of the products and are important for a reliable automated routine production for PET. K.A. Ber~str6m 1, C. Halldin, C-G Swahn, J.T. Kuikka 1, J. Tiihonenl,-L. Farde and E. L~nsimies 1. Kuopio University Hospital 1, Kuopio, Finland and Karolinska Institut, Stockholm, Sweden. tropane) has been developed as a radioligand for studying dopamine and serotonin reuptake in humans with both SPET and PET. [I-123][3-CIT was labelled with a specific radioactivity of >2900 Ci/mmol and radiochemical purity >98%. Informed consent was obtained from six subjects (three controls and three patients with Parkinson's disease) who were examined. The percentage of the radioactive metabolites and the parent compound was determined from venous plasma samples obtained up to 4 hours after injection of [I-123]!3-CIT. An HPLC method was developed that allowed a rapid analysis of many samples. Two metabolites of [I-123][3-CIT were found, a polar metabolite (P) and a lipophilic metabolite (L). The relative composition of plasma at time points 1,2 and 3 hours after injection of the tracer was (mean&+SD, n=6) 40_+7, 35+5 and 27_+7 (P); 11_+2, 29_+8 and 43_+8 (L); 49+_5, 36_+6 and 30+_8 (parent compound) respectively. Between 1 and 4 hours the percentage of the lipophilic metabolite increased whereas the percentage of the polar metabolite and the parent compound decreased. Compared to the results obtained from an earlier described ethyl acetate extraction method the HPLC method demonstrate a delayed appearance of the lipophilic metabolite. Due to the different labelling positions the analysis of [I-123][3-CIT metabolites provides additional information to that previously described for [C-11][3-CIT. In conclusion two metabolites were observed with an HPLC method after injection of [I-123] 13-CIT in humans. In recent years, other complexing agents such as tropolonate has been used for In-lll. Among the PET isotopes, Ga-68 has been used to label platelets. The short half-life ofGa-68 (68.1min) poses a severe limitation in situations where a longer waiting period is required for the tracer to accumulate in the organs of interest before imaging. We have already established procedures for a regular production of a number of medium half-life positron emitting radionuclides in our laboratory. Among these Co-55 (T½ = 18hrs), Cu-64 (T½ = 12hrs) and Ga-66 (T½ = 9.4hrs) have chemical properties similar to those of In and therefore their complexes with oxine would make good potential candidates for labelling ceils with these PET isotopes. With these objectives in mind, we have investigated the conjugation of Co, Cu and Ga to oxine at microscale and tracer level using atomic absorption flame spectrometry and radioactive tracers. Complexes of Ga with oxine precipitate quantitatively at a pH 2, complexes of Co-oxine at a pH of 4.5 and Cu-oxine at a pH of 2.7. In preliminary experiments, Ga-67-oxine labelled red blood cells with a 84% labelling efficiency. Experiments are underway for the labelling of lymphocytes, platelets and neutrophils with Co-55, Ga-66 and Cu-64. Since an increased number of clinical sites recently started with PET imaging they all are in need of getting a sufficient amount of 18-F desoxy glucose (FDG).The way to solve the problem is to find a method for FDG production at the clinical sites themselves. We report first results of PETrace MicroLab and quality of FDG. The MicroLab module produces automaticay 2-[18F] Fluoro -2-Desoxy glucose using 18-F Fluorid and Tetraacetyl-2-0-Tdfly-D-Manose. According to the regulations of Mulholland ~ phase transfer catalytic method was used.The catalyst is bound covalent on a polymer which serves for trapping 18-F Fluodd. 18-F-Fluodd is given automatically or by hand to a single use cartridge where the different steps for synthesis are running. Nearly the whole amount of 18-F/18-O endched H20 is saved on a reservoir and can be used again for FDG production. Quality control was done by ionexchangechromatography on a strong alkalinecolumne (CarboPacl, Dionex) with NaOH with gradienttechnic (start 15mM, end 55mM NaOH, runtime 50min, tret(FDG)=35min ). A amperometric technic was used for the detection of FDG. Within 6 month over 50 FDG production runs with MicroLab were performed.l.5 to 12 GBq 18-F-Fluorid were used starting the production whereas production time lasted 52 min. An overall average amount (not decay corrected) of over 32% FDG was reached. The TLC tested radiochemical purity was > 95% in 49/51 production runs. In one production no injectable FDG could be produced, because the F-18 contained volatile Fluodd compounds (presumably Freones). Meanwhile more than 130 patients could be examined with FDG produced by MicroLab without any side effects. Using the GEMS MicroLab the availibility of FDG will improve with good quality of the tracer. This is a main condition for the furher developement of PET studies at clinical sites. benzoindole rlngs bound by ni£rogen bridges, are a class of ~hotosensitizing agents which spontaneusly localize in, and are retained by, some solid tumors, causing destruction of these tumors upon illumination with red light, Feasibility of labeling Zn(II)-PC with 1-131 followed by incorporation into dipalmitoylphosphatidylcholine (DPPC) liposomes has been previously shown. We now report the biodistribution data of 1-131 labeled Zn(II)-PC-DPPC in mice bearing fibrosarcomas in the thigh (N=20). The uptake of this compound in tumor (T) , thyroid (TR) , liver (L) , kidne Z (K) and muscle The rapid uptake in tumor, which remained constant upto 90h, is similar to previously published data for the unlabeled compound in the same animal model. The elevated T/M ratios as well as the satisfactory tumor to normal (liver and kidney) and target (thyroid) organ ratios suggest the potential use of PC as carriers of long lived radionuclides for tumor therapy. The development of 99mTc complexes with receptor binding characteristics is one of the present challenges in synthetic radiopharmaeeutical chemistry. Currently we are pursuing experimental work with Tc-BAT-complexes exhibiting a neutral complex core and substituents with quaternary ammonium functions in the side chain. The 99mTc complexes which were obtained with high . . . . yields have been tested in animals for their affinity to organs comprising muscanme acetylcholine (m-ACh) receptors. Since the biodistributin data proved significant myocardial uptake with delayed washout the question arose whether the uptake values of the indicated compounds are either the result of their affinity to m-ACh receptors or to ACh esterase binding. Challenging experiments with atropin, a m-ACh antagonist, and phenyltrimethylammonium chloride, an ACh-esterase inhibitor, were performed and will be discussed. The organ distribution data, in % inj. dose/g organ weight, 5 and 60 minutes after i.v. injection into NMRI mice are summarized below: The fractionation of MAG3 cold kits provides an economical way for preparing Tc-99m MAG3. However, our nuclear pharmacy recently noted that fractionated Tc-99m MAG3 kits sometimes failed radiochemical purity (RCP) testing (Le., RCP < 