Monday, 2 September 1991 Monday, 2 September 1991

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M.M. Henrich, E. Vester, F. J~licher, O. Muzik, H. H e r z o g , K. G r o B m a n n , B.E. S t r a u e r , L.E. F e i n e n d e g e n . Dept. o f N u c l e a r M e d i c i n e a n d C a r d i o l o g y , Univ. of D ~ s s e l d o r f a n d K F A J~lich, FRG

Czemin L PorentaG, B~nkcn R, Krivokapich J, SochorH, Phelps

M Y O C A R D I A L G L U C O S E M E T A B O L I S M IN P A T I E N T S W I T H A CORONARY ARTERY OCCLUSION: A FDG-P~T STUDY IN T H E F A S T E D S T A T E A N D A F T E R G L U C O S E LOAD. T h e p u r p o s e of t h i s s t u d y w a s to c o m p a r e t h e m e t a b o l i c r a t e of g l u c o s e (MRGIc) in p a t i e n t s w i t h a c h r o n i c c o r o n a r y a r t e r y o c c l u s i o n in t h e f a s t e d s t a t e and a f t e r g l u c o s e load. - T e n patients were studied using PET with N-13 ammonia and F-18 FDG after an overnight fast and 1.5 h a f t e r o r a l g l u c o s e (50g). P a r a m e t r i c images of MRGIc were calculated from dynamic F D G s t u d i e s u s i n g P a t l a k ' s l i n e a r i z a t i o n app r o a c h a l l o w i n g for i n d i v i d u a l r a t e c o n s t a n t s . S h o r t a x i s c u t s of a m m o n i a a n d M R G I c i m a g e s w e r e f u r t h e r p r o c e s s e d into a p o l a r map. - In t h e f a s t e d s t a t e two p a t i e n t s d i d n o t e x h i b i t a n y d e t e c t a b l e MRGIc. F o u r p a t i e n t s e x h i b i t e d t h e m a x i m u m of M R G I c on the b o r d e r of t h e l o w flow area (group A), another four had the m a x i m u m in n o r m a l l y p e r f u s e d r e g i o n s (group B). M R G I c w a s d e t e r m i n e d in t h e c e n t e r (I) a n d in t h e b o r d e r of t h e l o w f l o w r e g i o n s (II), a n d in n o r m a l r e g i o n s (III). [umol/min/100g] I II III gr A Fasted 9.8 + 5.0 18.2 + 5.9 9.8 + 7.4 Load 4 0 . 5 " i i 0 . 1 5 7 . 8 " i i 7 6 58 9 " i 1 2 . 0 gr B Fasted 4.6 ± 3.1 15.9 + 1 0 . 8 Load 6.8 ± 2.9 44.4"~19'6 *p
M, Schelbert H U C L A SCHOOL OF M E D I C I N E Los Angeles, CA 9 0 0 2 4 - 1 7 2 1

QUANTIFICATION OF CHANGES IN PERFUSION, METABOLISM AND FUNCTION BY PET AND 2-D ECHO IN PATIENTS WITH MYOCARDIAL INFARCTION To determine serial changes of perfusion and metabolism in myocardial segments identified as ischemic or infarcted by PET early after an infarction, 14 patients were studied within 3.5 days (r: 1-7d, PET I) and again 89 d (70-140 d, PET II) after onset of chest pain. 7 patients underwent PTCA between PET I and PET IL Dynamic PET and N-13 ammonia (2 compartment model), C-11 acetate (monoexponential fitting) and F-18 deoxyglncose (PATLAK analysis) were used to quantify myocardial blood flow (MBF), oxidative metabolism (k mono) and glucose utilization (MRGLc). Wall motion was determined by 2-D echo. Circumferential profile analysis revealed 67 normal, 14 ischemic and 17 infarcted segments at PET I. At PET ]I 10/14 ischemic segments improved to normal while four remained ischemic or deteriorated to PET infanct. 3/17 PET infarcted segments improved to ischemia, while fourteen remained unchanged. MBF, k mono/min and % MRGLc in normal segments averaged 0.851-0.25 ml/g/min, 0.065i-0.01 and 1.0i'0.10, respectively and remained unchanged at PET II. Ischemie segments demonstrated significant improvement in MBF (0.61_+0.14 ml/g/min vs 0.91i-0.3 ml/g/min) and K mono/min (0.054-1-0.012 vs 0.065) at PET II, while % MRGLc remained unchanged. However, the ratio of % MRGLc to MBF normalized from 1.7+0.7 to 1.0i-0.1 (p<0.05). MBF (0.30-!-0.15 ml/g/min), k mono/min (0.031_+0.01) and % MRGLc (38+17) were significantly reduced in infarcted segments at PET I and remained unchanged at PET II. Wall motion in ischemic segments improved significantly from PET I to PET II, but remained unchanged in PET infarcted segments. Thus, segments classified as PET ischemic early after an infarction indicate "reversible dysfunction" as demonstrated by the significant improvement of perfusion metabolism and function 3 months after the acute event.

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Czernin J, Porenta G, Brunken R, Sochor H, Phelps M, Schelbert H

L. Mortelmans, J. Nuyts, C. Schiepers, S. Vleugels, M. De Roo, F~ Van de Werf* Dept. of Nuclear Medicine and *Cardiology, U.Z. Gasthuisberg, Leuven, Belgium

U C L A S C H O O L OF M E D I C I N E Los Angeles, CA 9 0 0 2 4 - 1 7 2 1

NON-INVASIVE QUANTIFICATION OF PEP,FUSION AND METABOLISM IN MYOCARDIAL INFARCTION BY POSITRON EMISSION TOMOGRAPHY To quantify noninvasively blood flow and metabolism early after myocardial infarction (AMI) 22 patients were studied within 4 days (range: 1-Sd) after onset of chest pain. Dynamic PET and N-13 ammonia (MBF,ml/g/min, 2 compartment model), C-11 acetate (k mono/min, monoexponential fitting) and F-18 deoxyglucose (MRGLc, I/mol/g/min, modified PATLAK graphical analysis). Normal myocardium (NML), PET isehemia (ISCH, NH3J. FDG?) and PET infarction (INF, NH3$ FDG$) were defined on circumferential count profiles. A total of 103 (67%) segments were classified as NML, while 51 (33%) segments were hypoperfused. 29 (57%) hypopeffused segments were classified as INF and 22 (43%) segments as ISCH. MBF averaged 0.84!-0.20 ml/g/min in NML, was reduced to 0.57!-0.20 ml/g/min in ISCH (p<0.01) and further reduced to 0.32i-0.12 ml/g/min in INF (p<0.01 vs ISCH, p<0.001 vs NML). K mono averaged 0.063+012 in NML, was reduced in proportion to MEF in ISCH (0.055+.01, p<0.05 vs NML) and was markedly reduced in INF (0.033+0.01, p<0.01 vs ISCH, p<0.001 vs NML).Normalized MRGLe was unchanged from NML in ISCH (100 + 30 vs 100"&15%, p=NS) but reduced by 65% in INF (p<0.001 vs NML and ISCH). The ratio of %MRGLe to MBF was increased in ISCH, while it was similarly reduced in NML and INF (1.70-2-0.7 vs 1.2 5:0.30 and 1.1i-0.30, p<0.01) suggesting increased glucose extraction in ischemicaUy injured tissue. The ratio of k mono to MBF increased significantly from NML to ISCH and INF implying increased oxygen extraction in the low flow range. We conclude, that the high incidence of PET ischemia characterized by preserved glucose metabo!k rates and significant, yet moderate reduction of quantitative measurements of flow and oxidative metabolism represents a considerable amount of viable tissue within the clinical infarct zone, while PET infarction, characterized by severe and concordant reduction of flow and metabolism most likely reflects irreversibly damaged tissue.

EVALUATION OF MYOCARDIAL VIABILITY BY COMPARISON OF FDG AND MIBI POLARMAPS.

The aim of this study was to compare combined MIBI/FDG polar maps to anatomical and functional data. 8 patients treated with thrombolysis within 6 hours a f t e r an acute myocardial infarction had the following procedures IO to 14 days a f t e r onset of symptoms: coronary angiography, contrast ventriculography with isuprel stimulation (ISU), SPECT MIBI perfusion scan and PET FDG metabolic scan with a fasted protocol. The MIBI images acquired l hr post injection were processed with an automated delineation program developed at our i n s t i t u t i o n . MIBI and PET images were matched by manual adjustment and polar maps f o r both scans created. Comparing perfusion (MIBI) to metabolism (FDG) each study was v i s u a l l y interpreted as normal, match or mismatch. On the MIBI polar map a normal perfused area and the "infarcted" zone were defined using a normal data base. On the FDG map the uptake r a t i o in these areas was computed. Vessel patency was graded by TIMI score and regional wall motion (RWM) was analysed by the Sheehan method. Amelioration of RWM a f t e r isuprel stimulation (Isu +) was used as a parameter of v i a b i l i t y . Number of patients and mean FDG r a t i o are shown f o r each subgroup: NORMAL MATCH MISMATCH

Isu + 0 Q 3(I.7)

Isu I(0.8) l(O.g) 3(I.4)

TIMI(2,3) I(0.8) 0 3(1.7)

TIMI(O,I) 0 I(0.9) 3(I.4)

Combination of polar maps derived from PET FDG scans and MIBI SPECT scans provide a valuable method to evaluate myocardial v i a b i l i t y post infarction. MIBI appears an alternative to PET perfusion tracers.

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Monday, 2 September 1991

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G.Schr6ter, H.Stern, R.Bauer, N.Avril, H.R.Langhammer, K.BOhlmayer, H.W.Pabst Nuklearmedizinische Klinik und Kinderklinik, Technische Universit~t und Deutsches Herzzentrum, Minehen

P. Boureeo!s, H.R. Ham, R. Ramchurn, J. Creplet, B. Chain, M. Renard, C. Tabet and R. Bernard. Services de M4decine Nucl4aire, de Cardlologie et de Chirurgie Cardiaque, CH J. Bracops et Hop. Univ. St Pierre, Universit6 Libre de Bruxenes, Brussels, Belgium.

MYOCARDIAL ENERGY METABOLISM IN HEALTHY SUBJECTS AND PATIENTS WITH CONGENITAL OR ACQUIRED HEART DISEASE STUDIED WITH PHOSPHOROUS-31 NMR-SPECTROSCOPY (MRS)

In patients after corrective surgery for complete transposition of the great arteries by an atrial switch the morphologically right ventricle (RV) performs as the systemic ventricle. Long t e r m follow up over ten years shows a growing incidence of right ventricular failure in these patients. We i n v e s t i g a t e d 16 patients (mean age 16.3 y), who had underwent surgery more than i0 years ago (i), 4 patients with cardiomyopathy (2) (mean age 12 y) and i0 healthy volunteers (3) (mean age 17.9 y) by P-31 MRS using a 1.5 T magnet. The purpose of this study was to find out whether there were metabolic differences between the first and the two other groups. Image selective in vivo spectroscopy (ISIS) was used. The volume of interest was 61 ± 12 cm 3 . 1024 measurements were averaged, the repetition time was 3 seconds. The ratios of y-ATP/phosphocreatine(PCr) and phosphodiester(PDE)/PCr were compared. The yATP/PCr ratio in (i) was 1:2.3 ($D 0.27), in (2) 1:2.3 (SD 0.39), and in (3) 1:2.6 (SD 0.35). The PDE/PCr ratio in (2) was increased in comparision with (i) and (3). Conclusions: i. There is no difference in energy metabolism of right ventricular myocardium in patients more than I0 years after atrial switch operation, patients with cardiomyopathy, and healthy volunteers.2.Patients with cardiomyopathy show an increased PDE/PCr ratio.

DETECTION OF ISCHEMIC BUT VIABLEMYOCARDIUMIN RESTING CONDITIONS USING SPECT ANDA NOT METABOLIZED FREE FATTY ACID, THE 15-(ORTHO- 123L PHENYL)-PENTADECANOIC ACID (OPPA). The relative distributions of 123I-OPPA, 201 -thallium and 99mTc-MIBI have been compared in resting conditions and using Single Photon Emission Computed Tomography in 30 patients within the two weeks after their admission in our coronary care units for acute myocardial events (acute myocardial infarction or AMI = i9, transmural or Q+ = 17, non lransmural or Q- = 2, Thrombolysed T+ = 11 and not T- = 8, unstable angina or other CAD related situations with or without previous MI = i 1). Fifteen were submitted to revascularisation procedures (PCTA or CABG, within the three weeks after acute event) and had postoperative (within the two weeks after operation) MIBI and/or Thallium controls. Nine patients with only conservative medical treatments had MIBI control two months after acute event. Results : - marked increased OPPA uptake (upt) relative to local MIBI upt (OPPA ++ cases) has been found in 8/11 Q+T+,4/6 Q+T-, 2/2 Q-T- and 9/11 CAD. One patient Q+T+ was considered OPPA - and the last six cases exhibited differences considered as not significant (OPPA + cases) - postoperative increase of perfusion (when comparing pre and post revascularisation MIBI and/or thallium SPECT studies, two patients excluded for reason of peroperative MI) and, thus "successful revascularisation" (partial or complete) was observed in 9 OPPA ++ / 10 and 2 OPPA + / 3 in territory-ies with higher OPPA than MIBI upt. One OPPA ++ and one OPPA + exhibited no postoperative change. - only 3 (OPPA ++) of the 9 patients (7 OPPA ++, 2 OPPA +) submitted to medical treatments exhibited on their MIBI control at two months amelioration of their perfusion It is concluded that : The SPECT study and comparison of the OPPA upt relative to the MIBI distribution in resting conditions mightrepresent avery easy way to diagnoseischemic but viable tissue susceptible to benefit of revascularisation procedures in post infarction cases as well as in CAD patients (stunned, hibertinating or silent ischemic myocardium).

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K.Hohari~ J.FSldes x, Gy.A.J~noki, G.Tarj~nx, F.Varga x "FJC" Natl. Res.Inst.for Radiobiology and Radiohygiene, P.O.Box lOl H-1775 Budapest, Hungary XSemmelweis University, First Department of Hedicine, VIII. Kor~nyi S. u. 2/a, H-lOB3 Budapest Hungary PRELIMINARY CLINICAL RESULTS OF A NEW RADIOIMMUNOASSAY F0R THE HEASUREMENT OF THYROTROPIN RELEASING HORMONE (TRH)

W. BECKER. G.HORNEFF, G .R.BURMESTER, J.R.KALDEN, F.WOLF Department of Nuclear Medicine , Institute of Immunolgy and Rheumatology( Internal Medicine III) of the University of ErlangenN~irnberg, FRG

Thyrotropin Releasing Hormone (TRH) was the first hypothalamic releasing hormone to be purified and identified by Burgus et al.(1970).The value of TRH elevates in serum in the following cases:depression, in cases of low TSH, T~ and T 4 levels, further are after changes of temperature, stress etc. A new radioimmunoassay has been developed for the measurement of thyrotropin releasing hormone (TRH). The parameters of the test ere sensitivity lO0 pg/ml, intraassay CV% 5,6. We measured immunreactive TQH in serum of healthy individuals 1 to lO ng/ml.Performing a TRH-loading test/200 ug dose i.v./in euthyroid subjects a significant increase of serum TRH content could be revealed lO minutes following the intravenous injection and its serum level returned to the preload value after 50 minutes, which is in agreement with the short half-life of TRH in circulation. Based on crossreaction the assay proved to bs particularly apt for the farmaco-kinetic study of a new TRH-analogue (6 keto-piperidin-2 carbonil-L leuciI-l-1 prolinamide). Following the intravenous administration of the preparate(lO mg dose) the serum levei of the product increased remarkably, which decreased graduelly and the initial serum TRH level was attained after 6 hours. Present results do not disclose a night/daytime serum TRH level difference between euthyroid and hypothyroid subjects. Preliminary data based on our 170 measurement of 30 patient samples indicate that the new RIA is suitable for the measurement of serum TRH and also may oe a useful tool for screening TRH anaIogues.

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RESULTS OF TSH-IRMA IN DEPENDENCE OF HUMAN ANTIMOUSE ANTIBODY-TITERS Monoclonal murine antibodies are increasingly used for immunoscintigraphy anf immunotherapy. The diagnostic and therapeutic agent however is a foreign antigen, which may induce host reactivity. This may interfer with the therapeutic or diagnostic reagent in-vivo resulting in a loss of efficacy or there might be an important interference to in-vitro immunoassay detecting specific antigens utilizing murine monoclonal ant~odies. 10 patients with rheumatoid arthritis who had undergone a theraeutic trial using 14-Omg of an anti-CD4 antibody were investigated. uman antimouse antibodies(HAMAS) in 6 of them 2-3 weeks after treatment was started and reached maximal amouints of 0.8 ug/ml after a single and 2 ug/ml after a repeated treatment course. Increased HAMAS normalized after 50-100 days. The determination of HAMAS was performed with an ELISA developped in the own labaratory. In 5 of 6 patients with HAMAS of more than 0.3ug/ml showed parallelly raised values of TSH(TSH-Riagnost,BEHRING FRG).Normal TSH levels were elevate up to 12u/ml and were most pronounced after a repeated trial of the murine antibody and were detectable up to 20 weeks. Other thyroid specific parameters(fT4,fT3,TSHreceptor and peroxysomal and thyroglobulin antibodies) were normal. After preincubation of the TSH-tested sera with lOufl of murine IgG/ml over 30min the TSH values were normal in all sera. The authors conclude, that increased TSH-levels may be false positive after immunoscintigraphy or immunotherapy due to human antimouse antibodies. Elevated values normalize between 50-100 days.Preincubation with murine IgG normalizes TSH levels.

Monday, 2 September 1991

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L. Massuger, C. Thomas, M. Segers, R. Claessens, ch. Schijf, P. Kenemans, F. Corstens. University Hospital Nijmegen, The Netherlands.

S.Saranti, A.Rasidakis,M.Christoforaki,A.Leonti,Ch.Kostopoulos, M. Mavrikakis and E. Gyftaki. Department of Therapeutic Clinics,Department of Nuclear Medicine,"Alexandra" Unversity Hospital,Athens,Greece.

OV-TL 3 INDUCED ~ R E S P O N S E IN P A T I E N T S W I T H O V A R I A N CANCER. OV-TL 3 is a murine monoclonal antibody (M~) that recognizes an ovarian carcinoma-associated antigenic determinant (CA3), which is probably not shed into the circulation. Using the In-lll-labeled F(ab')~ fragments of OV-TL 3 successful imaging was obtained in patients with ovarian cancer (Massuger et al., J Nucl Med 1990; 31:1809). The curren£ study was performed to determine the human antimouse antibody (HAMA) response to the infusion with I mg OV-TL 3 F(ab')2 fragments. Thirty-three patients underwent radio irmmunos cint igr aphy after i.v. administration of 140 M B q In-lll-labelled OV-TL 3 F(ab' )z. None of the patients had received murine MAbs prior to this study. Blood samples were taken prior to the infusion and at 3 and 6 weeks postinfusion. Eased on the OV-TL 3 M~kb and its F(ab')~ fragment, we have developed five homologous and heterologous Europium-labeled HAMA assays and compared their results with those of two co~m~ercially available HAMA assays (ET I-HA/dAK, Sorin Biomedica and ImmuSTRIP HAMA, Immunomedics), the latter also after modification with OV-TL 3 F(ab')~. Seven of the patients studied were found to have a specific OV-TL 3 F(ab')~ induced HAMA response. In only two of these patients the positive response could not be suppressed by adding two n o n - i ~ u n e sera from different mouse strains, indicating the possible presence of anti-idiotypic HAMA. The heterologous assays together with the commercial assays indicated pretreatment HAMA in eight of the patients, while both commercial assays indicated positivity in a number of other serum samples. These reactions are probably not induced by the antibody infusion. Two of the patients showed a transient skin rash after antibody infusion. Both patients formed part of the group with the OV-TL 3 F(ab' )~ induced HAMA response.

THE DIAGNOSTIC VALUE OF WHOLE BLOOD HISTAMINE IN ATOPIC PATIENTS. This study w a s u n d e r t a k e n to assess the diagnostic value of plasma and whole blood histamine measurement in atopy. In 54 patients (19M and 35F, age 34.2+12.1 yrs), who had been referred for evaluation of atopic disorders, and in 23 non atopic controls (9M and 14F, age 40.OFII,I vrs) plasma and whole blood histamine levels were measured, as well as total IgE and specific antigen IgE (according to each patient clinical history). A R I A method, which combines the sample histamine acylation with monoclonal antibodies (coated tubes), was used for the plasma mud whole blood (after cell lysis) histamine determination.Patients with leucocytosis, recent infection,cancer~ parasitic and hematologic disorders were excluded from the study. Our results are as follows: IgE (kU/ml) Plasma Hist. ~qole blood (nM/ml) Hist.(nM/ml) Controls 33.~F19.3 1.3~F0.81 243 + i00 Patients 303 $289 1.43/~0.83 582 ~ 289 S t a t i s t i c a l l y significant difference was found between the patient and the controls for the total IgE and the whole blood histamine (P
FP-2G1-5

FP-2G1-6

L.I.Vinnitsk~, G.~.Smagulova, L.A.Gnilitsky, O.I.Matinyan N a t i o n a l R e s e a r c h C e n t r e of S u r g e r y , U $ S R A c a d e m y of M e d i c a l S c i e n c e s

Koutsiouba P, Go~ou L, Pozantzidou P, Natsis P, Tsialta A, Trivizaki E. Nuclear Medicine Department Metaxa Cancer Hospital of Piraeus, Greece.

CLINICAL APPLICATIONS OF NEW CA 72-% TIIMOR M A R K E R IN S T O M A C H C A R C I N O M A T h e a i m of t h e r e s e a r c h w a s t o s t u d y clinical significance of new tumor-associated m a r k e r C ~ 7 2 - ~ in d i a g n o s i s of b e n i g n a n d malignant stomach disearses. There were compared CA 72-4 v a l u e s w i t h b l o o d l e v e l s of CA 19-9, CEA, T A T I a n d ferritin. The l e v e l s of tumor markers were evaluated by radioimmnnoassay with monocloSal antibodies. The C~ 72-@ level in t h e c o n t r o l Eroup (healthy blood donors) was 1,29±0,33 U/ml an4 v a r i e d b e t w e e n 0 a n d ~ , 5 3 U / m l . In c a s e s with benign ~astric diseases 121 pts) o n l y in i pt CA 7~-% {5,3 U/ml) w a s o v e r c u t of~. Serum investigations in 51 p t s w i t h stomach carcinoma s h o w e d CA 72-~ values within 1,7-269,~ U/ml (average value was 30.3i8,9 U / m l ] . In p t s w i t h o u t m e t a s t a s e s C A 7 2 - ~ l e v e l was 5 , 6 6 ± 0 , 7 1 U / m l , a n d in p t s w i t h m e t a s t a s e s 7%,86f20,&5 U/ml. Radical surgery caused the d~crease of tumor marker levels (CAI9-9,CA72-% and CEA) practically d o w n to n o r m a l v a l u e . A t p a l l i a t i ve therapy the investigated v a l u e s r e m a i n e d at t h e s a m e h i g h l e v e l . D y n a m i c f o l l o w - u p of di~ s e a s e r m c u r r e n c i e s s h o w e d s h a r p C A 7 2 - & increa s e of o v e r 200 U/ml. The results we receive m~rkers i n d i c a t e c l i n i c a l i m p o r t a n c e c~ t u m o r complex evaluation in d i a g n o s i s , d e t e r m i n a t i o n of t u m o r p r o c e s s s t a g e , a s s e s s m e n t of s u r g i c a l treatment, and revealing of d i s e a s e recurrences.

THE CAR-3 ANTIGEN IN PATHOLOGY OF GASTROINTESTINAL TRACZ COP~EI~TIONWITH CEA, Ca 19-9, Ca 50~AND TAG-72. The clinical relevance of the new tumor marker CAR-3 was studied in 326 patients with malignancy, 59 with benign diseases of gastrointestinal tract, 77 normal subjects and 36 with other malignancies. The mean levels of AR-3 antibody were 7,2+5,gu/ml in the control group, considering less than 20uTml as normal.ln benign diseases the mean value was 7,9+--7,4 u/ml. The highest levels in the malignancies of a G.l.trsctw~re founded in pancreatic cancer(200,6~15,94 u/ml).In breas~ ovarian and head-neck cancers~AR-3 antibody was in normal range (10,6+--7,6u/ml). In malignant diseases of G.I. tract true positive test of AR-3 founded in 7/13 of patients with pancreatic cancer, in 4/19 pts. with hepatobiliary cancer, in 8/46 pts. with stomach cancer and in 46/248 with colon cancer When we compared AR-3 antibody to the other tumor markers in malignancies of G.I. tract we founded similar specificity of all the markers (92,9% - 100%), but the sensitivity was different(AR-3 48,1% vs TAG-72 53,3%, Ca 50 77,7%, Ca 19-9 79% and CEA 87,6%).In the other malignancies the sencitivity of AR-3 was low but the specificity very high. In conclusion AR-3 appears to be a tumor marker of interest in pancreatic cancer (sensit. 77,7%, specif. 100%).The combination AR-3 and Ca 19-9 shows to be the most effective to increase the sensitivity in patients with malignant diseases of G.I. tract.

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Monday, 2 September 1991

FP-2HI-1 K.KOURIS.I.D.CULLUM,P.H.JARRITT,P.J.ELL Institute of Nuclear Medicine, UCMSM, London.

GE/CGR N~GROCA_MAND SME 810 BRAIN SCANNER: A PHYSICAL COMPARISON • The GE/CGR Neurocam is a three-headed camera SPET system dedicated to multislice brain tomography. The SME 810 brain scanner is a single slice machine comprising 12 NaI detectors with highly focussed collimators. We compared the sensitivity, resolution and clinical efficacy of these systems. Using a water-filled cylinder (20cm diameter x 30cm) containing 99Tcm, the sensitivity of the Neurocam was 30.0 and 50,7 kcps/MBq/ml/cm for the HR and GP collimators respectively, and 314.7 kcps/MBq/ml/slice for the SME. TomographJc resolution was measured in air and water using 5 line sources, with 2cm spacing. For the Neurocam with HR collimator, the transaxial FWHM values in water were 9.8mm at the centre and 8.gmm at 8cm from the centre. Those for the SME were 8.1mm and 8.7mm. The average peak/valley ratio in water was 8.4 in SPET mode compared to 4.8 in planar mode. The z-axis resolution was 8.3ram for the Neurocam and 19.0mm for the SME. The physical characteristics of the Neurocam enable routine acquisition of high resolution, multislice, brain SPET data in about 14min with 99Tcm-HMPAO. Those of the SME, enable dynamic SPET studies with 123I-iBZM allowing for the observation of tracer distribution changes in a given slice.

FP-2H1-3 S.A. Larsson, S. Kimiaei, Y. Wang and Ho Jacobsson Depts of Hospital Physics and Diagnostic Radiology, Karolinska Hospital, Stockholm, Sweden

SIMULTANEOUS I~4ISSION AND TRANSMISSION COMPUI~D TCMO(~APHIC IMAGING WITH ROTATING GAMMA CAMERA In--on. Conventional SPECT images suffer from a lack of detailed anatomical information and landmarks. In addition, lung and bone tissues , have attenuation properties that are significantly different from those of soft tissue and these effects have to be carefully considered in attenuation correction routines aiming at quantitative SPECT. Method. We have developed a now technique whereby transmission and emission data can be achieved during the same regular examination procedure. A specially designed transmission source with four narrow collimated 40 cm long line-sources, is supplied with a computer-operated shutter. At each angle, emission data is first acquired with the shutter closed. Then the shutter opens and transmission (and emission) data is acquired. The fraction of emission events in the primary transmission data is subtracted before reconstructing the CT-sections. Results. Examinations are performed with about 4 GBq of 99m-Tc in the line sources giving a total count-rate of around 64 kcts/s without a patient and about 25 kcts/s with a patient in between the source and the detector. The spatial resolution of the transmission system with the LEGP-collimator is about 25 ram. Image noise (SD) i s about 8% at a transmission acquisition time of 3 s/angle (128 angles). Ccnc/usion. This technique produces a map of Cf-data, body contours and anatomical lane%harks together with the ordinary SPECT-data at the cost of 30-50% prolonged examination time. By using line-sources instead of a uniform flat-field source, better statistics is achieved at a cost of a limited n ~ of sections, without overloading the can~ra.

524

FP-2H1-2 A. Giordano, M.L. Calcagni, P. Di Fazio, E. Sada*, S. Colombo*, G. Galli. Universit~ Cattolica S.Cuore, Largo A.Gemelli 8, 0U168 Roma. *SELO, Via G.di V i t t o r i o n.307, 20099 Sesto S.Giovanni (Milano) I t a l y . BRAIN SPET (9ikaTc-HH-PAO) and DSPET (133Xe) USING A NEW FAST ROTATING, 28 SLICES CEREBRALTONOGRAPH. A new tomegraph (CER.TO.96 by SELO, Italy) capable of high resolution brain SPET as well as quantitative rCBF mapping (DSPET) is presently under investigation in our institute. The system consists of 4 compact gamB-cameras (25 cm crystal diameter) cubically arranged and supporter by a fast rotating "wobbling" gantry; a complete set of 24 planar views is collected in 5 seconds (1 rotation/20 sec.). ToBographic resolution at 13mmdepth is 8 mm (FWHN, high resolution co11.); point source sens i t i v i t y is 9200 cpm/~Ci/min (high s e n s i t i v i t y c 0 1 1 . ) . SPET using HN-PA0 or other perfusion tracers i s e a s i l y performed by standard software. 133Xe-inha]ation DSPET is performed recording 4consecutive 1 min. SPETs; rCBF tomographic slices are obtained according to the "Kanno-Lassen" method (pixels values are m1/100 gr./min. From our f i r s t clinical experiences the main advantages of the system are the availability of up to 28 rCBF slices (non interpolated) and the p o s s i b i l i t y to generate coronal, saglttel and oblique slices, thus probablY improving lesion detectability and spatial l o c a l i z a t i o n in a t r u l y q u a n t i t a t i v e format; moreover, the p e s s i b i l i t y t o perfomltN-PA0 and 133Xe brain studies in the same patient is expected to allow an easier approach to the quantification of HR-PA0 SPET.

FP-2H1-4 M.H.Bourauianon. B.J.Krause, H.Valette, H.Berrah, M.Tararine, De la Barre, B.Bendriem, G.Bourg Heckly and A.Syrota. SHFJ, Orsay and Sopha Medical, Buc, FRANCE. THE RESOLUTION OF ATTENUATION COEFFICIENTS MEASURED BY CONE BEAM TRANSMISSION. Sensitivity, spatial resolution and scatter directly influence the quantitative measure of attenuation coefficients (p). Since significant errors may result from the use of incorrect I~ values in each pixel, transmission images should have a high resolution of ~. These parameters were determined in experiments carried out with a Sophycamera DSX equipped with an obstructor and a collimated point source filled with 7 mCi of ggm-TC. Average sensitivities were measured as transmitted photons/sec x mCi x cm2 through different organs of volunteers: brain = 50, lungs = 125, mediastinum = 25, abdomen = 30. Transverse spatial resolution was measured on the edges of a 4x2.Sx15cm lucite block in air: 5.4 + 0.6 mm and on the edges of a 8x4x4cm air cavity within a scattering medium: 8.5 + 0.8 mm. Scatter was quantified in the shadow of lead shields placed in the field of view of transmission through a cylindrical phantom (diameter 20cm) and found to represent in the worst case 45% of directly transmitted counts. The resolution of p. was evaluated with a.pie phantom (diameter 20cm) filled with solutions of different densities 1.0, 1.1, 1.2 and 1.3. For three acquisition statistics the different compartments were differentiated on the reconstructed images; therefore the resolution of p. is less than 8% (ratio of 0.1/1.3)..Conclusion: Maps of attenuation coefficients, obtained by cone beam transmission using an uncollimated gamma camera, have a resolution of p. < 8%. These results should permit segmentation into well defined p. classes (e.g. blood, bone...) and internal calibration for poorly defined p. areas (e.g. lungs...).

Monday, 2 September 1991

FP-2H1-5 E.TOURNIER, J.J.CHAILLOUT, CEA-DTA LETI BP 85X, GRENOBLE, F R A N C E

FP-2HI-6 C. JANIN,

¢. M E S T A I S

AN A N T I PILE-UP S Y S T E M B Y S I G N A L D E C O N V O L U T I O N : A FEASIBILITY STUDY TO IMPROVE GAMMA-CAMERA C O U N T R A T E W I T H O U T L O S S OF S P A T I A L R E S O L U T I O N

CWJ Schiepers, MA Dahlbom, RA Hawkins, CK Hoh, TM Guerrero, EJ Hoffman, ME Phelps UCLA School of Medicine, Los Angeles, California, USA SYSTEM FOR TOTAL BODY PET OF SKELETAL AND SOFT TISSUES

g a m m a camera acts as a c o n v o l u t i o n o p e r a t o r t h a t t r a n s f o r m s t h e g a m m a ray, w h i c h is e q u i v a l e n t to a D i r a c f u n c t i o n ~ t ) , into a 1 gs l o n g e l e c t r i c p u l s e s ( t ) = 8(t) * h ( t ) . The purpose of this study is t o f i n d t h e i n v e r s e t r a n s f e r f u n c t i o n h-l(t) by w h i c h the e l e c t r i c pulse s ( t ) s h o u l d be f i l t e r e d in o r d e r to r e t u r n as c l o s e l y as p o s s i b l e to the Dirac function, 8(t) = h-l(t) * s ( t ) , thus a l l o w i n g to s e p a r a t e p r e v i o u s l y p i l e d - u p pulses. The m e t h o d we u s e d was to b u i l d a m o d e l of the g a m m a c a m e r a e l e c t r i c pulses, a n d to c o m p u t e an inverse transfer function that can separate p u l s e s as c l o s e as 600 ns w i t h an a m p l i t u d e p r e c i s i o n of 1% a n d an i n c r e a s e of t h e n o i s e s t a n d a r d d e v i a t i o n b y a f a c t o r l o w e r t h a n 3. S e v e r a l filters c o u l d m e e t t h e s e c r i t e r i o n s a n d t h e i r e f f i c i e n c y has b e e n shown b y t w o types of r e s u l t s : a t h o u s a n d e n e r g y p u l s e s w e r e acquired, w i t h o u t a n d w i t h p i l e - u p , p r o v i d i n g an e n e r g y spectrum resolution o f 11% a n d 15%. A f t e r filtering the same electric pulses by the inverse transfer function, the energy resolution was r e s p e c t i v e l y 11% (no l o s s of s p a t i a l resolution) a n d 12% (thus d o u b l i n g the count rate). The f e a s i b i l i t y and e f f i c i e n c y of the signal deconvolution technique has been shown and can be easily implemented by e l e c t r o n i c hardware.

A method was developed f o r total body imaging on the Siemens 931/08 tomograph. This system has a f i e l d of view of 101.25 mm and an axial sampling distance of 6.75 mm; with interlacing reduced to 3.375 mm. Data were acquired as sinograms, normalized, decay corrected and resorted into 2-D projection images. These images were' reviewed in a continuous loop display adding a 3-D appearance. The images were also reconstructed in transaxial and 81 cm long coronal and sagittal body views f o r detailed, high contrast review. Skeletal imaging was performed with 18F-, and soft tissue imaging with 18F-FDG. Ten male volunteers were studied and lO patients with various tumors. A dose of 370 MBq was administered and imaging begun a f t e r a 30-90 min delay. Total imaging time varied from l to 2 hrs. High quality images were obtained, both f o r tomographic and projection imaging. Contrast between bones and soft-tissues was high. Skeletal and soft-tissue images were "complementary", with "sparing" of the bones in soft tissue images and vice versa. PET detected metastases that were not seen on the regular MDP bone scan, radiograph or CT. Tumors showed d i f f e r e n t f l u o r i d e uptake and glucose u t i l i z a t i o n , related to t h e i r aggressiveness. 2 min acquisitions per plane appeared s u f f i c i e n t f o r a high image quality. Dynamic imaging allows quantitative analysis of the uptake in various tissues. With an appropriate model, absolute bone turnover or glucose u t i l i z a t i o n can be calculated, a u t i l i t y with excellent future perspective f o r studying generalized bone disorders and focal pathology. A method f o r calculated attenuation correction of the 81 cm total body acquisitions is presently being implemented.

FP-211-1

FP-211-2

G. Bormans, A. Janssen, P. Adriaens, D. Crombez, A. Witsenboer, J. De Goeij, M. De Roo and A. Verbruggen. Radiopharm. and Nucl. Medicine U.Z. Gasthuisberg K.U.Leuven, Belgium and Cygne B.V., Eindhoven, The Netherlands.

C. LOC'H R. CANTINEAU*, M. GUILLAUME*, ~I~,E. Service Hospitalier Fr6d6ric Joliot, DRIPP-CEA, F-91401 ORSAY Cedex, F~L~NCE, * Cyclotron Research Center, B-4000 LIEGE, BELGIQUE

A

h(t)

AN IMPROVED ZINC-62/COPPER-62 GENERATOR FOR THE PRODUCTION OF 62Cu-PTSM 62Cu-pyruvaldehyde bisfN-methylthiosemicarhazone) [62CuPTSM] has shown potential as a generator produced radiopharmaceutieal for the measurement of heart, brain and kidney perfusion ~hy PET: The gene2rator types and labelling procedures reported for e production of Cu-PTSM are both complex and time consuming. This limits their practical usefulness in daily practice in view of the short half-life of 62Cu (9.73 min). We have now developed (a) an improved generator system based on a small (25mm x 5ram) Dowex lx16, 200-400 mesh ion exchange column and Co) a faster preparation method for 62CuPTSM. The parent radionuclide 62Zn i s produced by irradiation of a natural copper target with 26 MeV protons. 62Zn is separated from the Cu bulk by a semi-automated procedure on a Dowex lx8, 200-400 mesh column (60mm x 10mm) and loaded on the generator column. H2PTSM was synthesized following a described procedure. The generator column is eluted with 1 ml of a solution that is 1.7 molar in NaC1 and 0.1 molar in HC1. The ehiate, containing typically 370-740 MBq 62Cu, is filtered on-line through a sterile 0.22 #m filter and collected in a sterile vial containing 125 /~g H2PTSM, 100/~1 EtOH and 1.9 ml 0.25M NaOAc. The 62CuPTSM is instantly formed and has a radiochemical purity >99% as assessed by RP-HPLC. The zinc-62 breakthrough on the generator column after 20 elutions is less than 10-5 of the amount of 62Cu. The small volume of the generator column allows to limit the elution volume to 1 ml without affecting the radionuclidic purity or the elution efficiency ( > 80%). This new production method of 62Cu-PTSM recluires a preparation time less than 30 seconds and yields a solution with high radiochemical purity that can readily be injected intravenously. This approach obviates the time consuming solid phase extraction step proposed by other authors.

PREPARATION OF 76Br-BROMOTROPRAPRIDE, A NEW DOPAMINE D2 RECEPTOR LIGAND FOR PET STUDIES. Troprapride, a nortroprane substituted benzamide antagonist, and its halogenated derivatives, possess high affimty and selectivity for central dopamine D2 receptors. lodotroprapride has been labelled with 1251 for in vitro studies and 1231 for SPECT imaging of D2 receptors (CANTINEAU et al, 1990). For PET studies 76Br-Bromotroprapride has been prepared by nucleophilic substitution of the iodinated analog. The exchange between 76Br (non carrier added 76BrNH4) and cold iodine occurs in 30 rain at 180°C in a sealed vial in presence of Cu÷ and of an excess of reducing agents ([[entisic acid, ascorbic acid, citric acid). For purification, the reaction mixture is poured on a C18 cartridge and polar products are washed with water. Halogeno derivatives of troprapride are eluted with methanol and finally 76Br-Bromotroprapride is separated from the iodo precusor by HPLC on a #-Bondapak C18 column. The recording of UV (254nm) and radioactivity measurements permits the recovery of 76Br-Bromotroprapdde which is eluted before the precursor (selectivity = 1.23). The overall radiochemical preparation yield is 50%. The high specific actwity of the radioligand (20-100 MBq/nmol) and the radiochemical purity ( > 98 %) allow 76Br-Bromotroprapride to be characterized in vivo by PET in baboon. R. Cantineau et al, Proc. 8th Int. Symp. on Radiopharmaceutical Chemistry, (1990)

525

i~iiii!i!ii~ii!!iii~ii! ii~i!i!ili!iii!iiii~ii

Monday, 2 September 1991

FP-211-3

FP-211-4

Damhaut P., Cantineau R., Lemaire C., Plenevaux A., Christiaens L., Guillaume M. Cyclotron Research Center - Liege University - B30 Sad Tilman B-4000 Liege - Belgium

S. Guhlke, A. Biedermann, H.H. Coenen, G. St6cklin, P. Oehr* Institut ffir Chemie I, Forschungszentrum Jfilich; *Institut ffir Nuklearmedizin, Universit~t Bonn, FRG

2- AND 4-[18F]FLUOROTROPAPRIDE, TWO SPECIFIC D2 RECEPTOR LIGANDS FOR PET This paper reports the synthesis of two [18F]analogs of tropapride, a D2 receptor antagonist already labeled with iodine for SPECT investigations. The general synthetic procedure consists of a reductive amination of a secondary amine with [18F]fluorobenzaldehyde ' The 4-[18F]fluorobenzaldehyde is obtained from 4trimethylammoniumbenzaldehyde triflate. The aromatic nucleophilie substitution proceeds in DMSO at 80°C in presence of Kryptofix 222 and K2CO3. The 2-[ 18F]fluorobenzaidehyde is generated from the nitroprecursor by heating at 140°C. The reductive amination takes place at 120°C in the same vial after addition of norbenzyltropapride, sodium cyanoborohydride and acetic acid. The labeled compounds are purified using C18 Sep-Pak cartridges and HPLC. In both cases, the radiopharmaceuticals are obtained within 120 minutes with an overall yield of 15% (EOB) and a specific activity higher than 500 mCi/p.mole (EOS). 3 hours after injection, the 4-[18F]fluoro analog shows striatum to cerebellum and frontal cortex to cerebellum ratios of 45+5 and 1.6_+0.2 respectively. The percentage of injected dose per gram of brain is 0.5%. Biodistribution studies are in progress to evaluate the usefulness of the ortho derivative. The more attractive radiopharmaceutical will be used for human imaging of the dopaminergic D2 sites with PET.

18F-LABELLING OF BIOTIN V I A PROSTHETIC GROUPS FOR TUMOR S C I N T I G R A P H Y W I T H PET Rapid scintigraphy of tumors within 30 minutes is possible with labelled Biotin based upon its high affinity to Avidin [Oehr et al., Nucl. Med. 29, A44 (1990)]. In order to obtain a tracer for PET studies Biotin was radiolabelled w i t h fluorine-18 ( T ½ = 110 min) via prosthetic groups since uirect nucleophilic substitution was not possible. In the first case, N-2-[18F]fluoropropionyl-N'-bio tinylhydrazine could be prepared with 40±3 % radiochemical yield by a modified fluoroacylation procedure [Block et al.. JLCR 25, 185 (1987)]. No-carrier-added 2 - [ 1 8 F ] f l u o ~ propionic acid was prepared from the 2-bromopropionic acid methylester by aminopolyether (2.2.2.) activated substitution and hydrolysis. It was subsequently condensed with Biotinhydrazide b~. dicyclohexylcarbo2-[~°F]fluoro-4-methoxy diimide. Further, benzaldehyde-Biotin-hydrazone was obtained with 48±5 % radiochemical yield by reaction of the aldehyde w i t h Biotin hydrazide. The benzaldehyde precursor was also labelled by 2.2.2. activated substitution with n.c.a. 18F-. For beth laF-labelled analogues of Biotin a biological activity of > 95 % was found as shown by gel-exclusion-chromatography after complexation with Avidin. In vivo experiments with tumor bearing rats are presently being performed.