90%) when older eluates were used. The purpose of this study was to evaluate the effects of eluate age on the radiochemical purity (RCP) of fractionated Tc-99m MAG3 kits. Each of 4 MAG3 cold kits was initially diluted with 10 ml N2-purged 0.9% NaCI solution and subdivided into 10 aliquots of 1-ml MAG3 solution and overlayered with N 2. The 40 fractionated MAG3 vials were immediately frozen at -20°C for storage. Fractionated MAG3 kits were reconstituted with 1 ml of 1,110 MBq Tc-99m eluate from a long-ingrowth generator (Le., > 72 hr) at every hour during the 6hr post-elution period. The RCP of each Tc-99m MAG3 preparation was determined using the recommended Sep-Pak ® C18 column chromatography at 1, 2, 3, 4, 5, and 6 hr postreconstitution. All fractionated MAG3 kits prepared with generator eluates 4 hr old or less maintained an average RCP value of 96.3 + 2.5% (n = 144) throughout the 6-hr evaluation period following preparation. However, Tc-99m eluate that was 5 hr and 6 hr old after elution resulted in kit failure rates of 16.7% (1/6) with RCP = 89.3% and 50% (3/6) with RCP = 88.2%, 83.9%, and 87.1%, respectively. These data suggest that the use of Tc-99m eluate of more than 5 hr old for the preparation of a fractionated Tc-99m MAG3 kit is associated with a high rate of kit failure and should therefore be avoided. Evaluation of radiopharmaceutical quality is an important task for scientists in the Nuclear Medicine field, from both an economical and technical point of view. The Italian Association of Nuclear Medicine (AIMN) thus encouraged and supported a multicenter program on quality control of Tc 99m generators supplied in our Country. Six participating Centers checked more than 100 generators over six months, measuring elution yield and profile, pH, aluminum and other metal breakthrough, radiochemical and radionuclidic purity, by rapid semiquantitative methods and accurate reference techniques. Some of the results are reported: ~ COMPANYi IITOT pH median 6 5.35 6 6 6 6 6 range 5.5-6.5 4.3-6.1 5.0-6.0 4.5-7.0 5.0-6.0 5.5-7.0 4. The development of the program provided AIMN with an up to date description of the National market for one of the most important radiopharmaceuticals and helped establish a number of reference Centers for information and support on this subject for other Clinical Institutions and local Authorities. A. Steinstrgi3er L. Kuhlmann, B. Haase, L. Warzecha Radiochemical Laboratory, Hoechst AG; Frankfurt/Main, Germany Radiolabeliing of monoclonal antibodies (MAb) can decrease their immunoreactivity. We studied the influence of different labelling procedures. For this a method was established to measure immunoreactivity of labelled and unlabelled MAb. After incubating the MAb with antigen positive tumorcells this procedure is able to quantify simultaneously bound activity and unbound antibodies for a direct comparison. The labelling procedures for MAb can be divided into different categories: direct/indirect (i.e. without or with an additional linkage group) or sitespecific/allover (i.e. avoiding an impairment of the binding region of the MAb or not). Labelling by using a chelating agent (e.g. for In-111) is an example for an indirect, non sitespecific procedure. Immunoreactivity is influenced by the amount of chelate and also by the amount of nuclide bound. In routine the decrease amounts to 15 -30 % for these compounds. Most of the iodination procedures are direct but also non sitespecific. No difference is to be seen between 1-131 and 1-125. The decrease of immunoreactivity is 5 -15 %. Increasing the specific activity normally has no influence on immunoreactivity but on stability of these compounds. For the labelling of monoclonal antibodies with Technetium-99m different techniques are known, but in this context only the "Schwarz-method" is discussed. It is a direct method and is with high probability sitespecific. For this labelling procedure no influence on immunoreactivity of the monoclonal antibody was to be seen. Even increasing the activity excessively reduces not the immunoreactivity, but can decrease the radiochemical purity. To define the role and quantitate endogenous sulfhydryl (eSH) groups generated by 2-mercaptoethanol (ME) reduction of antibody series of experiments were performed. Human IgG and model anti CEA MoAb (IOR-1) were reduced with ME at molar ratio of 1000:1; 3000:1. After 30 minutes the solution were purified on Sephadex-G-50 columns. The OD of collected fractions was determined and appropriate fractions pooled. Aliquotes were frozen and stored at -70°C or lyophilized. The quantitation of SH concentration was accomplished by EIIman's reagent, absorbance was measured at 412 nm. Integrity of MoAb's samples after reduction were determined by non-reduced PAGE and size exclusion HPLC. Radiolabelling with Tc-99m of thawed and freeze-dried antibody using stannous (II)-PYP was done followed by radio HPLC and biodistribution study in Balb/c/Lati/nude mice bearing CEA positive human colorectal adenocarcinoma xenografts. The number of eSH group generated at a two ME:MoAb molar ratio were calculated to be 2.2/hlgG molecule and 3.4/anti CEA molecule. During lyophilization the number of free SH groups decreased by 15 % (hlgG) and 30 % (anti CEA). Stannous ion added prior freeze-drying prevented the re-arrangement of a eSH. At 50/ug of SnCI 2 x 2H20 more than 95 % labelling was obtained. FIPLC analy~s of reduced and radiolabelled MoAbs showed one major peak (9o %) with a retention time identical to the unreduced species. Biodistribution showed high activity in blood pool, kidneys and tumour (8.3 % ID/g tumour at 6 hrs). eSH groups generated at controlled conditions provide a stabil binding side for 99mTc with retained biochemical quality and immunological function of MoAbs. Because of its anti-tumour properties, we have examined the binding of tumour necrosis factor-alpha (TNFec) to turnout cells in vivo and in vitro. In our laboratory a new magnetic separation radioimmunoassay has been developed for measurement of TNF~. Thereafter the radiolabelled TNF~ was used in radiobioassay. The parameters of the RIA a r e as follows: specific activity of tracer 7-8000 kBq//ug, sensitivity: 10 pg/ml, NSB: 1-2 %, B/B o 40-50 % (at dilution of antibody: 6000), recovery: 90-95 %, measuring range of assay: 0-104 pg/ml, time of assay: 24 hours. It was found that the sera of mice bearing colorectal adeno-carcinoma contained higher amounts of TN~, (500-800 pg/ml) as compared to the values for normal animals: (20-100 pg/ml). For radiobioassay, labelled TNF=¢, specific activity: 2-3000 kBq//ug TNF,¢ ,was injected intravenously into tumourbearing m=ce, and the distribution of tracer was followed 1, 2 and 3 hours after i.v. injection. The highest level of radioactivity (9-12% of injected activity) in tumour tissue was detected by 2 hours of i.v. injection. In vitro studies of 125-I-TNF~ binding to tumour cells were performed on Calu-1 cell culture (a line established from human lung carcinoma). 