FP-211-5

FP-211-6

C.Halldin, C-G. Swahn, L. Farde, J-E. Litton and G. Sedvall. Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden.

G. Bormans, D. Crombez, M. De Roo and A. Verbruggen. Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

DETERMINATION OF (IIc)SCH 23390 AND ITS RADIOACTIVE METABOLITES IN PLASMA BY HPLC. In PET studies knowledge of the fraction of radioactivity in plasma representing unchanged tracer is essential for the calculation of the arterial plasma input curve. The dopamine D-I receptor antagonist, SCH 23390 ((R)-(+)-8chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-iH3-benzazepin-7-ol) labelled with IIc was injected intravenously into human subjects in connection with positron emission tomography (PET). Measurements of unchanged (IIc)SCH 23390 and its radioactive metabolites in plasma using high performance liquid chromatography (HPLC) was performed. A specially designed HPLCprocedure was developed. Experiments showed that >98% of the radioactivity in plasma was recovered from the column. The results show that (IIc)SCH 23390 is extensively metabolized during the one hour time span of a PET experiment (40% after 4 min and 85% after 42 min). Of the two labelled metabolites formed during the time span of the PET experiment, one has been identified as the sulphate. The HPLC system described can be applied to the analysis of a variety of labelled compounds with only a minor variation in the HPLC gradient system.

526

DEVELOPMENT OF AN EFFICIENT HPLC SYSTEM FOR THE ANALYSIS OF 2-[18F]-FDG

2-[18F]-Fluoro-2-deoxy-D-glucose (FDG) is used for the measurement of glucose metabolism and is currently the most intensively employed radiopharmaceutieal in PET. FDG is now generally prepared by the [18F]F- displacement of the 2-triflate ester of tetra-Oacetyl-g-mannose in the presence of Kryptofix 222 followed by acid hydrolysis of the ester groups. Potential radiochemieal impurities in FDG preparations are therefore 18F-fluoride and 18Flabelled O-acetyl derivatives of FDG, originating from incomplete hydrolysis. TLC provides a simple and rapid method for the radiochemical analysis of FDG but has a relatively low resolution. Published HPLC procedures for the analysis of FDG furnish incomplete information as [18F]-fluoride remains adsorbed on the HPLC column and thus cannot be quantified. In order to overcome these problems and shortcomings we have now developed an new HPLC analysis method . The mobile phase is modified in such a way that [18F]-fluoride is elated from the column after the other compounds. This analysis is achieved on a carbohydrate NH 2column (Alltech) eluted with ternary gradient mixtures of CH3CN, H20 and 0.1M NaF (Table). Time (min) 0 CH3CN(% ) 95 H20(% ) 5 NaF0.1M(%) 0

5 7.5 20 20.1 25 50 0 0 0 0 50 0 0 100 100 0 100 100 0 0

Unlike published HPLC method, this procedure enables the separation and quantification of FDG and its possible impurities including fluoride. FDG, tetra-O-acetyl-FDG and F- are all recovered from the HPLC column with excellent yields (>95 %) and show a specific retention time. Therefore this HPLC method can also be used to prove the radiochemieal identity of [18F]-fluoride.

Monday, 2 S e p t e m b e r 1991

FP-2D2-1 RM. John. P. Taggart, P. Sutton, D. Costa, P. J. Ell, H. Swanton. The Middlesex Hospital and UCMSM, London, U.K. THE ISCHAEMICCOMPONENTOF DIPYRIDAMOLEMYOCARDIAL PERFUSIONSCINTIGRAPHY: DEFINITIONUSINGA LOCAL ELECTROPHYSIOLOGICCORRELATE OF ISCHAEMIA. Although myocardial perfusion scintigraphy using pharmacological vasodilation allows detection of coronary stenoses, the exact incidence and severity of myocardial ischaemia provoked remains unclear. Accordingly, we used endocardial recordings of the monophasic action potential (MAP) as a measure of local ischaemia during dipyridamole perfusion imaging. The duration of the MAP shortens in response to ischaemia. Following routine coronary angiography, MAP recordings were obtained from the left and/or right ventricular endocardium in 31 patients (50 recording sites) during i.v. infusion of dipyridamole (0.015 mg/kg/min X 4 minutes). Head rate was held constant with atrial pacing at 20% above the patient's resting rate, Tc-99m-MIBI was administered 4 minutes after dipyridamole for subsequent SPET imaging. Shortening of the MAP . duration was apparent in 18 of the 20 recordings from areas of abnormal per'fusion. Mean (+SEM) values for alteration in MAP duration between control and peak effect at 8 minutes were 276,5(5.3) to 274.5(5.4)ms in for 30 recordings from normally perfused areas(pL-NS), 289.6(4.7) to 278.4(4.8) ms for 10 recordings from areas with abnormal perfusion but without angiographic collateral supply (p<0.002) and 269.6(5.8) to 242(4.4) ms for abnormally perfused but collateralised areas(p<0.0001). ST segment shift in the ECG was evident in only 8 of 29 patients with significant coronary stenoses; these 8 patients had collateralised viable areas of myocardium These data provide strong evidence for ischaemia being an integral component of coronary vasodilator perlusion scintigraphy. Ischaemia is of greater intensity and more likely to be overt when myocardial viability is dependent on collateral circulation.

FP-2D2-2 P Fioretti, A Mc Neill, T Slagboom, A Salustri, M Pozzoli, F de Haan, A Reijs, J Roelandt. Thoraxcenter and Department of Nuclear Medicine, Erasmus University, Rotterdam, The Netherlands. RELATIONSHIP BETWEEN MIBI-SPECTPERFUSlON DEFECTS, ANGINA AND ST DEPRESSION DURING HIGH DOSE DIPYRIDAMOLE INFUSION EARLY AFTER ACUTE INFARCTION. To assess the relationship between ST segment depression, angina and transient perfusion defects assessed by scintigraphy using 99-m Technetium MIBI SPECT following dipyridamole (D) infusion, the test was performed in 106 patients (pts) after myocardial infarction (MI), 75% within 8 days of MI. D was infused in a dose of 0.84 m g / k g over 6 minutes (min) with continuous ECG monitoring and 12 lead ECG recording each rain until 10 min after the end of D. ST depression > l m m 80 ms after the J point was considered positive for isc-haemia. MIBI (370 MBq) was injected 2 min after D ended and stress SPECT images were acquired 1 hour later. Resting studies were acquired after the same dose >24 hours apart from stress. SPECT images were scored by semi-quantitative visual analysis (47 segments, 5 points score). There were no complications from D. In 56 pts (53%), SPECT was positive for transient perfusion defects. During D, 18/56 (32%) pts with positive SPECT and 12/50 (24%) pts with negative SPECT had angina and 14/52 (27%) pts with positive SPECT and 10/49 (20%) pts with negative SPECT had ST depression (5 pts' ECG's were not interpretable). In pts with positive SPECT, mean(SD) ischaemia severity index tended to be higher in patients with ST depression compared with those without: 16.9(12.2) vs 11.5(9.5), and was also higher in pts with angina compared with those without: 17.7(14.0) vs 11.6(9.2) (p=0.06). Thus, angina and ST segment depression are equally distributed in pts with/without transient perfusion defects on SPECT. Early after MI, of 53% pts who have reversible defects on SPECT, those who develop ST depression or angina during D tend to have more severe 'ischaemia'.

FP-2D2-3

FP-2D2-4

DJ Pennell SR Underwood, RH Swanton, JM Walker, PJ Ell. Nuclear Medicine and Cardiology Departments, Middlesex Hospital, Mortimer Street, London, WIN 8AA, UK.

R. Amir, Binon

DOBLITAMI]qE THALLIUM MYOCARDIAL PERFUSION TOMfN3RAPHY

Many factors may prevent a patient performing adequately during exercise testing. Whilst dipyridamole induced coronary arterial dilation serves as a good alternative during thallium myocardial perfusion imaging, it is difficult to relate abnormalities to levels of exercise achieved in every day life. Other problems are its variable duration of action and the side effects of peripheral vasodilation. We have therefore examined the use of dobutamine for the manipulation of myocardial oxygen demand in the assessment of coronary artery disease (CAD) by thallium myocardial perfusion tomography. We studied 50 patients with angina and abnormal exercise electrocardiograms prior to coronary arteriography. Dobutamine was infused in increasing doses from 5-20 I~g/kg/min until symptoms. Thallium tomograms were acquired immediately and four hours later. Forty patients had significant CAD of whom 39 (sensitivity 97%) had abnormal thallium tomograms with a specificity of 80% which was significantly superior to exercise electrocardiography (sensitivity 78%, specificity 44%, p<0.01). Sensitivity for left anterior descending, right coronary and left circumflex lesions was 92%, 91% and 83%. There was a significant relationship between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6.0 segments in 0, 1, 2, and 3 vessel disease respectively, p<0.001). Dobutamine increased the systolic blood pressure and the heart rate, with a mean increase of 107% in the double product at 20 I~g/kg/min. The tolerated dobutamine dose was significantly correlated with the treadmill exercise time (p<0.001). No important dysrhythmias were seen. Dobutamine is a safe and well tolerated agent for the manipulation of myocardial oxygen demand. It is highly effective for the assessment of myocardial perfusion in patients with CAD. The relationship between the achieved dose and treadmill exercise performance increases its value in the clinical assessment of patients with chest pain.

E. Delcourt,

C.H.U. A. V E S A L E

W. Kostucki,

M.Guillaume,

J.P.

6110 M o n t i g n y le Tilleul, B E L G I U M

M I B I - S P E C T (MS) AND T W O - D I M E N S I O N A L E C H O C A R D I O G R A P H Y (2DE) F O L L O W I N G D O B U T A M I N E S T I M U L A T I O N IN THE A S S E S S M E N T OF C O R O N A R Y A R T E R Y D I S E A S E (CAD) T h e p o t e n t i a l u s e f u l n e s s of b o t h s t r e s s d o b u t a m i n e MS and 2DE in p r e d i c t i n g the extent and location of CAD w a s e v a l u a t e d in 35 c o n s e c u t i v e p a t i e n t s w i t h documented coronary angiography, ii of t h e m had m y o c a r d i a l i n f a r c t i o n (MI). In all patients, the two t e s t s w e r e s i m u l t a n e o u s l y performed. E c h o c a r d i o g r a m s were" a n a l y z e d in b a s a l s t a t e and after d o b u t a m i n e infusion at i n c r e a s i n g doses up to 40 ug/ Kg/ min. 740 M B q M I B I - T c - 9 9 m was a d m i n i s t e r e d at the end of the 2DE test. 2DE p o s i t i v e r e s p o n s e w a s d e f i n e d as an a b n o r m a l wall m o t i o n and r e d u c e d m y o c a r d i a l t h i c k e n i n g o c c u r ring in m y o c a r d i a l segment (s) d u r i n g d o b u t a m i n e inf u s i o n by r e f e r e n c e to the basal conditions. In p a t i e n t s w i t h o u t MI, the overall s e n s i t i v i t y for CAD was 86 % for MS and 77% for 2DE. I n d i v i d u a l a s s e s s m e n t of c o r o n a r y a r t e r y l e s i o n s s h o w e d f o l l o w i n g results: LAD Cx RCA sensitivity

77 %

77 %

specificity

70 %

90 %

69 % 90 %

sensitivity

69 %

44 %

46 %

MS

2DE specificity 90 % i00 % i00 % In p a t i e n t s w i t h MI, n o p o s i t i v e r e s p o n s e was obs e r v e d o u t s i d e t h e i n f a r c t zone b y 2DE in 8/9 of c a s e s w i t h o u t m u l t i v e s s e l CAD ( s p e c i f i c i t y : 88 %) and no r e s i d u a l i s c h a e m i a w a s f a l s e l y e v i d e n c e d by MS in these patients, the area of necrosis was ident i c a l l y located b y both techniques. The d o b u t a m i n e stress t e s t i n g at i n c r e a s i n g doses is a f e a s i b l e a n d w e l l t o l e r a t e d s t r e s s in any c o n d i tion. It s e e m s an a l t e r n a t i v e to o t h e r w e l l k n o w n stress methods in t h e a s s e s s m e n t of CAD, part i c u l a r l y in p a t i e n t s w i t h MI. T h e c o r r e l a t i o n b e t w e e n MS and 2DE in d e t e c t i o n of i s c h a e m i a at s o m e t h r e s h o l d s h o u l d be s t u d i e d in m o r e c o m p l e x c l i n i c a l conditions.

527

Monday, 2 September 1991

FP-2D2-5 A. Abreu, J.J. Mahmadan, S. Nishimura, M.S. Verani, Section of Cardiology, Baylor College of Medicine/The Methodist Hospital, Houston, Texas ADENOSINE THALLIUM-201 MYOCARDIAL SCINTIGRAPHY FOR RISK STRATIFICATION IN THE EARLY PHASE OF ACUTE MYOCARDIALINFARCTION Early detection of stress-induced myocardial perfusion defects (PD) early after acute myocardial infarction (AMI) is prognostically important. Recently, we have proposed adenosine (AD) as a potent pharmacologic stress. To evaluate the safety of this stress in the early AMI setting, we studied 125 patients (pts) with AMI (5.2+2.8 days) undergoing thallium-201 (TI-201) tomography (SPECT) during a graded infusion of AD (50, 75, 100, 140 #g/kg/min). The AMI pts were compared to a cohort of 482 other pts without AMI undergoing AD TI-201 scintigraphy. Side effects were equally frequent in pts with and without AMI (77.5% vs 80.6%, p=NS). There were no significant differences in flushing (38% vs 34%), headache (16% vs 22%), dyspnea (22% vs 18%), severe hypotension (0 vs 0.6%) and 2nd degree AV block (3.2 vs 3.7%). No patient in either group had 3rd degree AV block. Chest pain (CP) during AD infusion, however, was less frequent in pts with than in those without AMI (22% vs 37%, p<0.05). CP was usually mild and required reduction of the infusion in only 2 cases. PD in pts with CP occurred in 96.4% of AMI pts (redistribution in 61%) and in 41% of no AMI pts (redistribution in 36°/0, p<0.001). ST depression occurred with similar frequency among pts with and without AMI (14% vs 12%, p=NS). In AMI pts with ST depression, PD occurred in 100%, with redistribution in 59%, vs 64% PD and 59°/0 redistribution in pts without AMI (p<0.05). No serious complications occurred. In conclusion, AD-induced transient PD were frequently detected in pts early post AMI. AD infusion proved to be extremely safe during the early phase of AMI. These data suggest that AD TI-201 SPECT may be a valuable means for risk stratification early after AMI.

FP-2D2-6 H.Namura,H.Yamabe,T.Kakimoto,Y.Hashimoto, Y.Yasaka,K.Itoh,K.Maeda,M.Yokoyama, First Internal Medicine Kobe University S c h o o l of M e d i c i n e , K o b e , J a p a n M E C H A N I S M OF N E G A T I V E W A S H O U T R A T E B Y E X E R C I S E THALLIUM-201 SINGLE P~OTON EMISSION TOMOGRAPHY IN T H E A N G I N A L S Y N D R O M E : C O M P A R I S O N WITH THE RESPONSE AGAINST INTRACORONARY ACETYLCHOLINE ADMINISTRATION To u n m a s k t h e m e c h a n i s m o f n e g a t i v e e x e r c i s e t h a l l i u m w a s h o u t r a t e ( W R ) o f t e n i d e n t i f i e d in anginal syndrome,total 37 p a t i e n t s w i t h a t y p i cal chest pain but normal coronary arteries were recruited.Both selective intracoronary acetylcholine administration(Ach)and exercise thallium testing(ES)were p e r f o r m e d . Of t h e 25 patients(GroupA;G-A)with vasosapsm(VS)against Ach, 1 9 ( 7 6 % ) d e m o n s t r a t e d transient defect by ES, on t h e c o n t r a r y , 7 of 12 ( 5 8 % ) G - B w h o h a d no VS v e s s e l s . N e g a t i v e WR(initial minus delayed/ initial counts)were o b s e r v e d 12 of G - A ( 4 8 % ) b u t o n l y o n e ( 8 % ) in G - B . L e f t v e n t r i c u l a r zones with n e g a t i v e W R w e r e m o r e o f t e n t e r r i t o r i e d by diffuse(more than one coronary segments)VS vessels than local(localized within one coron a r y s e g m e n t ) ( 1 0 / 1 2 vs 2 / 1 2 p < . 0 5 ) . A l l 7 of G - B p o s i t i v e ES p a t i e n t s w e r e a c c o m p a n i e d b y chest discomfort and/or ST-T changes during Ach.These data suggest that(1)exercise induced i s c h e m i a in a n g i n a l s y n d r o m e m a y h a v e a s s o ciation with hyperresponse a g a i n s t A c h in s m a l l c o r o n a r y a r t e r i e s , ( 2 ) d i f f u s e VS m a y h a v e a c t s o n n e g a t i v e WR.

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~[.M.H.de Klerkl, B.A.Zonnenbergl,p.P.van Rijkl, A.D.van het Schip 1, A.van Dijkl, J.M.S.P.Quirijnenl and WJ.M.Looman2 Department of Nuclear Medicine, University Hospital Utrechtl Mallinckrodt Diagnostica B.V. 2, Petten, The Netherlands

V J LEWINGTON, P.M QUILTY, D KIRK, J M RUSSELL, N S REED D P DEARNALEY, J J BOLGER

TREATMENT OF METASTATIC BONE PAIN IN PATIENTS WITH BREAST OR PROSTATE CANCER WITH Re-186-tiEDP. PRELIMINARY RESULTS

IS STRONTIUM-B9 AN EFFECTIVE ALTERNATIVE TO RADIOTHERAPY FOR PROSTATIC METASTASES? Strontium-89 (Sr-89) is an effective treatment for metastatic bone pain in prostatic carcinoma. This study compares the efficacy of Sr-89 with radiotherapy (RT). Patients were stratified according to suitability for local or wide field radiotherapy and then randomised to receive either 200 MBq Sr-89 or RT. Response was assessed after 3 months. Crossover to the alternative therapy was an option if treatment failed.

Metastatic involvement of the skeleton is common in patients with breast or prostate cancer. The most frequent symptom associated with bone metastases is pain. We conducted a phase I dose escalation study using rhenium- 186-HEDP (Mallinckrodt Medical, Inc., USA). Ten prostate cancer patients (mean age : 67 yr) and four breast cancer patients (mean age : 46 yr) were treated with 1295 or 1850 MBq Re-186-HEDP. All patients had failed prior hormonal therapy and/or chemotherapy and were suffering from metastatic bone pain. Twelve patients (86%) experienced pain relief, which was complete in six (43%). The duration of this relief varied from 2 to more than 10 weeks (mean : 6 weeks). In 5 patients there was a transient increase in pain (flare reaction) occurring within 72 hours after injection, which subsided within 24-48 hours. There was a reversible significant decrease of the mean thrombocyte (p < 0.01) and the mean leucocyte count (p < 0.01) after rhenium therapy. This occurred in the fourth and fifth week respectively. There was no change in either renal function or in the fiver enzymes, except in case of liver metastases. Urinalysis (9 patients) showed that 65 5-14% of the injected dose was excreted in the urine. This amount depended on the fraction of the skeleton showing scintigrafic evidence of metastases. In the f'wst 24 hours 71 5- 3% of the total amount was excreted. Our first results indicate that Re-186-HEDP is an effective palliative treatment for painful bone metastases. It can safely be used in doses up to 1850 MBq. Further studies for the determination of the maximum tolerated dose are in progress.

528

Department of Nuclear Medicine Southampton General Hospital AND associated centres

114 patients were treated (59 Sr-89, 55 RT) of whom 27 died during the 3 month assessment period (7 Sr-89, 20 RT). 54% of evaluable patients reported pain relief at the original site(s) after Sr-89 compared with 33% after RT (local and wide field data pooled) (NS). 40% of patients who benefitted from Sr-89 did not develop any new sites of pain during the follow up period, compared with only 17% of those who had initially responded to RT (pooled result) (p
Monday, 2 September 1991

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FP-2G2-4

K . B u c h a l i , M . H a e s n e r , H. Lips, G . J . B e y e r , F . R 6 s c h , V. P i n k N u k l e a r m e d . K l i n i k , Med. F a k u l t . ( C h a r i t ~ ) , Humboldt-Univ. Berlin; Kern?orsch.zentr. Roasen dorf

M. O d a v i d , D. M a n o j l o v i d , V. D a n g u b i d , R. Spaid, J. K o v a ~ e v i d , a n d Z. ~uk. I n s t i t u t e of N u c l e a r M e d i c i n e M.M.A. C r n o t r a v s k a Str. 17, 11000 B E O G R A D (Yugoslavia)

89-SR VS. gO~Y-CITRATE FOR PALLIATION OF SKELETAL METASTASES. PRELIMINARY RESULTS OF A CONTROLLED STUDY The s t u d y was d e s i g n e d t o compare t h e r a p e u t i c a l e £ f i c a c y o? both n u c l i d e s in the l i g h t o? increasing restrictions to the use o? l o n g e r l i v i n g n u c l i d e s in m e d i c i n e . Up t o now, 17 B a t s . w i t h s k e l e t a l metastases o? p r o s t a t i c cancer were t r e a t e d w i t h 225 MBq Sr ( n = 7 ) , o r 1110 MBq Y (n=lO) in 3 i n j e c t i o m Pats. were s e l e c t e d by random. Therapy was

8 9 - S r M E T A S T R O N IN P A L L I A T I O N OF P A T I E N T S W I T H METASTATIC BONE PAIN NOT COUSED BY BREAST OR PROSTATIC CARCINOMA 50 pts w i t h p a i n f u l b o n e m e t a s t a s e s s e c o n d a r y to a d v a n c e d p r o s t a t i c (20) b r e a s t (6), l u n g (14) c o l o r e c t a l (7), a n d k i d n e y (3) cancer, r e s i s t a n t to a l l o t h e r a n a l g e t i c m e d i c a t i o n s a n d r a d i o t h e rapeutic procedures were treated. Therapeutic d o s e of 8 9 - S r c h l o r i d e (Metastron, A m e r s h a m Int) w a s 1,5 M B q / k g ; 18 pts w e r e r e t r e a t e d w i t h 2 or 3 doses. As w e expect, 50% pts w i t h p r o s t a t i c c a n c e r h a d d r a m a t i c i m p r o v e m e n t , 25% s u b s t a n t i al i m p r o v e m e n t , 10% some i m p r o v e m e n t , a n d o n l y 15% h a d no i m p r o v e m e n t . S i m i l a r e f f e c t s w e r e a c h i e v e d in pts w i t h b r e a s t c a r c i n o m a . In pts w i t h l u n g m e t a s t a t i c c a n c e r 21% b e c o m e p a i n - f r e e a f t e r o n e dose, 35% h a d s u b s t a n t i a l , 43% s o m e i m p r o v e m e n t s , a n d no e f f e c t s in o n e p t s only. In pts w i t h c o l e r e c t a l c a n c e r d r a m a t i c or s u b s t a n t i a l i m p r o v e m e n t w a s a c h i e v e d in 57%, a n d no eff e c t in the rest. It c o u l d be c o n c l u d e d t h a t 8 9 - S r is a u s e f u l p a l l i a t i v e a g e n t n o t o n l y in pts w i t h b r e a s t a n d p r o s t a t i c c a r c i n o m a s , b u t a l s o in cases in f i n a l s t a g e of o t h e r t y p e s of malignancy. There was no significant haematological toxicity. The therapeutic efficacy was c o n s i s t e n t w i t h the s p r e a d and m a s s of o s s e o u s metastases.

i n t e r r u p t e d d u e to m a r r o w d e p r e s s i o n in 4 (Y). P a r t i a l r e l i e f o £ p a i n s o c c u r r e d in 5 0 ~ ? o r b o t h S r a n d Y. 3 / 7 (Sr), a n d 7 / 1 0 (Y) a r e a l i v e up to 21 me. M e a n s u r v i v a l is 7 (Sr), a n d 11 m o n t h s (Y) NOW.

Bone marrow depression, at l e a s t garde I WHO, occurred in 0/5 (Sr), and 8/9 (Y). Dose calculations at the metastatic s i t e p o i n t to a r a t i o o£ 5, met by the a c t i v i t y applied. But, marrow dose increases to a ratio of 1/15 ( S t / Y ) . In s p i t e o? increased marrow t o x i c i t y 90-Y reveals equal or b e t t e r r e s u l t s .

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S. Vallabhajosula, M. Chinol, S.J. Goldsmith, Mount Sinai Medical Center, New York, NY & K. Deutsch, L. Chinen and E.A. Deutsch, Mallinckrodt Medical Inc., St. Louis, Me, USA.

P.Oehr, U . W a g n e r , B . B r i e l e , A . H o t z e , S . S c h m i d t , J . R e i n s b e r g , Q.Liu, Y.Ota, D . K r e b s and H . J . B i e r s a c k . Dept. of N u c l e a r M e d i c i n e , U n i v e r s i t y of Bonn, Bonn, F R G

NEW RADIOPHARMACEUTICALS FOR RADIATION SYNOVECTOMY: SAFETY STUDIES IN NORMAL RABBITS AND RABBITS WITH ANTIGEN INDUCED ARTHRITIS (AIA).

I M P R O V E D S U R V I V A L OF P A T I E N T S W I T H A D V A N C E D OVARIAN CARCINOMA AFTER REPEATED IMMUNOSCINTIG R A P H Y A N D I N D U C T I O N OF A N T I - I D I O T Y P I C A N T I BODIES. A n e w a p p r o a c h of i m m u n o t h e r a p y is the i n d u c t i o n of the i d i o t y p i c n e t w o r k by vaccination with antibodies against tumora s s o c i a t e d a n t i g e n s . T h i s t r e a t m e n t can i n d u c e the p r o d u c t i o n of a n t i - i d i o t y p i c a n t i b o d i e s w h i c h are m i m i c k i n g the i n t e r n a l i m a g e of the t u m o r a s s o c i a t e d a n t i g e n and so m o d u l a t e the h o s t ' s i m m u n e r e s p o n s e . We i n v e s t i g a t e d 14 p a t i e n t s w i t h o v a r i a n c a r c i n o m a s w h o r e c e i v e d s i n g l e or s e v e r a l i n f u s i o n s of 1 3 1 - I - l a b e l e d F ( a b ) 2 a n t i b o d y f r a g m e n t s for i m m u n o s c i n t i g r a p h y d u r i n g the t i m e b e t w e e n 1985 and 1990. T h e p a t i e n t s w e r e in an a d v a n c e d stage of o v a r i a n cancer. T h e y w e r e t r e a t e d in the same m a n n e r by s u r g e r y f o l l o w e d by c h e m o t h e r a p y . F i v e of the p a t i e n t s w i t h s e v e r a l i n f u s i o n s s h o w e d r i s i n g l e v e l s of tumor m a r k e r a n t i g e n in v i t r o w i t h o u t any c l i n i c a l s i g n of r e c i d i v a t i o n . It t u r n e d out t h a t the e l e v a t e d l e v e l s w e r e c a u s e d by a n t i - i d i o t y p i c a n t i b o d i e s d e v e l o p e d in the p a t i e n t s after r e p e a t e d immunoscintigraphy. In 1990, we o b s e r v e d that o n l y these five p a t i e n t s w e r e still alive. A l t h o u g h our r e s u l t s r e f e r to a small group, we p o s t u l a t e a b e n e f i c i a l r o l e of the i n d u c t i o n of the i d i o t y p i c n e t w o r k against a tumorassociated antigen resulting in an i m p r o v e d s u r v i v a l a f t e r v a c c i n a t i o n of p a t i e n t s w i t h a n t i b o d y f r a g m e n t s .

The use of 6- emitting radionuclides for the treatment of rheumatoid "arthritis (radiation synovectomy) has significant clinical impact. A number of radiopharmaceuticals (RP) have been evaluated previously using Y90, Au-198, Dy-165 and a wide variety of carrier systems (colloids, Ca. oxalate and FHMA particles). While these RP showed some clinical efficacy, unacceptable extra-articular leakage of radioactivity (EALR) limits clinical applications. Using Hydroxyapatite (HA) as the carrier, we have developed a new class of RP with several different radionuclides such as Sm-153 (T~=l.95d, E~-=O.8MeV), Ho166 (T~=l.ld, E~-=I.84MeV) and Re-186 (T~=3.7d, EB-= 1.07Me?). Thes~ RP were prepared with high labeling efficiency and showed excellent in vitro stability in saline and plasma. The safety studies were designed to determine in rive stability and EALR. 300Bci of each RP was injected into one of the knees of normal rabbits (NR) and rabbits with AIA. Daily blood samples and total urine excreted was obtained over a period of 2-3 half-lives of the radionuclide. The animals were sacrificed and % I.D. in major organs and urine was calculated. The total EALR was less than 1% with Sm-153 and 3% with Re-186. Whereas non HA controls (Re-186-HEDP and Sm-153 citrate) showed most of the activity in the urine. These results indicate that radionuclides bound to HA particles almosttotally retained in the synovial joint and are suitable for RS.

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Monday, 2 September 1991

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G.WESTERA*, H.W. REIST**, F. BUCHEGGER***, A. PFEIFFER*, G.K. VON SCHULTHESS*, J.P. MACH***. *Department of Radiology, Clinic of Nuclear Medicine, University Hospital Z0rich, 8091 Z~irich, **Paul Scherrer Institut, Villigen, ***Institute of Biochemistry, University of Lausanne; Switzerland.

Wessely R,

RADIOIMMUNO POSITRON EMISSION TOMOGRAPHY WITH 124-1LABELED MONOCLONAL ANTIBODIES : A NEW APPROACH FOR QUANTIFYING IN VIVO TUMOR CONCENTRATION AND BIODISTRIBUTION. Radioimmunodetectien (RID) of tumors with monoclonal antibodies (MAbs) is becoming an established procedure. Positron emission tomography (PET) shows better resolution than the normal gamma camera and single photon emission tomography and can provide more precise quantitative data. Thus, in the present study, we have combined these powerful methods to radioimmuno PET (RI-PET). MAbs, directed against carcinoembryonic antigen (CEA) (an IgG, its F(ab')2 and a mouse-human chimeric IgG derived from it) were labeled with 1241-iodine, a positron emitting radionuclide with a convenient physical half life of 4 days. Mice, xenografted with two CEA producing human colon carcinomas (2 cm apart) were injected with the 1241_MAb and the tumors were visualized by PET. The concentration of 1241in tumor and normal tissue was determined both by PET and by direct radioactivity counting of the dissected animals, with very good agreement. To allow PET quantification, we established a procedure to account for the presence of radioactivity during the absorption correction measurement (transmission scan). All three variations of MAb clearly delineated the tumors (as small as 0.2 g) with good resolution. Comparison of PET and tissue counting gave e.g. for the concentration ol intact murine MAb by PET 6.8 and 6.4 %id/ml and by tissue counting 7.1 and 6.5 %id/g. This shows, that this novel combination of radio immune localization and PET (RI-PET) will provide, in addition to more precise diagnosis, more accurate radiation dosimetry for radioimmunotherapy.

*Matzku S, Bihl H:

Klinik fi~r Nuklearmedizin, Katharinenhospital Stuttgart, *Merck Darmstadt. COMPARISON OF RADIOACTIVITY AND DOSE DISTRIBUTION IN NUDE MOUSE XENOGRAFTS BY MEANS OF AUTORADIOGRAPHY (AR) AND MINI-THERMOLUMINESCENCE DOSIMETERS (TLDs) The method of mini-thermoluminescence dosimetry (originally described by BW Wessels) was established to evaluate energy dose distribution (DD) in nudemice with different types of human tumor xenografts after administration of radiolabelled monoclonal antibodies (MAbs). It was thus possible to compare radioactivity distribution (RD) to DD, the one being assessed by AR, the other by mini-TIDs implanted into nude mouse xenografts. The question can be posed to what extent non-uniformity of RD in tumor xenografts will be "levelled out" by the range of B-particles. Mice were treated with 1-131-1abelled MAbs and TLD rods were implanted in the tumor xenografts. From serial sections of tumors ARs were produced to visualize RD, while DD was determined from indwelling mini-TLDs. The tumors investigated showed qualitatively differing RDs, i.e. focal, peripheral and near-uniform distribution. DD was influenced by two components, one of them being long-to-medium ranged, the other short-ranged. The former component was common to all tumor types, while the latter was typically observed in tumors with highly non-uniform RD, leading to a marked heterogeneity in DD. This data provide yet another explanation for the limited success of radioimmunotherapy in some tumor types and emphasize the need for higher energy B emitters for the therapy of macroscopic tumor nodules.

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E. Busemann Sokole

W.J. MacIntyre, R.T. Go, M. Antar, D.R. Neumann, S.A. Cook, G.B. Saha, B. Sufka, T. Kaczur. Department of Nuclear Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, 44106 U.S.A.

Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands NC~-UNIFORMITY ~ ' ~ C T S

FROM COBALT-57 FLOOD SOURCES.

Cobalt-57 flood sources are widely used for . -scintillation camera uniEormity quality control. ',heir use with large detectors seems p~rticulariy attractive. A re _ctang~l_ar 57Co ~lood source has recently been produced, with a nominal 5vCo activity oz 370 ~ and less than 0. 1% contribution zrom each ol the impurities of 5~.o, s8C9_, and 6oCo. The Cormpton scatter zrom high energy [>500 keY) game_ emisslons from these irmpurities, as well as from 57Co itself (0. 14%)~ is known to influence images. In older generation scintillation cameras, r~ne effect was to . smoor_n unizormity, but aegraae reso-u~ion ana conr_ras~. When used with a modern rectangular camera ~ low . energy, a l l - ~ . u r ~ e collimator, the rectangular flooa source speciziea above inr_roaucea conslaeran~e nonuD/'formi%y seen as hot areas di^s^tributed over the whole zield-oz-view. A dead time oz zu~ was oEservea, althoug h the count rate was about 30k counts per sec within the 20% enerc~ window centred over the 5vCo photopea]c Increased-distance bet%~en the svCo flood source and collimator face reduced, but not eliminated, both dead time and non-uniformity. Meas urgments wlth medium and high energy collimators exhibited these effects to a lesser ~ e n t than. with the low energy collimator. 'Ine effecr_s were s~ill a P l ~ n t three months later. The results were not r~plicable wir_n a 99r~fc filled flood source, even at much higner count rates within the gg~Tc energy window. In conclusion, caution when using 5vCo flood sources has traditionally been advocated/ This a p p e a r s e v e n more relevant wi%h modern cameras since non-unlzormlty may be introduced, presumably due to high energy gamma rays.

530

VARIATION OF INTER- AND INTRA-SLICE UNIFORMITY MULTISLICE PET SYSTEM: NEED FOR QUALTIY CONTROL

IN A

Multislice PET units have the advantage of permitting greater axial sampling so that a non-symmetric organ such as the heart can be re-oriented from a body axis acquisition to allow display in cardiac short and long axes. The multislice technique, however, will usually exhibit a variation of sensitivity with alternate slices of direct and cross planes. The fidelity of the three dimensional reconstruction will be dependent on the variation of uniformity, not only between slices, but within the individual slice itself. These interand intra-slice uniformities were measured on a 21 slice PET system (Positron Corporation, Houston, Texas) by imaging an elliptical phantom (Data Spectrum Corporation) filled with a solution containing 3mCi of Ga-68. A total of 200,000,000 coincidence counts were collected. Reconstruction was performed with the filter used in cardiac studies. To remove edge and partial volume effects the inner circles of 16cm diameter were selected. The data were acquired in 1.7xl.7x5.1n~n voxels but displayed in 6.8x6.8x5.1mm voxels for greater statistical accuracy. The variation in sensitivity of the inner 19 rings in a typical measurement gave an inter-slice uniformity of 1.4%. The intra-slice uniformity of each of the four quadrants averaged 5.5% with a variation between upper and lower quadrants of 5.6%. This program has been valuable in identifying sub-optimal operation not discerned by routine maintenance and has become a weekly quality control procedure. The inherent random variation has also demonstrated the degree of contrast resolution needed for significance in clinical studies.

Monday, 2 September 1991

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A SkrettlnG~2 S A Larsson . 2 A Karkklnen 2 ' K .Ennow ..... , 3 P O Scbnell , L Johansson Y Wang S Hyodynmaa T h e Norweglan Radium Hospital,Oslo. Karollnska Hospital, S~ockholm, -Techn Research Center of Finland, Tampere. State Inst of Radiation Hygiene, Copenhagen

KE B r i t t o n , PE A s a r d , H Bergmann, E B u s e m a n n - S o k o l e , F D e c o n n i n c k , J Dumont, P J a r r i t t , P Montero Dominguez, U N o e l p p , P P r e t s c h n e r , A T o t t - P o k r o p e k , E Vauramo. S t . Bartholomew's Hospital London, and t h e Management Committee of COST B2.

A SCANDINAVIAN MULTI-CENTER QUALITY ASSURANCE PROJECT IN N U C L E A R M E D I C I N E B O N E I M A G I N G U S I N G A T R A N S M I S S I O N B O N E PHANTOM

QUALITY ASSURANCE THE PURPOSE AND

A total performance test of bone scintigraphy was performed in 76 scandinavian nuclear medicine laboratories by means of a transmission bone phantom. Exactly equal phantoms were produced and distributed to coordinators in the actual countries. The studies with the phantom simulated the posterior view imaging of the lurabal and thorax region, and simulated accumulations were present in the ribs and in the vertebrae. The rib accumulations were constructed with the aim to carry out an ROC test. Imaging and display of the images were carried out according to the procedures used in the actual laboratories. Thus, they were free to chose information density, acquisition mode (stationary, scan) and display method. A l l images were sent to the coordinators, together with a reporting scheme. There were large variations in the performance of the different laboratories. Moreover, the results indicated that the way the image is presented is of equal importance as the camera quality.

OF SCOPE

NUCLEAR MEDICINE OF COST B2.

SOFTWARE:

The quality assurance, QA, and q u a l i t y control, QC, of Nuclear Medicine, NM, software raises the problems a n d s e e k s to p r o v i d e t h e s o l u t i o n s in w h a t is a m i c r o c o s m of the problems of QA of software in Medicine. NM encompasses the integration of c l i n i c a l information, image and curve analysis, tomography, the clinical reporting station, knowledge based decision making and the interaction with Hospital Information Systems. In a l l t h i s c o m p l e x i t y of m e d i c a l management, this project provides a philosophy a n d p r a c t i c e of Q A a n d QC of N M software that is applicable to general medical software, and develops process and p r o d u c t s t a n d a r d s in t h i s f i e l d . concepts of software phantoms, clinically validated data sets from p a t i e n t s w i t h d i s e a s e s of t h e h e a r t , k i d n e y a n d b r a i n , as q u a l i t y c o n t r o l t e s t o b j e c t s , the identification of the need for a software data exchange format the Interfile approach - t h e requirements for validation and verification as t h e c o r e of knowledge based systems, the evaluation by collaborating test centres and a coordinating centre are the essence of t h e C O S T B2 p r o j e c t . The

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M. C h l a n e l l ± , A. S i g n o r e , A. T o s c a n o , G. F. T o n n a r i n i , P. P o z z i l l i , M. Negri, G. C a n t a r a n o Servizio Speciale di M e d i c i n a Nucleare and Endocrinologia (I), Clinica Medica (If), U n i v e r s i t y "La S a p i e n z a " r Rome, Italy.

S.K.Shukla 1,2, g. Ar~ir6 I, C.Ciprianil,H.Xie3,Zh.Yao 3, G.F.WangS; l)Med.Nucl.,Ospedale S.Eugenio,Roma; 2) Ist. Cromatografia,CNR, Roma,Italy; 3) Shanzhai Inst. Cell Biology, Shanghai, China

H P L C P U R I F I C A T I O N OF 123I-LABELLED I N T E R L E U K I N 2 WITH H I G H S P E C I F I C A C T I V I T Y F O R H U M A N S T U D I E S We have previously reported that radioiodinated interleukin-2, labelled with the Lactoperoxidase and Glucoseoxidase method and purified by gel filtration chromatography ( S e p h a d e x G25) b i n d s , in vivo, to l y m p h o c y t e s i n f i l t r a t i n g e n d o c r i n e p a n c r e a s in p r e d i a b e t i c m i c e . F o r t h e a p p l i c a t i o n of t h i s t e c h n i q u e in human the purification of radiolabelled interleukin-2 from unlabelled interleukin-2 and from other reagents is r e q u i r e d . 123Iinterleukin-2 was purified by reverse phase chromatography on a HPLC column using acetonitrile:0.1% trifluoroacetic acid g r a d i e n t f r o m 2 0 % : 8 0 % to 6 5 % : 3 5 % in 60 min. at a f l o w r a t e of 1 m l / m i n . R a d i o a c t i v i t y eluted in a m a j o r p e a k at 46 m i n r e t e n t i o n t i m e w h i l e unlabelled interleukin-2 (detected at a b s o r b a n c e at 280 nm) e l u t e d in a s i n g l e p e a k at 44 m i n . F r a c t i o n s (0.5 ml) w e r e a n a l y z e d for t h e i r b i n d i n g capacity to int~=rleukin-2 r e c e p t o r of IA3 c e l l s a c t i v a t e d w i t h TPA. T h e binding assay revealed that labelled interleukin-2 retains its receptor binding capacity. Our data indicate t h a t b y H P L C is p o s s i b l e to p u r i f y r a d i o l a b e l l e d interleukin-2 with high specific activity with no contaminations of u n l a b e l l e d i n t e r l e u k i n - 2 a n d l a b e l l i n g r e a g e n t s t h u s a l l o w i n g the i n j e c t i o n in h u m a n s for the in v i v o d i a g n o s i s of s i t e s of l y m p h o c y t i c i n f i l t r a t i o n .

ANTIHEPATOMA ANTIBODY FRAGMENT, HEPAMA-I, LABELINg WITH METAL RADIONUCLIDES FOR RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY OF HEPATOMA Prerequisite for early radioimmunodetection and toxicity free radioimmunotherapy is the preparation of chromatographically and electroDhoretically pure labeled antibody that is stable in vitro and remains so in vivo. Since I-iSl-hepama-i was unstable and concentrated mainly in healthy organs of the patient,we decided to label hepama-i with metal radionuelides which form more stable and pure conjugates. Due to their chemical similarity, Ga-67 and Y-N0 were chosen to label hepama-i for their application for radioimmunodetection and radioimmunotherapy of hepatoma. There have been two approaches to radiolabel antibodies with metal radionuclides using bifunctional chelates: I. binding the chelate first to the antibody followed by radiolabeling; 2. chelating first the radionuclide which is then bound to the antibody. Our studies showed that whichever mode of labeling one selects,pure and stable radiolabeled antibody as the final product is obtained only when chromatographically and electrophoretically pure chelated antibody or radionuclide is made to react respectively with chromatographically and electrophoretically pure radionuclide or antibody. From both routes of labeling we obtained labeled hepama-i which was chemically and biologically stable. Both Ga-67- or Y-90-labeled hepama-I had high affinity for human hepatoma cells in vitro and for human hepatoma xenografts in nude mice.