125-I-TNF=¢ (37 kBq/2000 U/ml) was added to the proliferating cells at various time-points of culturing. By measurement of bound radioactivity, information was obtained on the ability of cultured tumour cells to bind TN~ in the control experiments and also after the effect of ionizing radiation (0.25-4 Gy). Radiation-induced cell membrane perturbation was followed by dose-dependent changes in TN~: binding, too. The applied RIA method seems to be suitable for determination of the concentration of TNF~. in sera. 125-I-TNF,¢showed high localization in tumour tissue and slow blood disappearance. The purpose of the study: In past few years in 16 patients (pts.) under the radiation therapy the acute radiation pneumonitis (ARP) was discovered. In 9 patients with the small cell lung cancer (SCLC), in 5 with breast cancer and in two wdth Hodgkin's disease the prescribed doses were 46 and 60 Gy (in 11 pts. the therapy was finished). Nearly few years we tried to test the secretion of APUD endocrine cells in patients under the radiation therapy, to see if the levels of neurotransmitters may indicate the radiation damages. Methods: Somatostatin and VIP were determined in patients sera by RIA kits from Prof.Bloom Laboratory (London) and NSE (a good indicator of lung tissue and spine damages) by RIA CIS.Gastrin was determined by RIA CIS. Patients with lung cancer, breast cancer and with Hodgkin before Rth in ARP Somatostatin(pmol/1) 10,6~4,1 112,1343,2 ~ VIP (pmol/1) 6,1~2,7 34,1~9,6 ~ NSE (ug/l) 13,9~5,3 9,2~3,5 Gastrin (pmol/l) 24,7~13,1 11,533,5 ~ P i 0,01 Conclusion: The significantly high somatostatin and VIP serum levels in ARP were caused by low gastrin levels (gastrin cells radiation damage). The spine was not seriously affected by radiation therapy (low NSE serum levels) and also that the treatment was successful in patients with SCLC. PSA-levels in blood are of great importance and interest for the diagnosis and follow up of prostate cancer in various stages. We checked the technical aspects and clinical usefulness of a PSA estimation in urine. a) Estimation of PSA levels in urine of normal men and women, looking for circadian rythms, 24h values and various influences (stability, reproducibility, pH values, ejaculation, location of excretion), using a commercial IRMA (Tandem-R, Hybritech). b) Specimens of 64 patients with cancer of the prostate in stage A-C were analyzed for PSA levels in blood and urine before and after radical prostatectomy. The technical performance was as good in urine as in blood. No PSA was found in the urine collected by nephrostoma.There was a maximum of PSA at noon and at midnight. Midstream values were as representative as a 24h collection. Values of normal men and patients with prostate carcinomas showed large variations. 25 patients without chemotherapy after radical prostatectomy demonstrated urine values between 0 and 8,3 ng/ml whereas 87% of 30 patients with endocrine therapy after radical prostatectomy had values below 0.3 ng/ml of PSA in urine. PSA in urine is not excreted by the kidneys, independent from residual tumor tissue but excreted by periurethral glands, which are strongly influenced by endocrine therapy. The potential clinical use of a PSA determination in urine might be the termination of adiuvant chemotherapy and the control of patient compliance during endocrine therapy. Both assays showed an excellent overall correlation (r=l.0) for the range from 0.1-3500 ng PSA/ml. This was also found for the range from 0.1-4.0 ng/ml (n=224), the slope beeing almost 1.0 with a minimal offset : ACS = 0.94 x Hybritech + 0.11 (r=o.94). Looking for the range from 4.0 -20.0 ng/ml (n=81) the r-value decreased to r = 0.88 and the slope went up: ACS = 1.43 x Hybritech + 0175. Selecting the values between 20 and 3500 ng/ml (n=123) the slope was lower and the offset greater: ACS = 1.27 x Hybritech + 7.2. After radical prostatectomy patients showed comparably low PSA values (<0.4 ng/ml) in both assays, the ACS values beeing more differentiated. In case of tumor progression ACS values rose more prounced in all cases. Demonstrating a high correlation in the normal range, the ACS values seem to provide a more pronounced differentiation of tumor progression due to a steeper rise. On the other hand after a long period of high inter-assay compatibility for PSA values the new technique of ACS to estimate also uncomplexed PSA makes it necessary to label the results of each PSA estimation with the name of the applied kit. The. development of fully automated analyzers that performs immunological tests using the ELISA principle, is an atmcfive option to change the methodology of those tests from IRMA to ELISA. In the follow-up of the patients it is imperative that the values deternfined for the tnmour markers levels by the different methods should b e comparable, In order to solve this problem we have analysed the values of CEA and CA 19-9 determined in l 11 and 129 sel"um sanlples respectively by both methods and distributed along all the extension of the curves and including also diluted samples of those serums which values were superior to the last point of the curves, CEA:We considered two levels of CEA vahies, superior and inferior to 7 ng/nfl in IRMA.The differences of the IRMA and ELISA values were "nlarginally" different fl'om zero (paired t lest, s.l. =0.05) for the low level (<7 ng/ml), and not significantly different from zero for the high level values (> 7 ng/ml), and for the lo|ality of the values, CA 19-9: For this parameter we considered tin'ee levels 0-37, 37-240 and >240 ng/nfl.The differences of |he values obtained by IRMA and ELISA were re17 significantly different fl'om zero for the low level vahles of the pm'anleter, "not significantly" for the medium level and " marginally" different for the high values ( paired t tes, s.l,=0.05 ).For lhe totality of the values the difference is also "mm'ginally" different fl'om zero. The results showing differences between the paired values that were superior to the acceptable errors of either method indicates the necessity of study correlations between both values and to establish correlation expressions, chic correlations were all statistically significant ( | test of correlation coefficient, r ). The linear and logariflmlic correlation expressions obtained for the different levels of hmmur markers are presented and discussed. rCBF CHANGES IN PATIENTS WITH NEGATIVE SCHIZOPHRENIA AND UNIPOLAR DEPRESSION USING 99n1-TC-H~PAO Hansen Garden State Cancer Center at the Center at the Center for Molecular Medicine and Immunology Nieweg Several papers report on the value of T1-201 and Tc-99m-MIBI in non 1-131 concentrating, or in dedifferentiated thyroid tumors. The aim of the present study is to evaluate and compare the actual role of both the tracers in selected pts. with DTC, showing high thyroglobulin (Tg) levels together with negative 1-131. Among 45 pts. examined by Tg determination and I-131/TI-20 lfrc-99m-MIBI scans during the follow up MBq) scans were obtained in all pts; Tc-99m-MIBI (555 MBq) scans were obtained in 7 pts When compared with T1-201' results, of the 5 MIBIpositive studies 3 were fully concordant with T1-201, two had some lesions missed. Clinical follow up showed the presence of metastases in all patients. Conclusions: 1) the need of alternative radiotracers in non 1-131 concentrating tumors is confirmed. 