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Monday, 2 September 1991

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WimTh. Goedemans, Maarten Th.M. de Jong, Edward Deutsch, Kathleen M. Miller, Jim Brodack and Geert J. Ensing, Mallinckrodt Diagnostica (Holland) B.V., Petten, The Netherlands, and Mallinckrodt Medical Inc., St. Louis, MO, USA

C=_B=_Sam~s£~ and C. Solanki

DEVELOPMENT 0F AN IN-Ill LABELLED SOMATOSTATIN ANALOGUE: OCTHEOSCAN iii Somatostatin is a naturally occurring tetradeeapeptide that inhibits secretion of many hormones and neurotransmitters. Large numbers of binding sites with high affinity for somatostatin have been reported in a variety of tumors. An octapeptide analogue of somatostatin, Octreotide (SandostatinTM), might be useful in the treatment of patients with these tumors, and has been reported to suppress cancerous cell growth (LANCET 1990, 336: 909-911). In an effort to utilize the high specificity of 0ctreotide for scintigraphic imaging of somatostatin receptor-positive tumors, a DTPAOctreotide conjugate has been prepared and labelled with In-lll by researchers at the University Hospital Rotterdam (Holland) and Sandoz Research Institute (Switzerland). Development of this agent into a clinically useful radiopharmaceutical has required the solution of several formulation problems. Most importantly, the tendency of the agent to undergo radiolytic decomposition has been circumvented by the addition of anti-oxidants such as inositol and gentisic acid. Adverse efforts of trace metal contaminants such as Cd, Fe and Cu can be avoided by choosing appropriate labelling conditions and times. This work shows that the In-lll labelled DTPA-Octreotide conjugate, called OctreoScan iii, can be consistently prepared in >90% purity and remains stable for 72 hours after labelling. Thus, OctreoScan iii appears to be a radiolabelled somatostatin analogue that is suitable for clinical investigation.

Department of Nuclear Medicine, Addenbrooke's H o s p i t a l , Cambridge. STABILISATION OF TC-99m ,EXAMETAZIME USING ETHANOL AND STORAGE AT A LOW TEMPERATURE. Tc-99m exametazime is radiochemically unstable and is required to be used w i t h i n 30 minutes of p r e p a r a t i o n . We have i n v e s t i g a t e d a number of methods of enhancing s t a b i l i t y and we present our i n i t i a l r e s u l t s . Ts-99m exametazime was prepared by r e c o n s t i t u t i o n with 2.5 mls s a l i n e and 3000 MBq pertechnetate, Hourly radiochromatographic readings were taken of primary complex (lipophilic) and of free 20mcpertechnetate- Similar determinations were made at (freezer) with and without the addition of 0.5 ml ethanol. At 6 hours levels of primary complex were 42%~7 S.D. (22°C), 17%~5 (-20°C), and 69%±4 (-20°C in ethanol); pertechnetate Levels were 45%~3 (22°C), 60%±10 (-20°C), and 16%ZI (-20°C in ethanol), n=3.

In a second experiment exametazime was reconstituted with saline or a combination of saline and ethanol, and the pertechnetate then added at daily intervals. The two components were analysed as before. At 3 days levels of primary complex were 0% (22°C), 19%~5 (-20oC), and 59%±11 (-20°C in ethanol); pertechnetate levels were 100% (22°C),78%~5 (-20°C), and 37%~I0 (-20°C in ethanol~ n=4. We conclude from both studies that a combination of ethanol and storage at -20°C markedly increases levels of Tc-99m exametazime and decreases levels of pertechnetate. The radiopharmaceutical could be used for up to three da'ys after reconstitution e.g. in the radiolabelling of leucocytes.

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M. Reymen, H. Verwimp, C. Van Nerom, G. Bormans, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem., I.F.W. and Radiopharmacy, U.Z. Gasthuisberg, K.U.Leuven, Belgium

A . D u a t t i - U n i v e r s i t y of B o l o g n a , I t a l y ; R . P a s qualini, V.Comazzi, E.Bellande, M.Lecayon, D.Hoffschir, M.Comet, J.P.Mathieu, D.Fagret CIS B i o I n t e r n a t i o n a l , C E A and CNRS, France. PREPARATION AND BIODISTRIBUTION STUDIES OF TECHNETIUM-99m NITRIDO DITHIOCARBAMATES: A NEW C L A S S OF N E U T R A L , M Y O C A R D I A L I M A G I N G A G E N T S A series of T c - 9 9 m d i t h i o c a r b a m a t e radiopharmaceuticals containing the Tc-qN m u l t i p l e bond have been prepared by substitution reactions onto a preformed TcN-intermediate, w h i c h had b e e n previously obtained through a new e f f i c i e n t r o u t e b a s e d on the r e a c t i o n of pertechnetate with the S-methyl ester of d i t h i o c a r b a z i c acid, in the p r e s e n c e of reducing p h o s p h i n e s . The characterization of the complexes s h o w e d that t h e y are square p y r a m i d a l w i t h the TcmN group in an apical p o s i t i o n , and two dithiocarbamate ligands spanning the four positions on the basal plane through the sulfur a t o m s of the -C(=S)Smoiety, thus g i v i n g a zero net charge. Biodistribution studies in a n i m a l s were c a r r i e d out in rats, dogs, a d u l t pigs and monkeys. While all the c o m p l e x e s failed to image pig heart, they s h o w e d h i g h myocardial uptakes in rats, dogs and primates. This results indicate that the Tc-99m nitrido dithiocarbamate radiopharmaceuticals accumulate in m y o c a r d i u m cells, and that their u p t a k e s are s p e c i e s d e p e n d e n t .

CRITICAL EVALUATION OF STABILIZATION METHODS FOR 99mTe-d,l-HM-PAO. 99mTc-d,l-HM-PAO (I) is at present the agent of choice to assess rCBF in patients with neurological disorders. Poor in vitro stability makes this agent less reliable and less practical. The short shelf-life of the reconstituted preparation (30 rain) and the limited activity of 99mTc that may be added to the expensive kit (1.11 GBq) have restrained this radiopharmaceutical from use on a large scale. Therefore, many investigators have tried to improve the in vitro stability of I by different methods.: (a) addition of 1 mg gentisic acid to the reconstituted kit, (b) incorporation of 2.52 mg sodium pyrophosphate in the labelling kit, (e) addition of 0.4 nag NaI to the eluate before labelling and (d) dividing of the Ceretec kit in 5 fractions after reconstitution in saline, storage at low temperature and labelling when required. First, we have re-examined these methods. Analysis of I was performed by the three strip method, paper chromatography with ether and RP-HPLC. In our hands, however, none of the published methods appeared as efficient as reported. Moreover, introduction of methods a-c should not be recommended as they require manipulation of the composition of the labelling kit or the eluate. Secondly, we have tested the effect of five other weak chelating agents (WCA), two anti-oxidants (AO) or a combination of them on the stability of I. The results show clearly that not every WCA or AO enhances stability of I. The most pronounced stabilizing effect could however be realized by addition of a mixture of pyrophosphate and PABA at pH 9.5 2' after labelling. Radiochemical purity of 2.6 GBq (70 mCi)-preparations of I remained > 85 % for many hours. It is concluded that efficient stabilization of high-activity 99mTCd,I-HMPAO is possible, but a careful analysis of the radiochemical purity remains necessary before each injection.

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Monday, 2 September 1991

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U Buell, E Vosberq, R Doerr, C Altehoefer.

R.Campint, R.Giubbini, M.Gatli, O.Zoccarato, A.Vignati, P.Giannuzzi, M.Gattone, LTavazzi. Nuclear Medicine and Cardiology Dpts. Fondazione Clinica del Lavoro, Centro Medico di Veruno (NO) - Italy.

Depts Nuclear Medicine and Internal Medicine I, University of Aachen, Aachen, FR Germany

Techn

VD=vessel disease; OMI: old myocardial infarction In controls, LVPR did not systematically increase with DP. In patients, however, LVPR decreases with the severity of CAD and was significantly reduced in HY paWe conclude that the concept of perfusion tients. reserve ( P R ) provides important global parameters, inherent in the MIBI data-set and thus easily to he derived in addition to regional evaluations.

99 mTc- sesta MIBI (MIBI) SPET and simultaneous First Pass radionuclide ventriculography (FP) in the functional assessment of Anterior Infarct. The aim of our study has been the analysis of the contribution of the single and/or combined techniques to the functional assessment of the post-MI Pt. 42 male subjects affected by AMI (35_+9 days), representing a consecutive series admitted to three CCU, with no clinical evidence of cardiac failure, were studied by MIBI FP and SPET in 2 different days at rest and after exercise. The FP were evaluated for global ejection fraction (EF) and regional wall motion abnormalities (RWMA). SPET studies, with the left ventricle divided in 17 segments with the aid of a "bull's eye" display, were scored using a four levels grading. A subset of 25 Pts was studied by coronary angiography. 9 Pts (18%) developed angina during exercise, none dyspnea and 11 Pts (22%} "ischaemic" ECG-ST modifications, 8 Pts (16%) had a normal >5% increase in EF: in 7 Pts (14%) the EF failed to increase >5%. In 35 subjects (71%) a decrease was observed. Despite the absence of clinical signs 14 Pts (29%) had an exercise EF <30%. In 46/50 (92%) one or more reversible MI81 defects were documented. A significant correlation was observed between EF and total perfusion score (sum of the score of the 17 segments) after exercise but not at rest; RWMA of the antero-basal, lateral, apical segments were related to aspecific perfusion defects of the antero-septal wall, which were, on their turn, closely correlated with the site of the coronary occlusion. On the other hand, inferior uptake defects were not always related to RWMA or coronary occlusions. Thus despite the absence of angina, the majority of our Pts presented reversible perfusion abnormalities. A lower percentage showed a fall in EF or the development of new or more severe RWMA during exercise. The total peffusion score was not able to predict the functional impairment of the left ventricle in terms of global EF. Due to the planar imaging, a diskinetic segments at RNV were not precisely correlated to SPECT severe perfusion defects. Thus the two different techiniques offer original, independent and complementary information.

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G. Zuin, *M. Sicolo, *F. Dalla Pozza, B. De Piccoli, *R. Vangelista, E. Piccolo. Division of Cardiology and *Nuclear Medicine Service. Umberto I° Hospital. Mestre-Ve, Italy. Tc99m-MIBI MYOCARDIAL SCINTIGRAPHY IN PATIENTS WITH NORMAL CORONARY ANOIOGRAPHY AND HIGH PREVALENCE OF ORGANIC HEART DISEASE. The purpose of the study was to assess the specificity of Tc99m-MIBI myocardial scintigraphy (MIBI) after exercise in 17 patients (pts) (8 M, 9 F) with normal coronary angiography. All pts had history and ECG abnormalities suspected for myocardial ischemia. Nine pts were affected with hypertensive heart disease, i with mild dilated cardiomiopathy, i with valvular heart disease and 6 were free from organic heart disease. All pte underwent MIBI at rest and after graded bicycle exercise (SO W/3'). Gated planar images (ANT, LAO40 ° , LAO70 ° ) were acquired, and each endyastolic image was divided into 5 segments and scored visually (O=normoperfusion, l=mild ipopefusion, 2=moderate ipoperfusion, 3=absenee of perfusion). RESULTS: stress test: 7 pts stopped the effort after reaching the maximal predicted heart rate, 8 pts for exaustion and 2 pts for chest pain. ST depression (> I mm in precordial leads) during stress ECG was observed in 7/17 pts; 3/17 pts exhibited mild stress scintigraphic ipoperfusion of the apex (score i, specificity = 83%) and no pts showed more severe perfusion abnormalities (score 2-3). CONCLUSIONS: in our experience, in pts with normal coronary angiography and high prevalence of organic heart disease MIHI showed a very high specificity; only the apex can exhibite false positive perfusion defects.

E. K l e i n h a n s , C. A l t e h o e f e r , U. Wiegand, J. v o m Dahl, H.J. K a i s e r , U. Buell D e p t s of N u c l e a r Medicine a n d C a r d i o l o g y , T e c h n i c a l U n i v e r s i t y of A a c h e n , G e r m a n y

QUANTITATIVE MIBI-Tc-99m EXERCISE-REST SPECT FOR THE EVALUATION OF LEFT VENTRICULAR PERFUSION RESERVE (LVPR) A correlate to coronary vascular reserve may he obtained during myocardial SPECT from an exercise E/rest R ratio of global left ventricular uptake values (GLV) of Tc-99m MIBI as LVPR. In the present study 27 pts with no CAD (controls), 104 pts with CAD (of these, 70 had coronary anglo) and 19 pts with hypertensive heart disease (HY) without CAD were exercised and Tc-99m NIBI was injected twice (150 MEg E, 800 MBq R) within a 4 hrs protocol. With SPECT (double-head, 2x180 ° ), GLV uptake (kcts) was determined by summing up six slices (2 pix thickness). After correction (dose, decay, loss), LVPR was computed by division (E/R; extraction fraction not corrected). For correlation, the doubleproduct at E (DP) from RRsyst-max x heart rate-max was formed. Results were subgrouped for various findings: n (pts) LVPR (X±SD) DP (~ x E+03) Controls 27 1.73 ± 0.26 30 HY, no CAD 19 1.58 ± 0.20* *p<.025 28.5 HY and CAD 32 1.53 ± 0.26* to (.01 26.5 CAD, I-VD 54 1.52 ± 0.24* vs con- 24 OMI, posterior 27 1.49 ± 0.22* tro~s 24 OMI, anterior 30 1.44 ± 0.21' 21 CAD, 2/3-VD 17 1.39 -+ 0.18" 19.5

QUANTITATIVE TL-201 SPECT AND CORONARY ANGIOGRAPHY IN THE FOLLOW-UP AFTER SUCCESSFUL PTCA Within six m o n t h s a f t e r s u c c e s s f u l PTCA, r e s t e n o s i s o c c u r s in m o r e t h a n 30% of t h e p a t i e n t s . The aim of t h i s s t u d y w a s to r e v e a l q u a n t i t a t i v e c r i t e r i a in T ] - 2 0 I SPECT f o r d e t e c t i o n of r e s t e n o s i s . I n 38 p a t i e n t s q u a n titative T1-201 SPECT and coronary angiography ( m e a s u r e m e n t s of v e s s e l ~tiameter) w e r e p e r f o r m e d b e f o r e PTCA a n d w i t h i n a p e r i o d of six m o n t h a f t e r PTCA. Res t e n o s i s w a s d e f i n e d a n g i o g r a p h i c a l l y b y a loss of >50% of t h e initial b e n e f i t a n d / o r b y s t e n o s i s >50% of luminal d i a m e t e r . By m e a n s of SPECT d u r i n g e x e r c i s e a n d a t r e s t , in 33 m y o c a r d i a l r e g i o n s of a b o u t 5 ml size p e r f u sion a n d r e d i s t r i b u t i o n w a s d e t e r m i n e d r e l a t i v e to t h e p e r f u s i o n a l maximum. B e f o r e a n d a f t e r PTCA, i n t r a i n d i v i d u a l d i f f e r e n c e s w e r e c a l c u l a t e d r e f e r r i n g to t h e 3 r e g i o n s w i t h minimal p e r f u s i o n a n d maximal r e d i s t r i b u t i o n , R e s t e n o s i s as c o m p a r e d to s u f f i c i e n t p a t e n c y r e v e a l e d significant different results: no c h a n g e s in min. p e r f u s i o n max. r e d i s t r .

restenosls (n=25) +18.0+13.3 -14.8+17.9

restenosis (n=13) -1.8_+14.7 +9.4+31.4

R<0.001 p<0.001

B y m e a n s of R O C analysis, a threshold of 5% increase of minimal perfusion was found to be optimal in discriminating s u f f i c i e n t p a t e n c y f r o m r e s t e n o s i s . T h u s , s e n s i t i v i t y was 77%, a n d s p e c i f i c i t y 88% r e s p e c t i v e l y . We c o n c l u d e t h a t q u a n t i t a t i v e SPECT is a u s e f u l tool in t h e followu p - p e r i o d a f t e r PTCA.

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Monday, 2 S e p t e m b e r 1991

FP-2D3-5 P.Y. MARIE, N. DANCHIN, G. KARCHER, Y. JUILLIERE, S. BRIANCON, E. ALLOT, F. CHERRIER, A. BERTRAND Depts of Nuclear Medicine and Cardiology, CHU Nancy-Brabois - 54500 VANDOEUVRE France DETECTION OF QUANTITATIVE CORONARY ANGIOGRAPHY-DEFINED RESTENOSIS AFTER CORONARYANGIOPLASTY BY EXERCISETL-201 TOMOSCINT[GRAPHY WITH REST REINJECTION : A PROSPECTIVE STUDY This prospective study assessed the ability of exercise SPECT TI 201 with rest reinjection to detect restenosis, documented by quantitative coronary angiography (QCA), after coronary angioplasty (PTCA). Of a consecutive series of 93 pts with successful single (n=80) or multiple (n=13) PTCA for documented myocardial ischemia, 86 had re-angiography at 6 months or earlier in case of recurrent symptoms. Of these, 63 with no or mild symptoms had coronary angiography immediately preceded by TI-201 Ex SPECT with 1 mCi rest reinjection. Using the CAAS QCA system, restenosis (>50 % reduction of luminal diameter) was present in 19 of the 72 dilated segments (26%). Ex-SPECT showed a stress defect reversible after reinjection in the PTCA-related area in 27 pts. The sensitivity, specificity and predictive accuracy of Ex-SPECT to detect restenosis were 95%, 83% and 86% respectively (in contrast with 37%, 81%, and 69 % for exercise ECG alone). Stepwise multivariate analysis using the data from both Ex-SPECT and exercise test showed that presence of a reversible TI defect was the only significant predictor of >50% restenosis (p<0.001). Therefore, in a population of pts asymptomatic or with stable symptoms after single or multiple PTCA, Ex-SPECT with rest reinjection is, in contrast to exercise test alone, an excellent method to detect restenosis and thus to select pts for repeat coronary angiography.

FP-2G3-1 K. Scheidhauer (i), C. J a c k i s c h (2), J. Sciuk (i), W. Brandau (i), R. Gruner (3), O. Schober (i). Depts. of Nuclear M e d i c i n e (i) and G y n e c o l o g y (2), University of Muenster; A m e r s h a m Buchler Braunschweig (3); FR Germany. IN-VIVO R E C E P T O R IMAGING U S I N G 1-123 - E2 IN BREAST CANCER The estradiol (E2) receptor (ER-status) of breast cancer is important for prognosis and therapy. A non-invasive technique for specific diagnosis of primary breast cancer and metastases by E2 receptor imaging would be advantageous. We report the use of 16- -I-123-Iodoestradiol-17-B (I-123 - E2) in 16 patients with suspicion of primary breast cancer: 1 - 3 hrs after iv-injection of iii M B q carrier free 1-123 - E2, scintigrams were acquired including planar images of the thorax, whole body scans and tomographic images (SPECT). ER-status and tumor localisation were not known before image interpretation. All tumors were studied by conventional imaging techniques and surgically confirmed. 4 patients with benign disease and negative ER-status had true negative scintigrams; in 12 patients w i t h proved breast cancer (tumor size < 1 cm to 4 cm in diameter), E2-scintigraphy revealed the results (classification true/false is based on the ER-status: cut off >/= i0 fmol/mg tissue): 6 true positive, 3 true negative, 2 false negative, and 1 false positive. Use of SPECT seems to be mandatory. These results indicate, that 1-123 - E2 may p r o v i d e an in vivo imaging technique using the positive estrogen receptor status in primary and m e t a s t a t i c breast tumors and may provide information about the receptor localisation and distribution in breast cancer tissues.

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B.Briele,A.Hotze,U.Schmidt,D.Krebs,H.J.Biersack

C Schatten*, N Pateisky*, P Angelberger**, A A Epenetos***; * I.Dept.Gynecol.Obstet., University Vienna. ** Dept. Radiopharm., Austrian Research Centre *** RPMS Hammersmith Hospital, London. LYMPHOSCINTIGRAPHY WITH ~2~I-LABELLED EPIDERMAL GROWTH FACTOR IN CERVICAL CANCER. Radiolabelled monoclonal antibodies to epidermal growth factor receptors (EGFR) have been used both to localise and treat several malignant neoplasms, slow extravasation to the extravascular and intratumoural compartments with the in vivo administration of antibodies led to an alternative approach using the epidermal growth factor (EGF) itself. The aim of this study was to assess whether ~z3I-labelled EGF can concentrate in lymph node metastases of squamous cell carcinoma of cervix. 14 patients with cancer of the uterine cervix stage III and IV were selected because of their high probability of lymph node metastases. Planar scintigrams of the legs and the abdomen were recorded in anterior and posterior projection up to 24 hours following subcutaneous injection of 50 ~g EGF (185 MBq ~23I) into the web space of each foot. Scintigraphlc images were interpreted without knowledge of computerised tomographic (CT) scans (n=13) and ultrasound (us, n=9) of the pelvis. In 2 patients we performed diagnostic biopsy of pelvic lymph nodes. Nodal involvement was confirmed by CT for 4 of the II positive EGF scans, by US for 2 and by both biopsies. Despite strong clinical suspicion, the positive EGF scans could not be confirmed by CT or US in the 6 remaining patients. Our findings suggest that targeting of cervical cancer lymph node metastases can be achieved by in vivo binding of ~ 3 I - E G F onto EGFR on tumour cell surfaces.