2) TI-201 seems to have a higher sensitivity in patients with elevated Tg levels and negative I-131 scan than in the overall series of DTC Tc-99m-MIBI which is more easily available and more suitable for SPET than T1-201, does not seem to actually improve diagnostic efficacy IMMUNOSCINTIGRAPHY WITH F(ab')2 OF 225 Department of Clinical Pathophysiology ET) is a potent vasoconstrictor 21 aminoacid peptide originally isolated from culture supematants of pomine endothelial cells. In search of the genomic DNA library, three distinct human ET-related genes were cloned and designated ET-1 We report immunoreactive ET in urine. 5 ml urine were treated with 800 ul of diluted acetonitrile 1:1 (v/v) with water. ET was extracted by Sep-Pak C18 cartridges (Waters-Millipore) using methanol/water as the mobil phase. The peptide was eluted with methanol/water in the volume ratio of 85/15, evaporated to dryness and reconstituted in 250 ul RIA buffer. We used the ET-RIA system available from Nuclear Medicine, Lung Diseases, Thoracic Surgery, Med.Academy of Gdansk, Gdansk Poland CLINICAL EVALUATION OF CYFRA 21-1 IMMUNORADIOMETRIC ASSAY AS A MARKER FOR LUNG CANCER Cyrokeratin 19 is a subunit of cytokeratin intermediate filament expressed particulary in epithelial tumor cells including bronchial cancers. The purpose of our study was to asses clinical value of Cyrfa 21-1 immunoradiometric assay from CIS Biointernatienal for lung cance~ Serum levels cf Cyfra 21-1 were 20 patients with benign lung disease and in 60 healthy individuals /30 non-smokers and 30 heavy smokers/. The mean cytokeratin 19 level in controls was 0.69 ± 0.37 ng/ml/S.D./. In a group of patients with nom-malignant lung diseases the average value was 0.84± 0.32 ng/ml. Cyfra 21-1 serum level in patients with lung cancers was significantly higher -all cancers 7.84 ± 13 Using a threshold of 1.53 ng/ml, sensitivity and specificity were 0.68 and 0.95, respectively. Levels of Cyfra 21-1 was strongly associated to presence of metastases and performance status in NSCLC patients /p <0,001 by ANOVA for both/. Conclusions: I/ Cyfra 21-1 assay is clinically useful in NSCLC patients, 2/ In this type of lung cancer Med. Nuclear, Hospital Clinic i Provincial and CETIR, Centre M~dic The radiochemical purity of Tc-g9m ECD, labelling efficiency of leucocytes, cell v i a b i l i t y of labelled leucocytes, and s t a b i l i t y of Tc-99m ECO labelled leucocytes were calculated 8% (n= 21) and 24,5 ± 3.7% (n=14) respectively; from Tc-99m HMPAO labelled leucocytes at 1, 2, 4, 6, 8 and 24 hours were 11.5 ± 1.5%, 16.7 ± 1.3%, 20.6 ± 2.1%, 25,6 ± 2.5%, 29.7 ± 2,1% and 38.7 ± 3.1%, respectively in plasma after labelling (n= 21). The disintegrated percentage from Tc-99m ECD Previous studies have shown hypoperfusion of different brain regions in depressive and schizophrenic (SCH) patients using functional brain imaging technique such as the 99m-Tc-HMPAO-SPECT.The aim of our study was to compare results obtained by this technique in two psychiatric disorders characterized by overlapping clinical symptomatology (negative SCH versus unipolar depression).For this purpose we studied 25 patients, 15 with negative SCH and 10 with unipolar depression. All patients fulfilled DSM-III criteria and were on prescribed medication. SPECT images were acquired after iv. injection of 20 mCi 99m-Tc-HMPAO using a dual head rotating gamma camera. Following reconstruction and attenuation correction, coronal, sagittal and reoriented transversal slices (parallel to the orbitomeatal line) were obtained. Thirty-two ROI's were drawn in the frontal, temporal, parietal and occipital lobes, the basal ganglia and the cerebellum for semiquantitative analysis, normalized to the mean cerebral uptake. Only regional asymmetries >15% were considered abnormal.17 patients showed regional hypoperfusion abnormalities in frontal, parietal and temporal lobes (10 with negative SCH and 7 with unipolar depression), and 8 patients had no changes in rCBF (5 with negative SCH and 3 with unipolar depression). There were 23 regional hypoperfusion abnormalities in patients with negative SCH and 22 regional hypoperfusion abnormalities in patients with unipolar depression, almost all (except 3 hypopeffusions in 2 depressed patients) localized in left dominant hemisphere. Statistical analysis (2-tail Student's test, p>0.05) showed no significant differences between SCH and depressed patients..In conclusion, we found that 99m'Tc-HMPAO-SPECT could be usefull and sensible tool to diagnose rCBF abnormalities, but not for differentiation between patients with negative schizophrenia and unipolar depression. However, further studies are needed to evaluate the clinical significance of this findings. Twelve in-patients, fullfiling DSM III-R criteria for Schizophrenia (disorganized form) were assessed twice with SPECT, initially when drug free and secondly after 28 days treatment. All of them were assessed during a semi-structured interview with the SANS at DO and each week ; the patients suffered from a negative form of illness defined by an initial SANS score > 65. All of them were treated with low doses of amisulpride per os (400mg/d the first week ; between 50 and 150mg/d the two last weeks). The imaging procedure by SPECT with 99m-Tc HmPAO (Tomomatic 554 Medimatic) was performed after the clinical assessement, at DO and D28. The data analysis showed significant differences in the regional Cerebral Blood Flow indexes before and after treatment (Wilcoxon test). The frontal regions of interest showed the most striking variations, particulary in the right side and in the dorso-lateral prefrontal aerea (p= 0.018). We also found significant variation of the asymmetry in the medio-frontal aerea, before and after treatment (p= 0.05). We showed significant correlations between some rCBF variations and some symptomatic SANS We cannot talk about an eventual "amilsulpride effect", whithout a control goup with placebo : we supposed on an "improvement effect". Although several patterns of cerebral perfusion abnormalities were described, it is not uncommon to have difficulties in interpretation of brain SPECT images of psychiatric patients. In this study, we looked for a correlation between some common symptoms and cerebral perfusion abnormalities in atypical psychiatric patients. 20 patients (mean age: 43; 13 M, 7 F) were included in the study. Brain SPECTs were performed after intravenous injection of 15-20 mCi of Tc-99m HMPAO, using a single detector, rotating gamma camera, with eyes and ears closed, in a quiet room. Tomographic slices were evaluated visually. 32 decreased perfusion areas in 20 brains were detected. Distribution of the lesions was as follows: 50% left frontal (LF) codex, 30% in left temporal (LT) codex. 