Depts of N u c l e a r M e d i c i n e and Gynecology U n i v e r s i t y of Bonn, Bonn, FRG

I M A G I N G W I T H 1 - 1 2 3 - L A B E L E D E S T R A D I O L IN B R E A S T TUMORS OF EQUIVOCAL HISTOLOGY. A m u l t i c e n t e r trial was initiated to evaluate the significance of 16alpha[I-123]-iodoestradiol17beta (I-123-E2) in b r e a s t tumors. These data are part of the trial. P a t i e n t s / m e t h o d s : 19 pat.(age: 18-77 years) with equivocal histology. They received Iii M B q 1-123 labeled E2 i.v. Imaging modalities: a) Perfusion study of mammary region: 0-20 m i n p.i. (i frame/min), b) Planar images: 20-60 min p.i.; c) SPECT of the chest; d) Delayed planar images: 3-5 h p.i.; The scintigraphic findings were correlated with the results of surgery and receptor status according to R e m m e l e (score: 0-12). Results: Histology: 3 breast cancers (score: 0/8/9); 6 m a s t o p a t h i e s (score:3/8, 4 w i t h o u t status); 8 fibroadenomas (score:2/3/4/4, 4 w i t h o u t status); 2 lipomatous breast tissues w i t h o u t m a l i g n a n c y (score: 4/4). Scintigraphio results: Breast carcinoma true positive: 2/3; 1 ductal carcinoma (score: 0) true negative. 2 False p o s i t i v e findings: m a s t o p a t h y (n=l) and lipomatous breast tissue (n=l). All other scintigraphic findings were true negative (n=14). Conclusions: 1. Imaging w i t h 1-123-E2 may enable differentiation of r e c e p t o r - p o s i t i v e tumors from negative. It seems, however, necessary to define a borderline. 2. The m e t h o d could be of value in the followup of breast cancer w i t h known receptor status.

534

Monday,

FP-2G3-4

2 September

1991

FP-2G3-5

R.P. Baum, A. Hertel, T. Baew-Christow, T. Noujaim, G. HSr. Goethe University Medical Center, Frankfurt/Main, FRG; University of Edmonton, Canada

R.P. Baum, A. Hertel, T. Baew-Christow, D.M. Goldenberg, W. Kramer, D. Jonas, G. Hfr. Goethe University Medical Center, Frankfurt/Main, Germany; CMMI, Newark, N J, USA

A NOVEL Tc-99m LABELED MONOCLONAL ANTIBODY AGAINST CA125 (B 43.13) FOR RADIOIMMUNODETEC. TION OF OVARIAN CANCER - INITIAL RESULTS

FIRST CLINICAL RESULTS WITH A TC-99m LABELLED MONOCLONAL ANTI-AFP ANTIBODY IN GERM CELL AND LIVER TUMORS

Crucial to improve the poor prognosis of ovarian cancer, is the more effective treatment of recurrences after primarc surgery and chemotherapy. CA 125 has been proven as a sensitive tumor marker indicating disease activity. The aim of the present study was the evaluation of a new Tc99m labeled monoclonal antibody -B 43.13- (Biomira, Edmonton, Canada) that recognizes the CA 125 antigen. After obtaining informed consent, 14 patients (age 37-69) with increased CA 125 titers (range 46.5-1510, median 268 U/ml) and ovarian cancer were studied. Initial tumor stages were: FIGO I, II n---4, FIGO III n= 4, FIGO IV n = 5. One patient was evaluated for the detection of an unknown p r i m a ~ tumor after resection of a CA 125-producing metastasis. 11 ?attents were studied with Mab B 43.13 for the first time, 3 patients had received other Mabs before. 10 patients were monitored for the development of human anti-mouse antibodies (HAMA) Using a l-vial kit, 1 mg B 43.13, labeled with 520-1100 MBq Tc99m (mean labeling efficiency 96.7 %) was injected i.v and whole body imaging was performed by planar and SPECT 4-7 and 18-24 h p.i. The antibody application was tolerated well. The images were of excellent quality. Immunoscintigraphy detected a number of new tumor sites: In 12 pts lymph node metastases were found in 6 , peritoneal carcinosis in 7, local recurrences in 3 and liver metastases in 3. 2 pts did not show antibody uptake. 5/10 patients developed increased H A M A titers. Based on these first clinical results we conclude that Tc-99m labeled MAb B 43.13 yields useful clinical results which can be crucial for improving the poor prognosis of ovarian cancer.

Al?ha feto protein (AFP) is the leading tumor marker for monitoring germ cell tumors and prima.ry, liver carcinomas. Tumor recurrences are indicated by nsmg serum levels; conventional .imaging procedures, however, are often negative at early tumor stages. The aim of the present study was to evaluate a Tc-99m labeled marine monoclonal anti-AFP Fab' fragment (Immunomedics, Warren, N J) in patients (aged 6 to 48 years) with germ cell and liver tumors (n=4, respectively), with increased AFP titers indicating recurrences. 11 studies in 8 patients (pt) were performed (1 pt studied twice, 1 pt studied 3 times). Serum AFP prior to imaging ranged from 68-20,000 ng/ml (median: 385). Conventional diagnostic workup was negative or inconclusive in all patients prior to immunoscintigraphy. 1 mg of the antibody was injected iv after labelling with 450-1100 MBq Tc-99m (1-vial labelling kit, mean labeling efficiency 98 %). Application was tolerated well with no side effects. Imaging was performed planar and by SPECT 2-6h and 20-24h p.i. The images were of high quality. In one child with hepatocellular carcinoma recurrence (serum AFP 68), no specific tumor uptake was seen. In 4 pts, 6 new tumor sites were detected by AFP-radioimmunodetection and later on confirmed surgically. Mesenteric lymph node metastases were clearly visualized 10 months prior to CAT scan diagnosis and subsequent surgical confirmation. Based upon these initial results, we conclude that this antiAFP antibody yields useful clinical results, especially in patients with occult, recurrent AFP-producing tumors.

FP-2G3-6

A. DimitrakoDoulou. LG. Strauss, U. Haberkorn, R Hohenberger, G. Wolber, F. Oberdorfer, G. van Kaick. German Cancer Research Center, Heidelberg, FRG. ESTIMATION OF FLUOROURACIL (FU) THERAPY RESULT, BASED ON PET MEASUREMENTSOF FU UPTAKEIN LIVERMETASTASES. Response to Fluorouracil (FU) chemotherapy in p a t i e n ~ with metastatic colorectal carcinomas necessitates the accumulation of the cytostatic agent in the lesions, t h e r e f o r e measurements o f the FU metabolite concentrations are required prior to chemotherapy in order t o estimate therapy outcome. Positron emission t o m o g r a p h y (PET) With F-18 labeled FU can be used to quantify the FU metabolism in metastases, w e used PET t o evaluate the FU metabolite concentrations in 18 metastases (11 patients) prlor to FU chemotherapy. CT preceeded each PET study in order t o determine the target area f o r PET and t o calculate the t u m o r volume f r o m the CT cross sections. All patients received FU chemotherapy (500-1500 rag/m2/24 h) after t h e PET study, F o l l o w - u p CT examinations were performed f o r 3 - 9 m o n t h a f t e r onset o f chemotherapy and the t u m o r volume was measured f r o m the El" images. The t u m o r g r o w t h rate was CalCulated f r o m the volumetric data and compared t o the PET measurements o f the FU metaboIlte concentrations prior to the first chemotherapy. A linear correlation (r)0.8) was obtained f o r the standardized FU metabolite concentrations (SUV) in the metastases and the g r o w t h rate. Cluster analysis demonstrated three groups: SUV <2.0 was correlated with increasing t u m o r volume; SUV 2.0-3.5 was associated with stable disease; SUV >3.5 was observed In lesions w i t h decreasing volume. Our data demonstrate, t h a t PET can be used to estimate t u m o r g r o w t h prior t o FU chemotherapy. Therefore, i m p o r t a n t information can be obtained f o r therapy planning using PET scanning with F-18 labeled fluorouradl. Furthermore, d i f f e r e n t therapeutic protocols (e.g. regional application, p r e t r e a t m e n t w i t h folinic acid) can be compared on the base o f PET measurements PET should find preferential use for FU chemotherapy planning.

FP-2H3-1 F. H6flin, D. L~ischer, B, Jakob Dept. of Nucl. Medicine, University of Berne, Switzerland. ESTIMATION OF EFFECTIVE RENAL PLASMA FLOW: COMPARISON OF A NEW TWO-COMPARTEMENT, TWO-SAMPLE, PC BASED TECHNIQUE VERSUS OBERHAUSEN- AND TAUXE METHOD. In Continental Europe the Oberhausen method, a two plasma sample method can be regarded as state of the art in routine Nuclear Medicine ERPF measurement and is well introduced. Especially in North America ERPF is estimated by either the tedious multiple sample method according to Sapirstein or relying on the much simpler one plasma sample technique according to Tauxe. in 1989 a Two Sample, Two Compartement computer programm to estimate ERPF written in the computer language C and running on a

PC was published by Lear et al. We present here a comparison of L,~ th~'ee methods, summarized here as" Oberhausen/Tauxe/Lear. in 63 patients (ERPF/Oberhausen range 20-750 ml/min) the results according to Oberhausen calculated on a PDP-t t computer (Gamma11 software) were compared with the results according to Lear calculated on a Macintosh II Fx (NucLear software). In 2.~ of these patients the correlation Ober~ausen/Tauxe and Le~ '~auxe was established. Oberheusen versus Levi gives a correlation coefficier,~ of: r = 0.95, y = 1.0ix +-0.04. Oberhausen versus Tauxe: r = 0.86, y = 1.31x +-0.31.

Lear versus Tauxe: r = 0.89, y = 1,50x +-0.30. As expected from a theoretical point of view Oberhausen versus Lear match very well over the whole range of ERPF, but the correlation Tauxe/Oberhausen and Tauxe/Lear is distinctly poorer. Conclusions: 1.) The time honoured Oberhausen method which can be calculated without major computing power and works as well with a Gamma Camera as with probes is still excellent. 2.) The new Lear method, which is at least as simple for the patient and personel as the Tauxe method should be used if the prerequisites for the original Oberhausen method cannot be met.

535

Monday,

2 September

1991

FP-2H3-2 H Kynaston, M 0'Driscoll, J Yates, B Taylor,

S Jenkins, K Parsons. Departments of Nuclear Medicine and Surgery, Royal Liverpool Hospital, Liverpool, U.K. FRACTIONATION OF CARDIAC OUTPUT TO DETERMINE ORGAN BLOOD FLOW USING PERTECHNETATE AND MAG 3. Non-invasive determination of f'enal blood flow using a reeirculating gamma emitting tracer is based on the principle of fractionation of cardiac output (Peters et al 1987). We have used this technique to determine renal blood flow in an experimental model (Wistar rat). Renal blood flow was determined using both intraventricular and intravenous injections of perteohnetate and Mag 3 and expressed as a percentage of cardiac output. The results obtained were compared with blood flows determined by intraventricular injection of radiolabelled mierospheres. There was a significant correlation between the methods for calculating renal blood flow when either intravenous or intraventricular pertechnetate was used (r=0.88 p 0.01; r:0.87 p O.OOl). There was also a significant correlation between measurements w h e n M a g 3 was used either by intravenous or intraventrieular injection (r=0.93 p 0.001; r=0.8S p 0.01). These results confirm that pertechnetate and Mag 3 may be used to determine renal blood flow and is expressed a percentage of cardiac output. Ref: AM Peters, RD Gunasekera, BL Henderson, J Brown, JP Lavender, MDe Souza, JM Ash and DL Gilday. Noninvasive measurement of blood flow and extraction fraction. Nuc Med Comm 1987;8 823-837

FP-2H3-3 M. Tondeur *, J.P. Binon o, p. Decostre ~, E. Delcourt o, p. Hermans z~, P. Merlo ~, M. Rubinstein °, Y. Salmon o p. Wanet ° and A. Piepsz*. Hospitals Saint-Pierre *, V@sale o, Jumet o, Jolimont z,, Ixelles" BELGIUM HOW ACCURATE IS MAG3 GAMMA CAMERA CLEARANCE DETERMINATION ? This multicenter study, performed in 15 patients, was designed to compare MAG3 gamma camera clearance (C CI) determinations with plasma clearance (PI CI), calculated by a biexponential fit using 8 blood samples obtained between 1_0and 120 min. C Clwas determinedas the ratio between the slope of the background corrected renal curves and the plasmatic curve, obtained from a precordial curve calibrated by means of a plasma sample. Correctionfor kidney depth was performed using two lateral frames obtained at the end of the 20 min recording period. Using the 10 or the 20 min plasma sample for precordial curve calibration, C CI correlated well (r=0.90 and 0.95) with PI CI but there was an important overestimation: C CI = 1.5 PI C1-10for 10 min calibration, and 1.6 PI C1-16 for 20 min calibration. The use of 3 different ROIsfor background subtraction didn't change these results and is thus not responsible for the error. Despite the high protein binding of MAG3, the overestimation could be due to the precordial curve, which includes both intra and extravascular compartments and is therefore not a good representation of the plasma curve. Considering the pulmonary area as representativeof the extravascular compartment, we performed a correction of the precordial curve by means of the pulmonary curve. This procedure reduced the overestimation: C CI = 1.3 PI CI - 17, but correlation deteriorated (r=0.87), with a SEE=43 ml/ min, probably because of pulmonary counting fluctuations; moreover the pulmonary ROI was impossibleto delineate in 4 patients. Analysis of the data also suggest that kidney depth is overestimated when using MAG3. These results suggest that the external detection of plasmatic activity is responsible, at least partly, for an important overestimation of gamma camera MAG3 clearance; depth correction, using lateral frames, could also play a role in this systematic error.

FP-2H3-4

FP-2H3-5

J. Kotzerke, C. Unger, H. Hundeshagen Abteilung Nuklearmedizin und spezielle Biophysik, Medizinische Hochschule Hannover (Germany)

T.INABA, H.TAKADA, K.WAKITA, M.YAMASHITA, H.NAKAHASHI AND H.WATANABE. NISHIJIN HOSPITAL AND KYOTO PREFECTURAL UNIVE~SIT~f OF MEDICINE, KYOTO, JAPAN, 602.

SIMULTANEOUS CLEARA~qCE ~=A~UHE:ME:N I ~/ITR WHOLE-BODY COUNTER AND GAMMA CAMERA USING 99MTC-MAG3 AND THE OBERHAUSEN TECHNIQUE While the feasibility of 99mTc-MAG3 (MAG3) as tracer for

BLOOD FLOW M E A S ~ IN THE PROSTATIC CANCER TISSUE BY POSITRON 194ISSION TOMOGRAPHY (PET) Prostatic blood flow is rarely measured partly because there is no satisfactory method for doing so. However, clinically, prostatic blood flow is very interesting as it is supposed to vary with prostatic diseases such as cancer and benign prostatic hypertrophy (BPH). Prostatic blood flow was measured with oxygen-15 water by PET. A one compartment model was applied to the prostate. A dynamic study method was applied to 5 normal subjects ( ethical approval was obtained by the ethical ccmmittee in Nishijin hospital), 6 patients with BPH and 14 patients with stage T3-4 prostatic adenocarcinoma. Prostatic blood flow was 11.6+5.0 (mean_+SD) ml/min/100g, 17.7_+5.2 (mean_+SD) ml/min/100g and 33.8_+18.6 (mean+SD) ml/min/100g for normal subjects, BPH end prostatic cancer, respectively. Blood flow in the prostatic cancer tissue was remarkably higher than that in the normal tissue (p<0.05) and also higher than that in the BPH tissue (p<0.10). On the other hand, there was no significant relationship between blood flow and pathological grading in the prostatic cancer group. Nakamura et al. measured blood flow in the prostate by a hydrogen clearance method in cases of BPH and prostatic cancer. Our data in BPH cases coincided well with theirs. However, our data in cancer cases provided a result two or three times theirs. Although the cause of this discrepancy is unknown, an elevated blood flow in prostatic cancer cases can be accepted frfxa our work on color Doppler sonography for the prostate, demonstrating a remarkable enhancement of blood flow images in such cases.

clearance measurement is under discussion, an agreement about the best clearance-technique and its standardization has not been reached yet. With the established tracer hippurane the influence of instrumentation (partially shielded whole-body counter (WBC) and a gamma camera (GC)) on whole body renal clearance derived by Oberhausen's technique (OH) was excluded (Kotzerke 1990). This study investigated the influence of the clearancetechnique in the use of MAG3 and compared the ERPF values derived by WBC and GC with that from multiple plasma

samples and two compartment analysis (2CM). ?0 pts. received 20 MBq 99mTc-MAG3 intravenously and blood samples were drawn at 3, 6, 10, 15, 20, 25, 35, 45, and 60 minutes. GC and WBC studies were done as usual. The results obtained using two different instrumentations correlated best with mean values of the 15th and 25th minute (r=0.99) over a total range from 70 to 530 ml/min. The difference between ERPF values derived by 2CM and OH was statistically not significant (p>0.05). Correlation was r=0.93 and the regression line was equivalent the line of identity. Therefore, in evaluation of kidney function with MAG3 and the gamma camera ERPF measurements can be done with the Oberhausen-technique (with GC or WBC) and blood samples at 15 and 25 minutes with negligible error compared to a 9 blood sample 2CM method. In this respect, MAG3 is not different from hippurane. Kotzerke J e t al. (1990): NucI-Med 29:101-108.

536

Monday, 2 September 1991

FP-2H3-6 M. Verhei.i, Hoefnagel.

FP-213-1 L.G.H.

Dewit,

R.A.

Vald4s

Olmos,

C.A.

T h e N e t h e r l a n d s C a n c e r I n s t i t u t e , A m s t e r d a m , NL. CAPTOPRIL T c - 9 9 m - D T P A RENOGRAPHY IN PATIENTS WITH RADIATION-INDUCED RENOVASCULAR HYPERTENSION. T h e r e n a l f u n c t i o n of 5 p a t i e n t s w i t h n o n - H o d g k i n l y m p h o m a of t h e s t o m a c h a n d 6 p a t i e n t s w i t h H o d g k i n ' s d i s e a s e h a s b e e n followed p r o s p e c t i v e ] y b y s e r i a l T c 99m-DTPA r e n o g r a p h y a n d Tc-99m-DMSA s c i n t i g r a p h y a f t e r i r r a d i a t i o n t r e a t m e n t . With a follow u p of 4-7 y e a r s , all p a t i e n t s d e m o n s t r a t e d a b n o r m a l b a s e l i n e renography (range L/R function ratio: 0.1-0.8), indicating severe unilateral radiation nephropathy. Five p a t i e n t s s h o w e d e v i d e n c e of p e r s i s t e n t l y i n c r e a s e d blood pressure. I n o r d e r to d o c u m e n t r a d i a t i o n - i n d u c e d r e n o v a s e u l a r h y p e r t e n s i o n , T c - 9 9 m - D T P A r e n o g r a p h y wag p e r f o r m e d a n d p e r i p h e r a l p l a s m a r e n i n a c t i v i t y (PRA) w a s a n a l y s e d b e f o r e a n d a f t e r c a p t o p r i l . I n 4 of t h e 5 h y p e r t e n s i v e patients captopril Tc-99m-DTPA r e n o g r a p h y showed a d e l a y in p e a k r e n a l a c t i v i t y (Tmax., c a l c u l a t e d w i t h e x c l u s i o n of p e l v i c a c t i v i t y , v a r i e d f r o m 10 to 19 rain. c o m p a r e d to 1.5 to 4.5 rain. in t h e p r e - c a p t o p r i l r e n o g r a p h y ) . T h i s w a s o b s e r v e d in h i g h d o s e i r r a d i a t e d k i d n e y s (40 G y / 5 . 5 w e e k s ) , a n d in low d o s e i r r a d i a t e d k i d n e y s {12-13 G y / 3 w e e k s ) . C a p t o p r i l did not, h o w e v e r , i n d u c e a n e l e v a t e d PRA a b o v e n o r m a l v a l u e s in a n y p a t i e n t . I n t h e 6 n o r m o t e n s i v e p a t i e n t s no s i g n i f i c a n t changes were observed. T h e s e d a t a s h o w a h i g h i n c i d e n c e of e a p t o p r i l - i n d u c e d renographic changes in patients with radiationa s s o c i a t e d r e n o v a s c u l a r h y p e r t e n s i o n . I t is a s s u m e d t h a t t h e s e c h a n g e s a r e r e l a t e d to r a d i a t i o n d a m a g e o c c u r r i n g p r e d o m i n a n t l y in t h e s m a l l e r r e n a l blood v e s s e l s , b u t f u r t h e r a n g i o g r a p h i e e v a l u a t i o n is r e q u i r e d in o r d e r to rule out severe arterial stenosis.

E. Deutsch, M. Marmion M. Kwiatkowski, D. Nosco, S. Woulte, W. Neumann, G. Grummon, J. MacDonald, L.S. Chang, K. Deutsch, F. Colombo, C. Rossetti, F. Fazio, E. et a]. Mallinckrodt Medical, Inc., St. Louis, MO, ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy, BCRC, University of Cincinnati, Cincinnati, OH. SYNTHESIS AND BIODISTRIBUTION OF A NEW CLASS OF 99m-Tc MYOCARDIAL PERFUSION AGENTS WiTH OPTIMIZED IMAGING PROPERTIES. Nonreducible 99mTc(lll) cations of the general formula trans-[99mTc(L4)(P)2] +, where P is a monodentate tertiary phosphine and L4 is a tetradentate-N202, -N2OS, -N2S2 or -$4 dianionic ligand, have been investigated. The preparation of these complexes involves initial formation of the Tc(V) intermediate [99mTc(O)(L4)]+ from 9 9 m T c V l I 0 4 ", followed by phosphine reduction/insertion to generate the nonreducible Tc(lll) core. The success of the synthesis depends primarily on the nature of the L4 donor atoms, and secondarily on the structure of the L4 Iigand. For certain tetradentate-N2OS and -N2S2 Schiff base ligands, the Tc(lll) product is produced in >97% yield in a one-step reaction, directly from a mixture of Tc(VlI), L4 and P. Selected Tc(lll) cations derived from Schiff base L4 ligands have been characterized by FAB-MS (using "carrier" 99gTc), and over eight such cations have been investigated as potential myocardial perfusion imaging agents in guinea pigs and human volunteers. As expected, the biodistribufions of the 99mTc(lll) cations depend on the pendant groups attached to the P and L4 ligands. More surprisingIy, the biodistribufions are also strongly dependent on the structure of the L4 ligand. Particularly advantageous biodistribution properties are achieved when the L4 ligand is the Schiff base dianion 1,2bis[dihydro-2,2,5,5-tetramethyl-3(2H)-furanon ato-4methyleneamino]-ethane,SWL. In human volunteers the protolypical trans-[99mTc(SWL)(P)2] + agent (Q12, with P = tris(3methoxy-l-propyl)phosphine) exhibits rapid blood clearance, high myocardial uptake, exceptionally rapid hepatobiliary clearance, and extensive renal clearance. It appears as though nonreducible 99mTc(lll) cations such as Q12 will provide a new class of myocardial perfusion agents with exceptionally useful imaging properties.