13% right temporal (RF) cortex, 7% right frontal (RF) codex. Lesions were grouped as inthe Patients with psycotic symptoms 1 (12.5%) 2 (40%) 2 (67%) 4 (100%)Major symptoms were 1) depressive mood (DM), 2) social isolation (SI), 3) decreased performance (DP), 4) psychomotor retardation (PR), 5) hallucinations (H), 6) delusions (D). In patients who have LF cortex hypoperfusion the most common symptoms were DP (13.4%), DM (11%) and SI (11%). We observed a tendency for H and D to be related to temporal codex lesions.In conclusion, it seems that solitary LF hypoperfusions tended to be with DM, SI, DP and with less probability of psycotic symptoms, while additional and temporal lesions alone were likely to be related to psycotic symptoms. Three patients with temporal lesions had a final clinical diagnosis of schizophrenia which might suggest that brain perfusion scanning can predict the possible outcome in dealing with atypical patients. Biersaek. In patients with obsessive compulsive disorder, the mostly recent PET studies suggest an involvement of the frontal lobes and the basal ganglia. To evaluate rCBF by means of SPECT and to relate the findings to clinical variables (psychopathology, duration of disease, medication) we investigated 15 patients using high resolution SPECT (ASPECT, FWHM 5-6 mm) and ~mTe-HMPAO as a tracer. In addition to visual evaluation, ROIs were drawn on the mesial and lateral, the frontal, parietal and occipital lobes, the basal ganglia, and the cerebellum. The mean age was 37 + 11.3 years, the mean duration of disease ranged about 14.6 + ]-0.7 years. The Yale Brown Obsessive Compulsive Scale (Y--BOCS) was used to quantify psychopathological symptoms. Only one patient demonstrated a normal SPECT. In 13 subjects a reduced regional perfusion was observed, while 6 patients showed an increased regional perfusion. The diminished perfusion clearly lateralized to the right side (16 right, 8 left). The predominantly affected region was the temporal lobe (6 right, 3 left). In contrast, the hyperperfusion did not show major side differences (3 right prefrontal region, 4 left prefrontal region) . It was mainly confined to the prefrontal area. Thus, our preliminary findings further suggest an involvement of frontal lobe structures in patients with obsessive compulsive disorder. Moreover, our results demonstrate hypoperfusion of the temporal lobe as it has been observed in other psychiatric diseases. Due to the number of patients evaluated up to now, valuable statistics correlating the SPECT findings to clinical variables could not be established yet. F-18] FES) for the in-vivo imaging of e s t r o g e n r e c e p t o r s (ER) in human meningiomas, tumours known to be influenced by sex hormones during p r e g n a n c y and the luteal phase, the cerebral u p t a k e of [F-18] FES was e x a m i n e d in 6 p a t i e n t s The aim of this study was to evaluate the role of the immunoscintigraphy in diagnosis of the colorectal carcino ma. This method was not develop till now in Poland and this multicenter study is the first project concerning usefulnes of RI5 in our country. Monoclonal antibody B 72.3 (CYT-103)labeled with ill-indium chloride were used. 42 patients with high suspiotion of cancer were studied.Two group of case were selected:e.with primary tumour and b. with local recurren ce. A single dose of 1.0mg labeled antibody (4.5-5.5 mCi) was administered.Vital signs were monitored during and 60 min. after injection.Gamma cameras ZLC Siemens were used.Examinations were performed in all cases twice or third between 24-72 hs. after injection of the tracer.No adverse reactions after injection of CYT-103 were noted. In the group a 21 out 25 examinations showed true positive results.The sensitivity was 84%. In the group b true negative results were observed in 6 cases,true positive -in 8 cases and false negative -in 2 cases, The sensitivity was 80%. In conclusion: CYT-103 scintigraphy has proven to be a safe and promising method in diagnosis of colorectal primary as well as recurrence neoplastic process. The purpose of this study was to evaluate the feasibility of 99m-Tc in lesion detection,differentiation of benign or malignant nature ~nd post~herapeuthic follcw-up of primacy bone tumors. A total of 27 patients were studied.Mslignant bone tl~ors were ccmposed of osteosarcomas (5) ,Ewir~'s sarcomas (6) and Chondros~ (4) .6 individuals (4 ostsasarcc~ra and 2 Ewing's serccma) were imaged postaperativly in order to ir~esti~ts reecturrencas.6 patients with patholo-~vically proven benign bone lesions were also studied.The patients were IV injected 555 MBq 99m-To C~.3,6 and 24 hrs.aftsr injection plsrer scintigr~6~s were obtained.Increased sotivity ecct~ulation in comparison wi~d~ centralateral extremity was socepted as positive.Quantitative evaluaticrs were also applied by FOIs dramn over lesicns and contralateral site (~C).All patients were also ex~uined by 3 phase b~ne scintigrsphy,x-rsy,CT and MRI.Patholq~cal exanination determined final disgnosis.13 of 15 primary bone tumors demastrated positive G~ aasu~ulation. Pesttherapeuthic ~ of 2 of 4 astecssrcares snd 1 of 2 patients with EWir~'s sarscmas shewed increased uptske pathologically consistent widu local recurrence.All benign bone lesions demastratsd abcent 99m-Tc G_w4 soasmulaticn e~cept i astsoblastcma.Tne mean L/CLuptake rati~ of T T primary b3ne tu~rs end benign bone lesions were 2,4-0,3 and 1,01-0,3 respectively (p(O,05).The sensitivity and due specificity of 99m-Tc G~M in differsntiatior~ of malignsnt tumors from becign bcne lesicrs were 87 % and 92 % respectively.In conclt~ien, in this preliminary study 99m-Tc GS~ was found as a proraising sgant in the evaluation of primary bone tumors,especially in discrimip~tion fran ben~ lesions and in prediction of postoperative recourl~e$. Re-188, which can be produced from a generator system using W-188, has been considered suitable for the radioimmunotherapy.The purpose of this study was to determine the efficiency of Re-188 labeled monoclonal antibody (MAb) for tumortargeting. MAb B72.3, a murine IgGl reactive with human carcinoma antigen TAG-72, was labeled with Re-188 by a direct conjugation using tin as a reduction agent. The MAb was also labeled with 1-125 by Chloramine-T method. In melanoma patients without apparent lymph node metastases, the S.N. procedure allows us to identify those who have micrometastases and need regional lymph node dissection (R.N.L.D.). We investigated the gamma detection probe and patent blue (P.B.) for this purpose. In 9 patients with clinically localized melanoma with a mean Breslow thickness of 2.3 mm (range 1.1 mm-4.7 ram) the SN identification and biopsy procedure was carried out. Approximately 60 MBq of 99m Tcnanocolloid was injected intradermally in the margins of the turnout or at the previous tumor site and shortly thereafter the first lymphoscintigram was made. The first visualized lymph node (S.N.) was then marked on the skin. The next day P.B. was injected shortly before operation at the same location as the 99mTc-nanocolloid. The number of identified S.N. with the gamma camera was 15. During operation we identified 11 out of 14 S.N. visually by its blue discoloration and 14 out of 14 with a gamma detection probe (Neoprobe 1000). The mean S.N. to background (BKG) ratio intra-operatively was 73.2 (range 3.5-359) and the mean S.N./BKG ratio ex vivo was 1125 (range 70-3957). The mean percentage of injected dose per gram tissue was 1.36 (range 0.02-5.37). Frozen section microscopy performed during surgery revealed in 2 patients micrometastases. Both patients underwent RLND. Conclusion: Accuracy and reliability of this method appear to be very high. When carried out in a larger number of patients this procedure might be useful in the selection of patients for RLND or whether a waitand-see policy can be followed. The estrogen receptor specific radioligand Z-[I-123]MIVE, which in earlier studies showed high binding affinity in vitro and high target tissue uptake and selectivity in the rat in vivo, could be a suitable radioligand for estrogen receptor-positive human breast tumours. To date, its distribution was studied in three healthy female volunteers. After i.v. injection of 185 MBq Z-[I-123]MIVE (specific activiW 200 MBq/nmol) a dynamic acquisition of the thorax was performed between 0 and 30 min. Anterior and posterior whole body scans were made at 1, 2, 4 and 6 hr. ROI s ware drawn to calculate the biodistribution. The organ activity was expressed as percentage of the total body activity. Blood samples were taken at different times after injection, and urine was collected. Lung and heart activity decreased exponentially within 10 rain to 30% of the maximum, remaining almost constant thereafter. Liver activity increased to a steady state at 10 rain. The 30 min blood level was about 94% of the 5 rain activity, and decreased to 32, 19, 10 and 3% at 1, 2, 4 and 24 hr, resp. In agreement with the decrease in total body activity, the total urine excretion at 6 hr was 20% of the injected dose. Urine excretion increased to 30% at 20 hr. Organ distribution was as follows :The mean activity (counts/pixel) in the breast, expressed as percentage of the mean lung activity, increased from 97% at I hr to 120% at 6 hr, We conclude that Z-[I-123]MIVE is a promising radioligand for SPECT imaging of estrogen receptors in human breast cancer. The Authors have applied SMS scintigraphy in the imaging of MTC which shows high affinity SMS receptors. We report the results of this technique in 6 totally thyroidectomized pts. (4 F and 2 M, aged 38-69 yr) who presented recurrent and/or metastatic lesions and high levels of calcitunin (Ct) and CEA. In all pts. the Ct response to acute administration ofoctreotide (OCT) (200 ~tg s.c.) was evaluated. Whole body SMS scans (4 to 48 hrs) were performed after i.v. injection of 111-158 MBq of In-lll-pentetreofide. When indicated, SPET was carded out. The SMS results were compared to those of Tc-99m-(V DMSA and 1-123-MIBG scans. The', are listed in the Preliminary biodistribution studies on male mice bearing mamma-carcinoma will be reported.Our first results suggest that *I-DSEP is a useful tracer for estrogenreceptor mapping and might also be suited for radionuclide therapy. Weisner et al. recently (EJNM, 20, 8, 1993) succeeded in stabilising Tc-HM-PAO in vitro by the addition of cobalt chloride. Coles and Dickett were able to demonstrate in the rat its irmocuousness in doses up to 1000 times the quantities applied in normal medical use (personal communication). The aim of this study was to test this observation in humans, both as to stability and harmlessness.Thirty-four patients gave their consent to participate in the study. Ceretec ° was obtained from 3.7 GBq fresh Tc-pertectmetate from the 2nd generator elution (2 types of generators were used). Cobalt chloride (200 ug/2 ml) were added 2 rain alter reconstruction. Thirty patients were injected with 0.9 to 1.3 GBq of Tc-HM-PAO reconstituted for less than 2 hours. The cerebral tomography was started 20 rain. after. Moreover, in 4 extra patients, leucocytes were labelled with more than one hour old tracer, the yield of the labelling being measured. Clinical parameters were followed up to 24 hours after injection. The images obtained were compared both visually and quantitatively (in the brain studies: distribution within the brain and the brain/soft, tissue proportion) to those obtained in a control group, matched for age and sex, and using non-stabilised Tc-HM-PAO, injected within 30 min.No toxicity or other side effects were noticed. There was no significant difference between the images of both groups. The yield of leucocyte labelling was statistically unaltered.The use of cobalt chloride as a stabilising agent for Tc-HM-PAO, proved, within the scope of this study, to be elficacious in routine application and harmless for the patient. rnsulin-like growth factors (IGFs) are peptides that express anabolic and mitogenic activity on fetal, postnatal and transformed cells. In serum, IGF's circulate bound to IGF-binding proteins ( IGFBPs... mostly IGFBP-3 ) which modulate their proliferative action. Several adenocarcinoma secrete IGFBP's and express binding sites for them.Purified glycosylated human recombinant IGFBP-3 (42kDa) was labelled with 1-125 and injected into non-anaesthetized rats.Concentration-time profiles were studied in blood and various organs.Autoradiography was done on major organs of localization.Urine and blood samples were analyzed by gel permeation chromatography.Over 80% of the blood pool activity cleared by 30 min. Gel permeation chromatography revealed radioactivity retained in the blood pool was bound in the 150 kDa ternary complex normally found in plasma. Blood pool activity decreased to 4% by 6 hours and 0.7% at 24 hours. Liver and kidney activity peaked at l0 minutes with 24% and 5.8% respectively.In humans, the liver acts as the major site of IGF production.The majority of the 12.8% in the stomach at 2 hours was present in the contents.Less than 1% id was in the GIT and contents by 24 hours.Autoradiography of liver samples indicated localization in Kupffer cells.In humans the mRNA for IGFBP-3 has been shown to exist in Kupffer cells. Autoradiography revealed the major kidney localization was in the glomerulus and distal tubules. Gel permeation chromatography of i0 minute urine samples indicated the protein renally excreted had been metabolized to lower molecular weight forms (<18kDa). In the stomach most of the radioactivity was localized in the epithelial mucosa. Some localization was also evident in the smooth muscle of stomach and small intestine.Somatostatin was previously found to have an improved biodistribution (|renal, |hepatobiliary clearance) when labelled via bifunctional chelates rather than radioiodine. Further studies are planned on tumour bearing animals and with IGFBP's radiolabelled with bifunctional chelates. The cerbB2 oncogene was proposed as a prognostic indicator in human breast cancer. In this study we evaluated 4 methods to measure the cerbB2 protein expression in order: a) to compare two IRMA kits (ELISA, Oncogene Science (ONC) and EIA, Triton Diagnostic (TRIT)), with the immunohistochemical assay (IHC) and Western blotting (WB); b) to compare the relationships between cerbB2 protein levels obtained with the different methods used and some other parameters. Tissue samples from 250 patients with primary breast cancer were partly formalin fixed and paraffin embedded for IHC (mAb clone 3B5 -ONC) and partly pulverized and homogenized in phosphate buffer. The homogenates were in part lysated and assayed for WB and ONC assays and in part ultracentrifuged. The pellets were lysated and used for TR1T assay. Positivity rates with IHC was 28.5%. We categorized samples analyzed with WB, ONC and TRIT as overexpressing (OEx) and no-OEx (-) using a cut-off obtained from non-malignant specimens. Using the second cut-off the positivity was 28%,26% and 28% respectively. The differences between the 4 methods were not significative (Cochran Q test: p= 0.677) The concordance rates range between 76% (WB vs TRIT) and 90% (ONC vs IHC). 