FP-213-2

FP-213-3

G. Johnson III, R.D. Okada, D.K. Glover and C. B. Hebert. Saint Francis Hospital Medical Research Institute of the University of Oklahoma Health Sciences Center, Tulsa, Oklahoma, USA.

N. P.L.G. Verhoeff, E . A van Reyen, J. Overw~g__NL uimgurg..ue~ents of Nuclear Medicine ~ Neurology, Academic Medical centre, Amsterdam, The Ne~nerlands.

A COMBINATION OF HYPOXIA AND LOW FLOW REDUCE MYOCARDIAL CARDIOTEC CLEARANCE IN ISCHEMIC MYOCARDIUM CardioTec is one of two new Technetium-labeled myocardial imaging agents which is approved for clinical use in the United States. The purposes of this study were: I) to examine myocardial Technetium-99m-Teboroxime (CardioTec) kinetics in normal and ischemic myocardium and (2) to determine the relative contributions of reduced flow versus hypoxia to the altered clearance kinetics. Methods: Isolated, perfused rat hearts (n=72) were loaded with CardioTec for one hour and clearance was monitored for two hours thereafter using a Nal detector. In 28 control hearts (Group I), flow was 12 ml/min and oxygenation was normal. In 20 hearts (Group 2), flow was 12 ml/min but oxygenation was reduced (<5% 02). In 24 hearts (Group 3), flow was 3 ml/min and oxygenation was normal. Results: Fractional Clearances for one hour were: Group

Mean ± SEM

Group i: Control .63 Group 2: Hypoxic .46 Group 3: Low Flow .32 [e = p < 0.05 from

Significance

± .01 ± .02 * ± .01 * control (Group I)]

28 20

24

Conclusions: CardioTec clearance is reduced in ischemic myocardium. This is partially due to the metabolic effect of tissue hypoxia. However, there is an additional contributing factor due to the reduced flow, per se.

OF THE BINDING OF 1-123 IOMAZENIL TO CENTRAL BENZODIAZEPINE RECEPTORS IN HEALTHY VOLUNTEERS

A K I N E T I C ANALYSIS

~eD~min 'mac whole brain images of 1-123 Iomazenil have oe in 3 healthy f,ale volunteers /age 37-50 yeays ) to determine the kinetics of braln uptake and washout. At 0-10 minL 115-140 min, 205-210 min and 2400-245 min after ingection (p. i. ) of 185 MBq 1-123 Iomazenil (spec. act. 26,307 MBq/mg), series of posterior dyhamic brain images were made (30 sec/ima~e). At 120 mln*p, i., 1 mg cold flumazenil was in~ectea,, resul~ing in a zractiofial occupancy of the rauloactlve 119and < 1%. Regions of interest were urawn around tne entlre brain and total counts were determine~. The p rcgram Kinetic of G. ~. McPhenson was used to aetermlne r_ne association rate constant (KI) ana.c~ssoclation rate constant (K-l),..and thereby the equ111mrlum c~ssocla~ion 9or~.~an~ [K~) of 1-123 Iomazeml. An aspeclflc bznding of 20 % was assume~ Results (X -+ SEM): Kobs (rain-l) K1 (E8*M-l*min-l) K-I (E-2*min-l)

0. 82 -+ 0. 24 2. 03 -+ 0. 44 2. 44 -+ 0. 09

Kd

0. 15 -+ 0. 05

(nM)

Th e Kd observed is lower than expected (Kd Flumazenil = 1 nM). It may be that either the lipophilicity of 1123 Iomazenil artificially i c ~ r s t h e - ~ in this e xperlment or that the afTinity of 1-123 Iomazenil for ~encenr-ral nenzocuazepine receptors is really greater r.na~ OZ F±umazen/±. On the basis of this experl'ment one would expect th.e tl'me after which an e ~ i ± i m r l u m has been reached an vltro of the binding o .I-123 Iom~. enll to central benzodiazepine receptors ~o De about IDU mirL Th/s study has several drawbacks: (I) only a very ow amgunt o~ receptors is actually occupied by the aDele~.±lsanq, ' maElnq estimations inaccurate; (2) aspeca~ic olnding (ac~ually aspecific binding + free ±iga~1) r~.y.vary, curing tl.me; ~3) the time needed to reacn equl±iDrzum after in3ectlng the cold Flumazenil ~s dependent on the Kd of both FIumazenil and omazenil; (4) no full displacement was achieve~ Nevertheless the study demonstrates .that planar images can De use~ zor kine~ic receptor binding analysis.

537

Monday, 2 September 1991 - Tuesday, 3 September 1991

FP-213-4

FP-213-5

F. F. Knapp, Jr., E. C. Lisic, S. Mirzadeh, A. P. Caltahan, and D. E. Rice, Nuclear Medicine Group, Oak Ridge National Laboratory, Oak Ridge, TN, USA.

H. Wolf, F. Marschall, B. Woesle, E. Henze Department of Nuclear Medicine, University of Ulm, Germany ATRIAL NATRIURETIC PEPTIDES ANALOGS-

A NEW CLINICAL PROTOTYPE W-188/Re-188 GENERATOR TO PROVIDE HIGH LEVELS OF CARRIER-FREE RHENIUM-188 FOR RADIOIMMUNOTHERAPY (RAIT). Rhenium-188 (Re-188) (tt/2 = 17 h) is attractive for the radiolabeling of a new generation of monoclonal antibodies (MoAbs) for RAIT since it is available from the long-lived tungsten-188 parent (W-188, tt#2 = 69 d), has an energetic g- (Ear = 764 keV) and emits a gamma photon suitable for imaging (155 keV, 15%). Our first alumina-based clinical prototype W-188/Re-188 (75-85% Re-188) tandem generator system using HFIR-produced W-188 (2.6-5 mCi/mg) consists of: 1) an alumina column loaded with W-188 eluted with 0.9% NaCI, with subsequent elution through 2) an alumina SepPak® and 3) an ion exchange column, to provide high concentrations of carrier-free Re-188 perrhenic acid. The SepPak® is used to remove and detect any parent breakthrough. Perrhenate chemistry is similar to pertechnetate chemistry and a variety of direct and indirect labeling methods are available for radiolabeIing MoAbs. One important aspect for labeling is the Re-188 concentration (mCi/mL). Elution of our clinical prototype (e.g., 6 gm AIzO3, e.g., 85-174 mCi) with NaCI provides solutions of Na perrhenate too dilute (e.g., 2-4 mCi/mL) for high-specific-activity radiolabeling. Subsequent elution of the Re-188 bolus directly through an ion exchange column, however, provides a perrhenic acid solution which can be readily concentrated for the small volumes usually required for MoAbs labeling. The availability of this tandem system is especially important for the preparation of clinical size (>100 mCi) generators using low-specific-activity tungsten-188 which is produced in reactors with lower neutron flux. Research supported by the OHER, U.S. DOE under contract DE-AC05-84OR21400 with Martin Marietta Energy Systems, Inc.

M . F . M ~ r 2 a u _. , ] . ~ . M a d e i r a . a n t , ] M che**o.t , P. L a b a r r e , A.Veyre , J.Pa~p.o.n , M . B a y ] e ,.~.Y.. B a i r e , ** G.Despianche.s** , G. M e y n i e l - INSERM U 71, Centre Jean Facult@ de M@decine, Clermont-Ferrand **** Perrin, CIIS B i o i n d u s t r i e % G i f / Y v e t t e , France. NEW 25I-RADIOPHARMACEUTICALS FOR DIAGNOSIS AND TREATMENT FOR MALIGNANT MELANOMA (MM) An important objective of our Jaboratory is t h e design and d e v e ] o p m e n t of m e l a n o m a s p e c i f i c r a d i o p h a r m a ceuticals f o r both d i a g n o s i s and t h e r a p y , As c o n c e r n t h e diagnosis, a previous experimental s t u d y led us to s e ] e c t N - ( 2 - d i e t h y l a m i n o et h y]) 4-iodobenzamide (BZA) which is2 now u n d e r Phase II c l i n i c a l trial after labe]ing with 5 I. S c i n t i g r a p h i e s obtained between 12 and 24 hr post injection s h o w e d t h e high i n t e r e s t of this new c o m p o u n d f o r M M and m e t a s t a s e s v i s u a l i z a t i o n . ]n o r d e r to i m p r o v e dosimetry and for economica] considerations, it would be d e s i r a b l e to h a v e an a g e n t which cou]d provide the same scintigraphic informations at e a r l i e r times. ]n this a i m we h a v e d e v e ] o p e d a s e r i e s o f B Z A d e r i v a t i v e s ( F i g . ) , w h i c h 1 have been p r e p a r e d by c l a s s i c a l m e t h o d and l a b e l e d 25 with I using a s i m p l e e x c h a n g e p r o c e d u r e .

1--

@ - Y - ( C H2)n-N(R 1,R2)

: y = CONH,

RI=R2=CH3 n=2,

RI=H,

n = 2,

RI=R2=CH 5 ; 2

; --3 : Y = C O N H , R2=C2H 5

;

: Y = CONH,

n=5, R I = R z = C z H 5 _5

: Y=CONH,

n=3,

; 4 : Y=CONH,

n=2,

N ( R 1 , R 2)

=

P y r r o l i d i n e ; 6 : Y = N H C O , n=2, R = R 2 = C H 5 B i o d i s p o s i t i o n - - h a s been p e r f o r m e ( ] in B I ~ m e l a n o m a - b e a r i n g C57BL6 mice (auto[adiography~ measurement of r a d i o a c t i vity of s e l e c t e d tissues and t u m o r ) . Statistical analysis ( A N O V A ) of the r e s u l t s a l l o w e d us to s e l e c t t w o d e r i v a t i v e s according to t h e i r c l e a r a n c e : 1) F r o m 3 to 12 hr p.i., compound 2 had the highest Tumor/Blood and Tumor/ O r g a n r a t i o s , > B Z A , and a p p e a r e d as a good a g e n t f o r earlier" d i a g n o s i s i m a g i n g . 2) C o m p o u n d -4~ w i t h high r a t i o s (Tumor/Blood, Tumor/Organ) u n t i l 72 hr, c o u l d be of i n t e r e s t in31 the I.

538

field

tab.l: (liver)

t_ime(min) i0 40

ANF 1-28 4.4 3.9

ANF 5-28 3.9 3.3

70

3.8

3.0

i00

3.8

2.8

Urodilatin 6.6 4.9 4.7 4.5

An increasing tracer uptake in the head region was observed by two of the three tested iodine tracers: tab.2: (head)

time(min) 10 40 70 I00

ANF 1-28 13.6 14.9 15.6 15.9

ANF 5-28 ii. 2 12.5 12.8 13.0

Urodilatin 9.6 8.8 8.5 8.3

In conclusion the iodinated ANF 1-28 and ANF 5-28 might be potent tracers for brain imaging. It has to be verified by experiments with larger mammals.

Tuesday, 3 September 1991 FP-3DI-1

FP-213-6

[-

AN IN VlVO KINETIC STUDY IN RABBITS

The aim of this study was to synthesize and to test 1-123 labelled ANP and its analogs in order to obtain specific tracer kinetics in organs with ANP-receptors (e.g. brain, kidney, liver). Atrial natriuretic peptide (ANF 1-28), Atrlopeptin III (ANF 5-28) and Urodilatin (Thr-Ala-Pro-Arg-hANF) were radioiodinated by the Iodogen method. Radiochemlcal purity was in all eases higher than 98 %. After intravenous application of 15 MBq/kg to the rabbit the kinetic profile was investigated by whole body scintigraphy with a gamma camera. Except in liver and head no remarkable accumulations were observed. The iodinated peptides were excreted via the kidneys. The following 2 tables show the radioactivity in per cent in liver (tab.l) and in head (tab.2), relating to the whole body activity. The time activity curve of the liver decreased strongly during the first 40 minutes. Until the end of the study ANF 1-28 reached a constant value.

of

metabolic

therapy,

after

labe]ing

with

O. Schober, M. H a s f e l d * , P. Matheja, M. S c h & f e r s and G. B r e i t h a r d t * . D e p t s of N u c l e a r M e d i c i n e a n d C a r d i o l o g y * , U n i v e r s i t y of M~nster, G e r m a n y T H A L L I U M R E I N J E C T I O N VS R E D I S T R I B U T I O N IN S E V E R E S T E N O S I S OF C O R O N A R Y A R T E R I E S D E P E N D E N T ON THE C O L L A T E R A L I Z A T I O N . I m p r o v e d d e t e c t i o n of i s c h a e m i c but v i a b l e m y o c a r d i u m in h i g h - r i s k p a t i e n t s w i t h c o r o n a r y a r t e r y disease, u s i n g a s e c o n d T I - 2 0 1 i n j e c t i o n (fill-in) is reported. It w a s t h e a i m of the s t u d y to e v a l u a t e the c o r r e s p o n d i n g d e g r e e of the s t e n o s i s (> 70%) and the e f f e c t of collateralization. 57 p a t i e n t s w i t h k n o w n s i n g l e v e s s e l d i s e a s e (angiography) u n d e r w e n t stress, r e d i s t r i b u t i o n (4-hour) and r e i n j e c t i o n (24-hour) t h a l l i u m i m a g i n g (SPECT). T h r e e o b s e r v e r s i n d e p e n d e n t l y g r a d e d the s c a n s and a n g i o g r a m s . Tl-uptake/stenosis fill-in no f i l l - i n

(%)

70-90 2 6

Tl-uptake/collateral. fill-in no f i l l - i n d e c r e a s e d u p t a k e (paradox) no d e f e c t

90-99 4 Ii C+ 19 3 1 1

>99 15 3

E 21 20

C2 17 2 12

Z 21 20 3 13

In c o n c l u s i o n : I. R e i n j e c t i o n T I - 2 0 1 s t u d i e s are r e c o m m e n d e d in c o r o n a r y a r t e r y s t e n o s i s > 90%. 2. T h e f i l l i n g - i n of p e r s i s t e n t d e f e c t s (4 h) is a m e a s u r e of the h i b e r n a t i n g m y o c a r d i u m . 3. F i l l i n g - i n is s t r o n g l y a s s o c i a t e d w i t h t h e c o l l a t e r a l i z a t i o n of the stenoses.

Tuesday, 3 S e p t e m b e r 1991

FP-3D1-2 H. Valette, P. Merlet, M.H. Bourquiqnon, A. Syrota. SHFJ-CEA, Orsay, France.

UTILITY OF TI-201 REINJECTION IN PATIENTS WITH A LARGE MYOCARDIAL INFARCTION AND A SINGLE VESSEL DISEASE. TI redistribution in an infarcted area is frequently absent or too low to evidence the myocardial viability. Thus, TI Reinjection (Ri) has been proposed to overcome the absence of delayed "fill in". Therefore, the value of TI-Ri has been studied retrospectively in 184 patients observed one month after myocardial infarction: 98 without TI-Ri, 86 with TI-Ri (l.5mCi). Patients were selected for having matched age, sex, drugs, exercise level and ST depression. From short axis tomographic slices obtained after exercise and 3 hours later, bull's eye images were constructed. TI uptake (TI-U) was quantified in 9 sectors in % of the maximum uptake value. The changes in TI-U from exercise (Ex) to rest (R) were calculated in % of the initial uptake. Sectors were classified into necrotic, normal (remote from myocardial infarction) and borderline areas. Results: Patients: without TI-Ri with TI-Ri Ex-TI-U normal: 91+8 89.3+8 Ex-TI-U border area: 74_+12 74.5_+7 Ex-TI-U necrotic area : 67+14 64.4+11 R-TI-U border area: 6.9+7.5 9.2+6.5 R-TI,U necrotic area: 6+5.3 5.2+5 In the two groups of patients, the corresponding values of the Ex-U-TI were not different in the 3 kinds of areas (ANOVA). R-TI-U in the borderline and necrotic areas were not significantly increased by TI-Ri. Thus, TI-Ri does not appear to be contributive for the decision of invasive interventions which are contemplated for myocardial salvage in Patients with a large myocardial infarction.

FP-3D1-4 L Bontemps, X Geronicola-Trapali, Y Sayegh, O Delmas, R Itti, X Andrd-Fou~t Cardiological Hospital, 69003 Lyon - France. MYOCARDIAL SCINTIGRAPHY WITH TECHNETIUM-99m TEBOROXIME : COMPARISON WITH THALLIUM-201.

A comparative study between technetium-99m teboroxime (Cardiotec, Squibb) and thallium-201 has been performed in 30 patients (25 males, 5 females, age = 28-73 years) referred for myocardial perfnsion evaluation, with known or highly suspected coronary artery disease (coronary angiography available for 27 patients). In 18 cases there was a history of myocardial infarction (subacute n = 6, remote n---12). Exercise tests for both tracers were carried out during the same day on an ergometric bicycle with identical levels of exercise (105 +/-38 watts and 77+/-12% of maximal predicted heart rate for ~°lT1 vs 109+/-34 watts and 77+/-13% of MPHR for 99mTc-teboroxime). Images in three planar projections were recorded at stress and 4 hour-redistribution for 2°1T1 and reconstructed from a dynamic acquisition (10s/frame) at stress and rest for 99mTc-teboroxime using stress/rest (n=7) or rest/stress (n=23) protocols. Image analysis was based on a segmental model with 3 segments for each projection and tracer uptake was classified as normal or abnormal. Overall agreement between 2°1T1 and 99mTc-teboroxime was 73% (393/540 segments). Agreement for the anterior projection (82%) and for the LAO projection (74%) was better than for the lateral projection (63%). This latter result may be explained by intense liver uptake. For segments whose reading was in disagreement (147 segments) the majority (73%) showed abnormal 2°~TI uptake with normal 99mTc-teboroxime uptake.

FP-3D1-3 R. C. Hendel, B. A. McSherry, and J. A. Leppo. University of Massachusetts Medical Center, Worcester, Massachusetts, U.S.A.

THE DETECTION AND DIFFERENTIATION OF MYOCARDIAL ISCHEMIA AND INFARCTION BY TEBOROXIME COMPARED WITH THALLIUM (WITH AND WITHOUT REINJECTION) A good correlation between teboroxime (TEBO), a Tc-99m perfusion agent, and thallium (T1) for the presence of coronary artery disease has previously been reported. However, little information is available regarding the detection of ischemia (ISC) and/or infarction (INF), especially regarding vascular territory. Using a rapid planar imaging protocol, 54 patients (pts) underwent exercise TEBO and T1 studies. The two modalities were in agreement for the detection of coronary artery disease in 91% of pts (p<0.001). The concordance for the presence of INF or ISC was 70% and 82% respectively (p<0.01). Specific vascular territory abnormalities were concordant 83%, 85% and 83% for the LAD, LCX and RCA respectively (p<0.05). The total number of segments with ISC was 22% higher with TEBO than with TI. T1 reinjection was performed in 15 pts after the routine redistribution scan was obtained, and a similar number (n = 47) of ischemic segments were noted when compared with TEBO (n=53). In these same pts however, T1 redistribution images revealed only 36 ischemic segments. Thus, TEBO and T1 demonstrate excellent correlation for the detection of coronary artery disease and for the presence of INF or ISC in general or for specific vascular territory. The detection of more ISC by TEBO than with routine T1 imaging may represent a limitation of T1 redistribution imaging when compared to separate stress and rest (reinjection) studies.

FP-3D1-5 R.J. Burns, A. Fung, S. lles, R. Davies, L. Daigneault, L. Lalonde, and F. Hong Tai Eng. The Toronto Hospital, Vancouver General Hospital, Victoria General Hospital (Halifax), Ottawa Heart Inst. and Squibb Diagnostics Canada, Montreal, P.Q. EXERCISE Tc99m-TEBOROXIME CARDIAC SPECT: RESULTS OF A CANADIAN MULTICENTRETRIAL. Exercise Tc99m-teboroxime (TEBO) cardiac SPECT using single-head detector systems was compared to exercise thallium (T1201) SPECT in 66 patients (mean age 55, 52M/14F) performed within 2 weeks. Twenty-six patients also had coronary angiography within 3 months. Exercise TEBO imaging used 15-25 mCi and 18D-degree acquisition for 3-8 minutes with rest imaging (18-25 mCi) 60-90 minutes later. T1201 imaging used 3.0 mCi, 20 minute acquisition and 4-hour redistribution. Three blinded interpreters analyzed short-axis and vertical and horizontal long-axis tomograms to score 9 myocardial segments (apex; anterior, septal, i n f e r i o r and lateral - at apex and base) as normal, reversible, or fixed. Angiographic coronary artery disease (CAD) was defined as >70% diameter stenosis in primary (anterior descending, right, circumflex) or major secondary (diagonal, posterior descending, marginal) branches. Exact concordance of TEBO and Tl2Ol scores occurred in 460/594 (77%) myocardial segments (chi-square=116, p
539

Tuesday, 3 September 1991

FP-3D1-6

FP-3GI-1

C. Rossetti G. Vanoli, G. Paganelli, M. Kwiatkowski, F. Zito, F. Colombo, E. Deutsch and F. Fazio. Mallinckrodt Medical, Inc., St. Louis, Mo, ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy.

T. VANDER BORGHT, S. PAUWELS, L. LAMBOTTE, D. LABAR, S. DE HAEGHT, G. STROOBANDT, C. LATERRE. University of Louvain Medical School, UCL 54.30, av. Hippoerate 54, 1200 Brussels, Belgium.

EVALUATION IN HUMANS OF A NEW TRACER WITH OPTIMIZED PROPERTIES FOR MYOCARDIAL PERFUSlON IMAGING: [Tc-99m] Q12.