78% of the low-OEx samples identified by WB and TRIT and 93% identified by ONC were negative with IHC. The relationships between erbB2 and both ER and PR showed an inverse association, independent of the method used. However, ONC and TRIT showed direct correlation between CerbB2 and both ER and PR in erbB2(-) samples, and an indirect one in cerbB2(+)/(++) samples. All the methods showed a trend toward higher positivity rates of erbB2 in samples with more than 3 positive lymphnodes. Moreover, in the cerbB2 (+)/(++) group assayed by ONC and WB higher cerbB2 levels in N+ then N-samples were found, while an inverse trend was found in erbB2(-) samples. In conclusion, the four methods results seem to disclose confident correlation indexes. The purpose of the study was to investigate whether SPECT studies using 5-[~=~I]iodo-2'-deoxyuridine (~IUdR) produce the same results. A reliable procedure, using an lode-bead ® as oxidizing agent, was developed for labelling of 2"-deoxyuridine with ~=~I. Optimization of the reaction conditions (pH i; 15 mln; 90°C) resulted in a labelling yield of at least 65 %. The production time was less than 1 h. Three adenocarcinoma-bearing rats were injected with ~ZC-TdR and z~ZIUdR (370 and 3.7 MBq). The rats were recta linearly scanned with a PET-camera, a y-and a SPECT camera. The PET and SPECT Scans were visually comparable. All animals were sacrificed and the organs measured for ~zzI activity.Preliminary results suggested the behaviour of both radiopharmaceuticals being similar. Additional tests will be necessary to investigate the ~orrelation between cell proliferation in tumours and the amount of ~aIUdRuptake. ~I U d R i n combination with SPECT offers the possibility of nucleoside uptake studies (DNA-synthesis) in centres without PET facilities. A TLC method was developed to model the interaction of radiopharmaceuticals with brain tissue. In this method, mouse brain microsomes, from cerebral cortex, were coated onto a zone of a TLC strip, the unreacted sites blocked with gelatin, and the test radiopharmaceuticals (100 -500 K cpm) chromatographed over the brain materials. Brain reactive materials bound to the microsomes and were separated from the unreacted materials by the mobile phase (PBS containing 60% serum and 4% ethanol). Strips coated with gelatin (no microsomes) were used to assess non-specific binding.Using this format, Tc-99m-HMPO was found to interact with the microsomes (63%) whereas the kidney imaging agent Tc-99m-MAG3 did not (3%). Tc-99m-ethy1 cysteinate interacted poorly (9.9%), a result consistent with its known inability to be metabolized by nonprimate brain tissue. In-I 11-DTPA-octreotide was also bound (up to 25 %). Other experimental peptide radiopharmaceuticals (Tc-99moctreotide and a Tc-99m-Iaminin-derived peptide) were also found to bind to the microsomes. Binding tO the negative control strip was consistantly low and frequently below 5%.In this assay, there are neither wash steps nor centrifugation steps, and assays can be completed within 15 minutes. The assay may be useful in monitoring of the interaction of established and experimental brain imaging agents with brain tissue. Multiple neuroreceptor changes are present in Alzheimer disease (AD); in particular, a consistent loss of nicotinic receptors in cortical tissue was reported. For future clinical studies with SPET we aimed at labeling a ligand with 123I and with sufficient specific activity. 1-3 mg 5-bromonlcotine were autoclaved for 60 ~ with 123I-NaI in the presence of 1 mg copper chloride and glacial acetic acid (pH 4.7). The labeling efficiency was 69 %, the radiochemical purity exceeded 95 % (I-~LC and thin layer chromatography). A specific activity of 180 GBq/mmote was obtained by H~LC separation of the excess of 5bromo-nicotine in the reaction mixture (RP 18 Eurospher 80 C18; methanol:10 mM phosphate buffer = 45:55). This product (H) and another one with lower specific activity of 0.2 GBq/mmole (L) were used for autoradiographlc studies in a series of rat brain slices, in order to determine the binding patterns as compared with that of 3H-nicotine. For physical reasons, for this comparison 125I-Nat was used. H showed autoradiographlc pattern similar to tlmt of 3H-nicotine with accumulation in cortex, hippocampus and thalanaic nuclei. With L, these structures were not identified. Conclusion: The described procedure for 1-123-1abeling of nicotine yields high specific activity. This high activity proved to be not only sufficient, but also essential to allow the compound to bind specifically to nicotinergic receptors. Monographs of radiopharmaceuticals (RP's) included in the European Pharmacopoeia (Eur.Ph.) indicate the ener~l~ for the most characteristic gamma photon in order to perfor~ the radionuclidic purity test. This test can be carried out by any suitable instrument,being the NaI(TI) detector the most used at hospital level. In the radionuclidic purity test of RP's labelled with 75Se and lllIn a sain peak over 400 keV, not defined as characteristic for these radionuclides, is obtained by using a 3" NaI(T1) through-hole type detector; this unexpected peak has a fractional count rate higher than 50% of the total count rate of the spectrum of both radionuclides. However testing the same samples by using a 2" NaI(TI) detector coupled to a 256 multichannel analyzer system the contribution from the abnormal peak tot he total count rate registered in the whole spectrum is lower (11.5% for 75Se and 3.4% for lllIn) and decreasing to negligible values when the source to detector distance is increased. These unexpected peaks are explained as an artifact due to the coincidence summing peak effect. This effect occurs with radionuclides emitting two or more cascade photons within the resolving time of the detector. The most important consecuence of this artifact is the possibility of concluding a poor radionuclidic purity for some RP's. Therefore the possibility of the sum peak effect should be advised in the Euro Ph. in the specific monographs for RP's for wich this effect is known. Separation in fractions of high cost kits is a common practice in Radiopharmacies. We have observed that good radiochemical purity (RCP) of Cardiolite cannot be obtained simply by separation in fractions and stored at -20 °C. Since, we found that after 24 hrs of dividing the RCP of the frozen aliquots was low. Moreover, the results depended on the perteclmetate activity, RCP: 86+9% with 1073_+333 MBq (n=6), 74_+8% with 2516_+444 MBq (n=3), 55_+4% with 5661_+111 MBq (n=3). These results were different from those obtained without dividing the Cardiolite and following the kit instructions, RCP:97.3 _-t-1.5 % (n = 15). Smaller quantities of the reducing agent in the aliquots, or damage when handling, could be the reason of the low RCP. Accordingly, we have studied the effect of adding Sn ÷2. The time expensive labelling process of radioactive labelled thrombocytes is a disadvantage in clinical usage. Also omitting certain steps the time i for the whole process needs more than 45 minutes. The reasons, why this process is time consuming, are the repeated centrifugation steps to separate the blood cells and the recommended low acceleration value (max. 1000 g) to avoid the damage of thrombocytes. The aim of our work was to reduce the labelling time through optimisation the steps of centrifugiation with Higher A_cceleration _Short Time (HAST)centrifugation. With short-time exeeding the recommended 1000 g and a reduced tube filling (shorter sedimentation path) we determined the possible time reducing factor and the possible damage of platelets. The blood cells from 25 ml ACD-blood was selected by a first HASTcentrifugation (3 min, 3000 U/rain, max.1500 g, 25 ml Monovette, 25 mm Diameter). The PRP was then transferred in a 50 ml tube followed by a second HAST-centrifugation (3 min, 3000 U/rain, max. 1500 g). The sedimented thrombocytes were redisperged and incubated ( 5 min, 37 °(3) with 111-1n-Oxinat. After adding of 10 ml buffer solution the labelled thrombocytes were be selected by a third HAST-centrifugation (3 rain, 3000 U/rain, max. 1500 g). The following parameters were determined: Tc-99m human serum albumin (HSA)has been used in nuclear medicine for almost 30 years. However, Tc-99m HSA is not an optimal radiopharmaceutical due to its in-vivo instability. The purpose of our study was to develop and evaluate a new method for labelling HSA, A hexadentate nitrogen-donor che]ating ligand N, N, N', N'-tetrakis (2-benzymidazolylmethyl)', 2-ethanediamine (EDTB) was synthesized by condensation of t.2-benzenediamine and ethylene-diaminete-traacetic acid (EDTA) in glycol for 20 hours followed by precipitation of the crude product with water and purification by reorystallization from hot absolute ethanol, The EDTB-HSA was prepared by mixing HSA and EDTB solutions and incubating the soluation at room temperature for 2 hours. The conjugated EDTB-HSA was separated and purified by PD-IO gel chromatography, and was a d d e d into S n ( I I ) solution, which was dispensed into vials. The labelling efficiency and in-vivo stability test of Tc-ggm EDTB-HSA were performed with ITLC. The labelling efficiency was 92.88%, The in-vivo stability was 91.19% (1 hr), 90.63% (2 hrs), 88.93% (3 hrs), 88,42~ (4 hrs) and 85.37% (B hrs), respectively.Our preliminary study revealed the quality of EDTB-HSA was superior to the currently used commercial HSA kit, and EDTB was a potential method for labelling various protein, The purpose of this investigation was to evaluate Ga-67-DTPA for the scintigraphic visualization of experimental abscesses in comparison to Ga-67 citrate. The biodistributions of both radiopharmaceuticals (RP's) were determined in mice with abscesses induced by turpentine 6 days previously in right thigh muscle. After i.v. injection of 3.7 MBq, the mice were sacrificed at 1,3, 6, and 24 h and scintigraphic images were obtained All the organs, the abscess, some muscle, blood and urine when available were obtained, weighed and counted. % uptake/g tissues and abscess/muscle (NM), blood (A/B), intestine (A/I), liver (A/L) and kidney (A/K) ratios were calculated. Normal distribution of each RP was determined after i.v. administration of 37 MBq in 3 rabbits by scintigraphic imaging up to 24 h. The abscesses were visualized with both RP's starting at 3 h. The max. A/M, A/B, A/I, A/L, and A/K ratios were 6.66+0.63 (3 h), 8.63+0.77 (3 h), 2.60+0.10 (3 h), 1.57+0.12 (6 h) and 1.20+0.36 (3 h) for Ga-67-DTPA, and 4.97+2.00 (6 h), 5.24+0.37 (24 h), 2.01+0.37 (24 h), 1.09+0.76 (6 h) and 0.914_-+0.616 (6 h) for Ga-67-citrate, respectively. On normal scintigrams of rabbits the kidneys and the urinary bladder were visualized with some blood background with Ga-67-DTPA.In conclusion, Ga-67-DTPA is preferred to Ga-67-citrate, because of higher concentration ratios attained earlier and predominant excretion via kidneys. Experimental models of myocardial perfusion study are of paramount importance to select new radiopharmaceuticals for scintigraphic imaging evaluation of coronary artery disease. Aims of this study are addressed to evaluate: a) the biodistribution comparison results of some new tracers; b) their relative myocardium retention mechanism. a) The use of myocardial perfusion agents for the detection of areas of reduced blood flow, is dependent, at least in part, upon the single pass extraction of the respective probe compound. In Tab. 1 the behaviour of some compounds at this respect is reported in a comparative way.[ b) The mechanism of cellular uptake and retention is the fundamental pattern for understanding the clinical meaning of scintigraphic images. In Tab The study of the mechanism of cellular retention of these agents, have shown that neither ]ipophilic properties nor the cathionic charge alone are sufficient to characterize the biologic properties of these complexes. Calichemicins belong to a new class of potent antitumor antibiotics which contain a polysubstituted aromatic carboxylic acid fragment. Analogs of the fragment containing iodine have been synthesized. A methylester, Methyl 4-hydroxy-5-iodo-2,3-dimethexy-6-methylbenzoate, was synthesized by van Laak and Scharf (Tetrahedron 45: 5511, 1989) , and was kindly supplied by Prof. H-D Scharf of the Institute fur Organische Chemie der RWTH Aachen, Germany. The acid fragment is released following hydrolysis of the ester. We investigated biological behavior of the two compounds using radionuclide tracer techniques. In the present study, iodine-131 was used to label the monoiodo methylester by exchange reactions (the yield was over 90%). The radioiodinated ester was then hydrolyzed to obtain the acid form retaining 1-131. Biodistribution studies in mice were carried out with these two labeled compounds. Animals were sacrificed at different times (3 and i0 min, and i, 4 and 24 hr) following intravenous injections into tail veins. Organs were obtained, and assayed for radioactivity. Tissue distributions of these two labeled compounds were entirely different. Initial uptake in the liver, kidneys and the Gl-tract was high for the ester. On the contrary, initial uptake of the labeled acid was high in the kidneys, and over 90% of radioactivity was cleared from the body in 4 hours via urinary excretion.Its biodistribution was similar to that of Tc-99m labeled DTPA, as confirmed by carrying out tracer studies in mice under similar conditions. This might be useful as a radioiodinated glomerular agent for clinical applications when interfering radionuclides are present.