CEREBRAL MALIGNANCY WITH AND [lSF]FDG. We have previously shown that the evaluation of cellular proliferation can be noninvasively achieved by PET using [2JXC]Tdr. Applied to human brain tumours, the method could provide an aid in the assessment of the prognosis and the therapeutic response. In the present study, we have measured the [2-1lC]Tdr and [18F]FDG uptake in 7 patients with supratentorial tumours later proven by biopsy (3 glioblastomas, 1 astrocytoma, 1 anaplastic astrocytoma, 1 lymphoma and 1 adenocarcinoma metastasis). Immediately after injection of 2-8 mCi [2-Zl]Tdr (SA:33±5 mCi/~mole), PET scan was performed over a 60 min period, and arterial blood samples were taken throughout the study for determination of circulating total 11C activity as well as the volatile fraction (11C02). Thereafter, 5-10 mCi [IS]FDG were injected to evaluate glucose utilization according to the Stokoloff model. 0uantitative comparison of tumoral and contralateral regions, revealed in all cases an enhanced [2-11C]Tdr tumoral signal (from 6% in astrocytoma to 330% in lymphoma), whereas tumour glucose utilization was reduced in 4 cases. [2-ZZ]Tdr time-activity curves showed a maximal tumoral uptake within 5 min, followed by a two-phase clearance, a rapid exponential phase up to I0 min, and a very slow linear decrease similar to that found for blood zIC02. The present results indicate that [2-ziC]Tdr PET imaging allows the evaluation of DNA synthesis in brain tumours, even when proliferation rates are low. They also suggest that [2-1ZC]Tdr could provide a more sensitive and specific signal of tumour activity than [ISF]FDG.

Trans-(1,2-bis(dihydro-2,2,5,5-tetramethyl-3(2H)furanone-4methyleneamino) ethane) b i s ( 3 - m e t h o x y - l - p r o p y l ) phosphine) technetium-99m(lll), Q12, is a new nonreducible Tc(lll) cation being considered as a myocardial perfusion agent. After biodistribution and toxicity studies in animals, Q12 was evaluated in fasted, normal volunteers: 4 at rest and 1 at stress.After i.v. injection of 500 MBq of [Tc-99m] Q12 (radiochemical purity >95% by HPLC) anterior heart images were acquired in dynamic acquisition mode. Whole body biodistribution were evaluated at 1,2 and 5 hrs p.i. by the conjugate counting protocol; SPET images were acquired at 1.5 hrs. Blood and urine samples were collected up to 24 hours p.i. Q12 clears rapidly from the blood, exhibits rapid heart uptake (2% of i.d. at rest, 2.6% at stress) with no significant washout over 5 hrs. The bulk of the injected Q12 is rapidly cleared through the hepatobiliary system, while a significant amount (30%) is cleared through the renal system. In a comparative study the heart/liver ratios for Q12 and isonitrile (MIBI) are 1.6 and 0.3 respectively at one h p.i. The rapid hepatobiliary clearance reduces scatter artefacts and along with the lack of myocardial washout allows images acquisition within short time p.i. High renal clearance reduces the radiation burden to the patient. Thus Q12 has optimal imaging properties; it is now being evaluated in patients.

PET

STUDIES

OF

HUMAN

[2-1*C]THYMIDINE (TDR)

FP-3G1-2

FP-3G1-3

K.F. Hubner, G.T. Smith, M. Goodman, J. Thie, K. Hunter, A. Chan, and E. Buonocore. University of Tennessee Medical Center, Knoxville, Tennesee.

A Verha.qen, KG Go1, OE Nieweg2, G Luurtsema, MA Blankenstein3, TO de Groot, AMJ Paans and W Vaalburg Departments of Nuclear Medicine, Neurosurgeryl and Surgical Oncology2, University Hospital, Groningen and Department of Endocrinology3, Academic Hospital, Utrecht, The Netherlands

GRADING BRAIN TUMORS USING I-AMINOCYCLOBUTANE [C-II] CARBOXYLIC ACID (C-II ACBC) AND DYNAMIC PET SCANNING. F-18-FDG and C-ll-L-Methionine, co~nonly used to assess the metabolic/proliferative state of brain tumors, are also taken up by normal brain tissue resulting in relatively low tumor-to-nontumor concentration ratios. This study was done to determine if the unnatural, alicyclic s-amino acid ACBC might be useful for grading brain tumors. Twelve patients with suspected primary or recurrent brain tumors were examined, with FDG (N=II) and/or ACBC (N=I2). Data were acquired in dynamic scanning mode using an ECAT 931 (Siemens) after i.v. injection of 185-370 X 106 Bq of each radiotracer. PET scans were interpreted by visual inspection and ROI analysis in tumor, in contralateral grey and white matter regions and the skull. C-II ACBC dynamic ROI data were analyzed for time activity curve (TAC) profiles and standardized uptake values (SUV) and compared to histology and/or clinical followup. Results: (i) ACBC showed tumors with distinctly higher contrast than FDG. (2) There were seven true positive (TP), four true negative (TN) and one false negative (FN) ACBC scans. There were two FP and three FN FDG scans. (3) ACBC TAC profiles were variable. (4) The average was 0.25 in the TN and 1.65 in the TP cases. The average t u m o r - t o - n o n t ~ r ratios were 12.0 (ACBC) and 1.3 (FDG), and tumor to white matter ratios were 12.5 (ACBC) and 1.8 (FDG). Ccnclusion: (i) ACBC PET facilitates the diagnosis of primary and recurrent brain tumors, (2) SUV and TAC characteristics appear to be related to tumor grade. Further studies, especially a comparison to and correlation with C-ll-Methionine, are needed to validate ACBC for grading brain tumors.

540

UPTAKE OF A [18F]FLUORINE MENINGIOMA

LABELED PROGESTIN IN HUMAN

Epidemiological and clinical data indicate a steroid hormone sensitivity of human meningiomas. For example, the incidence of meningiomas is higher in women, the occurrence of meningioma may be associated with that of breast cancer, and the symptoms of a meningioma may aggravate during pregnancy. Progesterone receptors (PR) have been found at high concentration in many meningiomas. In addition, t h e presence of androgen, glucocorticoid, and mineralocorticoid receptors in meningioma has been reported. The presence of PR suggests that endocrine treatment of meningioma with anti-progestins may be of clinical use. For imaging PR with PET, we synthesized 21-[18F]fluoro16e-ethyl-19-norprogesterone ([18F]FENP). Our tissue distribution studies with normal rats and tumor bearing mice showed most promising results; [f8F]FENP is selectively taken up by PR containing normal and tumor tissues in vivo. In competitive binding assays unlabeled FENP demonstrates high specificity, competing only for PR and very little for binding to other steroid receptors. In a preliminary study, two patients with cranial meningioma were administered 0.6 mCi of [18F]FENP. At 40 and 90 min after injection, 20 min images were obtained with a ROTAPET tomograph. The system consists of a double-headed rotating system with two gamma cameras operating in a coincidence mode. In both patients high uptake of [18F]FENP was seen at the site of the meningioma. Ratios of radioactivity in the tumor to that in contralateral control tissue continued to increase during the specified period of time, suggesting that tumor uptake represents selective high affinity binding. The presence of PR in the biopsies of the tumors was confirmed by PR assay (>10 fmol/mg protein). This study suggests that [18F]FENP and PET may be useful in assessing PR and planning endocrine treatment in recurrent or inoperable meningiomas.

Tuesday, 3 September 1991

FP-3G1-4

FP-3G1-5

(3. Paganelli. G. Lucignani, P. Magnani, A. Zenorini, F, Sudati, G. Truci, M. Terreni, M. Giovanelli, F. Zito, C. Messa, H. Maecke and F. Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milano, Italy and University of Basel, Basel, Switzerland. A THREE STEP METHOD WITH ANTI-TENASCIN MoAb AND [Tc-99m]PAO-BIOTIN FOR THE DIAGNOSIS OF CEREBRAL GLIOMAS.

H Leversteinz, G van Don~en 2, JJ Quak z, HJM G Visser4, W den Hollander r, A van Lingen1, GJJ Teule 1, and G Snowz. Depts of Nuclear Medicinea, Otolaryngology (ENT) z, Pharmacy~, and Radio Nuclide Center 4, Free UniversityHospital, 1081 HV Amsterdam, The Netherlands 99mTe-E48F(ab')2 IN PATIENTS WiTH SQLIAMOUS CELL CARCINOMA(SCC) OF THE HEAD AND NECK

DIAGNOSTIC A C C U R A C Y O F

Tumor imaging within 3 hours after [In-111]DTPA-biotin injection has been reported with a 3-step method using an anti-CEA MoAb and the avidin/biotin system. Recently the imaging of gliomas has been achieved using radiolabelled MoAbs directed against tenascin, an extracellular matrix antigen. We have combined these two techniques and developed a 3-step method using an anti-tenascin MoAb for imaging cerebral gliomas. The anti-tenascin MoAb BC2 was biotinylated and 0.5 mg were administered i.v. in 8 patients with istologically documented glioma. After 3 days, 5 mg of cold avidin were injected i.v. followed 2 days later by i.v. injection of 0.2 mg of PAO-biotin labelled with Tc-99m (15-20 mCi). No evidence of toxicity was observed. Whole body biodistribution was measured at 20 rain, 2 and 3 h postinjection using a rotating gamma-camera and the conjugate view counting technique. Blood concentration of [Tc99m]PAO-biotin had a multiexponential clearance with a fast component (T1/2=2 rain) and a slow component (T1/2=110 min). [Tc-99m]PAO-biotin was primarily excreted through the biliary system. Three h after the injection 43% of the dose was in the liver and 15% in the urine. Tumors were detected in 6 of the 8 patients, using a brain dedicated SPET system, 60 min after the administration of [Tc-99m]PAO-biotin. These data suggest that [ T c - 9 9 m ] P A O - b i o t i n 3-step immunoscintigraphy may be used for the diagnosis and follow-up of patients with glioma.

The status of the cervical lymph nodes is the single most important prognostic factor in SCC of the head and neck. The superficial localization of these nodes may be favourable for immunoscintigraphy (IS). Our ENT laboratory developed the murine monoclonal antibody E48, only reactive with a cell surface antigen of stratified squamous epithelium and SCC. After indirect labeling (MAG3) of i mg MAb E48 F(ab')2 with 750 MBq 99mTc this antibody was administered to 10 patients with E48 antigen positive SCC of the head and neck and locoregional lymph node metastasis (N+). Immunoreactivity before and in plasma up to 48 hrs pi was always more than 70%. Whole body images and planar details of the neck were obtained 1, 16 (+SPECT), and 20 hrs pi: Optimal imaging was observed 16 hrs pi. All primaly tumors were detected by IS. Of all 21 lymph node regions with surgically proven metastases in the neck, 17 were found with MAb E48 of which 4 were missed by palpation, CT, and MRI. The 4 FN were smaller than 1 cm a n d / o r located near the mouth. Two of these spots were also missed by the other modalities. Three localizations were FP. Whole body images showed uptake of the radiolabel in the mouth/tonque, liver, gut, kidneys, and adrenals. There were no side effects and no HAMA responses up to 6 weeks pi. Conclusion: Immunoscintigraphy with 99mTc labeled MAb E48 of loco-regional lymph nodes in patients with SCC of the head and neck is vely promising. In order to decrease uptake by the tongue modifications of the radioimmunoconjugate are under investigation.

FP-3G1-6

FP-3HI-IA

B. O v e r b e c k , F. Gr~nwald, F. R o s a n o w s k i , B. Briele, C. v. I t t e r , H.J. B i e r s a c k . D e p a r t m e n t of N u c l e a r M e d i c i n e , ENT and R a d i o l o g y , Univ e r s i t y of Bonn, Germany

R. BEN YOUNE~, J. MAS, A. POUSSE, Laboratoire de B i o p h y s i q u e et Nucl@aire, Faeult6 de m 6 d e c i n e 25000 Besangon,France.

HMPAO-SPECT DURING CAROTID ARTERY COMPRESSION (MATAS-TEST) IN THE EVALUATION PRIOR TO CERVICAL TUMOR SURGERY WITH POSSIBLE CAROTID INVOLVEMENT For p l a n n i n g t h e s u r g i c a l approach in p a t i e n t s w i t h head and neck tumors w i t h s u s p e c t e d c a r o tid artery involvement the evaluation of the collateral b r a i n p e r f u s i o n is n e c e s s a r y p r i o r to carotid artery resection. We examined 10 p a t i e n t s w i t h n e c k - t u m o r s p e r f o r m i n g HMPAOSPECT d u r i n g c a r o t i d a r t e r y c o m p r e s s i o n . D u r i n g u l t r a s o u n d c o n t r o l l e d manual c o m p r e s s i o n of t h e i n v o l v e d common c a r o t i d a r t e r y T c 9 9 m - l a b e led HMPAO was i n j e c t e d . 6 p a t i e n t s showed a d e c r e a s e d p e r f u s i o n of t h e a f f e c t e d h e m i s p h e r e w i t h normal b a s e l i n e S P E C T - r e s u l t s and b a l l o o n occlusion tests. 2 of these patients underwent a carotid artery resection, one of t h e common c a r o t i d a r t e r y and one of t h e i n t e r n a l carotid a r t e r y . One p a t i e n t had a s i g n i f i c a n t perfusion deficit in t h e SPECT but no p a t h o l o g i c findings in a n g i o g r a p h y and b a l l o o n o c c l u s i o n t e s t . He s u f f e r e d from h e m i p a r e s i s p o s t o p e r a tively. The o t h e r p a t i e n t showed p r e o p e r a t i v e l y a m i n o r d e c r e a s e in p e r f u s i o n and had no neurological defects postoperatively. Our f i n d i n g s show t h a t t h e M a t a s - T e s t combined w i t h HMPAO-SPECT is a v a l u a b l e t o o l f o r r e o p e r a t i v e e v a l u a t i o n of b r a i n p e r f u s i o n . This t e c h n i q u e is not i n v a s i v e and can be p e r f o r m e d in e v e r y N u c l e a r M e d i c i n e d e p a r t m e n t w i t h an ECT-camera. HMPAO-SPECT w i t h t h e M a t a s - T e s t can add u s e f u l i n f o r m a t i o n or r e p l a c e i n v a s i v p e x a m i n a t i o n s .

R. BIDET de M @ d e c i n e

C O M P T O N S C A T T E R C O R R E C T I O N BY SPECTRAL ITERATIVE D E C O N V O L U T I O N (SID) The detection of Compton scattered p h o t o n s results in q u a l i t a t i v e d e g r a d a t i o n and q u a n t i t a t i v e i n a c c u r a c y of p l a n a r and S P E C T imaging . A n e w s c a t t e ~ c o r r e c t i o n m e t h o d b a s e d on iterative energy spectra deconvolution is presented. From list mode acquisition i n c l u d i n g e n e r g y ( 1 0 1 - 1 7 0 keV) for 99mTc, a set of e n e r g y images is derived. The p r o p o s e d SID technique extracts primary photons pixel per p i x e l by the use of an iterative d e c o n v o l u t i o n and a c o n s t r a i n t on the c o m p u t e d spectrum. On each iteration, each s p e c t r u m is c o n v o l v e d by the e n e r g y d e t e c t o r response. The r e s u l t i n g spectrum is obtained by multiplying the r e c o r d e d s p e c t r u m b y the r a t i o of the last result and the c o n v o l v e d one. This a l g o r i t h m a u t o m a t i c a l l y converges and works very fast. M O N T E C A R L O s i m u l a t i o n s d e m o n s t r a t e d the i m p r o v e m e n t of s e v e r a l p a r a m e t e r s b e f o r e a n d a f t e r scatter correction. F r o m the simulation, the original primary photons image was c o n t r u c t e d and was u s e d as r e f e r e n c e for the m e a s u r e d p a r a m e t e r s . L e s i o n d e t e c t a b i l i t y and spatial resolution improvement were demonstrated on Jaszczak's phantom and c l i n i c a l studies. This n e w t e c h n i q u e is the first step for a c c u r a t e q u a n t i f i c a t i o n in SPECT.

541

Tuesday, 3 September 1991

FP-3HI-IB

FP-3H1-2

~. B E N YOUNES,

J. MAS, A. POUSSE, R. B I D E T Laboratoire de Biophysique et de M~decine Nucl~aire, F a c u l t 6 de m ~ d e c i n e 25000 B e s a n c o n , F r a n c e .

K.Reichmann(*), C.R.Appledorn(**), H.N.Wellman(**), H . J . B i e r s a c k ( * ) ; (*) U n i v e r s i t y of Bonn, FRG, (**) I n d i a n a U n i v e r s i t y , I n d i a n a p o l i s , U S A

Q U A N T I F I C A T I O N IN SPECT BY R E S O L U T I O N AND A T T E N U A T I O N C O R R E C T I O N S

MEASUREMENT OF ENERGY AND SPATIAL DISTRIBUTION O F S C A T T E R I N G T O I M P R O V E I M A G E Q U A L I T Y IN S P E C T

SCATTER,

Quantitative i n f o r m a t i o n in S P E C T s t u d i e s is affected by scatter, spatial detector r e s p o n s e and p h o t o n attenuation. We a p p l i e d some o r i g i n a l p r o c e s s i n g methods w h i c h c o m p e n s a t e for t h e s e e f f e c t s . A set of energy images is d e r i v e d for each angular detector position (101-170 k e V for 9 9 m Tc) . S c a t t e r r a d i a t i o n is c o r r e c t e d by an i n n o v a t i v e s p e c t r a l i t e r a t i v e d e c o n v o l u t i o n m e t h o d (SID). This algorithm extracts from each projection p r i m a r y p h o t o n s p i x e l p e r p i x e l . The a c c u r a c y of r e s o l u t i o n and attenuation correction has been improved by a new method b a s e d on t h e generalization of iterative MOROZUMI's algorithm. These corrections n e e d the e n e r g y d e t e c t o r response, some m e a s u r e d p o i n t s p r e a d functions at v a r i o u s depths. They use our automatic contour detection and a constant a t t e n u a t i o n coefficient. Quantitation of a c t i v i t y concentration, lesion d e t e c t a b i l i t y and v o l u m e s were p e r f o r m e d b e f o r e a n d a f t e r all c o r r e c t i o n s . MONTE CARLO simulations and Jaszczak's phantom demonstrated the i m p r o v e m e n t of t h e s e p a r a m e t e r s for t h e corrected images c o m p a r e d w i t h the o r i g i n a l phantoms. R e s u l t s o b t a i n e d for c l i n i c a l studies show g r e a t e r b e n e f i t s of the a b s o l u t e q u a n t i t a t i o n after these corrections. Qualitatively, the resulting images match very well the c o r r e s p o n d i n g CT scans.

It is known, t h a t t h e p o i n t s o u r c e r e s p o n c e funct i o n (PSRF) c h a n g e s as s o u r c e p o s i t i o n is v a r i e d w i t h i n t h e i m a g e d s l i c e or v o l u m e . N o t as w e l l s t u d i e d is t h e v a r i a t i o n of t h e P S R F w i t h r e s p e c t to t h e e n e r g y w i n d o w e m p l o y e d . T h e c o n t r i b u t i o n of p h o t o n s u n d e r g o i n g C o m p t o n s c a t t e r i n g h a s t w o m a y o r i n f l u e n c e s on t h e d e g r a d a t i o n of i m a g e q u a lity in single photon emission comuted tomography: i) t h e c o n t r a s t of t h e r e c o n s t r u c t e d i m a g e is r e d u c e d and, thus, 2) s e m i q u a n t i t a t i v e v a l u e s are d e t e r i o r a t e d . W i t h t h e a i m of i m p r o v i n g i m a g e quality, we measured the energy spectral distribut i o n of p h o t o n s s c a t t e r e d in t h e o b j e c t w i t h i n a 140 k e Y + / - 10% w i n d o w . To a c h i e v e this, w e m e a s u r e d t h e e n e r g y d i s t r i b u t i o n of a T c - 9 9 m p o i n t s o u r c e in a i r a n d at 5cm intervals imbedded within a lucite scattering m e d i u m (solid c a s t block, 2 4 X 2 4 X 3 0 cm3). W e ass u m e d t h e d e t e c t e d c o u n t s Ni in t h e i - t h e n e r g y w i n d o w a r e t h e s u m of t h e s c a t t e r e d p h o t o n s N c i a n d t h e n o n s c a t t e r e d p h o t o n s Npi. As t h e r e is a b s o r p t i o n in t h e s c a t t e r i n g m e d i u m , t h e a m o u n t of s c a t t e r e d p h o t o n s is c a l c u l a t e d following N c i = N i - k * N p i , w h e r e k is t h e a b s o r p t i o n f a c t o r in t h e s c a t t e r i n g m e d i u m . The resulting spectra show the energy distribution of t h e s c a t t e r e d p h o t o n s w i t h i n t h e p h o t o p e a k . T h e a m o u n t of s c a t t e r e d p h o t o n s w a s 34% of t h e sum of t h e photons. T h e ratio of s c a t t e r e d p h o t o n s "left" t o w i t h i n t h e p h o t o p e a k v a r i e s w i t h i n t h e b l o c k b y m o r e t h a n a f a c t o r of 2.5.

FP-3H1-3

FP-3H1-4

M. Ivanovic, D.A. Weber, Brookhaven National Laboratory, Upton, NY,USA

G. MAUREL, J. SILVA, L. DUFLOT, A. JEJCIC, J. MAILLARD. Coll~ge de France ii, place M. Berthelot, 75005 PARIS, France.

MONTE CARLO SIMULATION CODE FOR SPECT IMAGING OF UNIFORM AND NONUNIFORMMEDIAAND SOURCEDISTRIBUTIONS. Monte Carlo simulations of SPECT imaging are used to analyze influence of the scatter on SPECT imaging and to evaluate accuracy ot the reconstruction algorithms. We adapted EGS4 simulation code for use with SPECT geometries that consisted of uniform and nonuniform distributions of water, lung and bone tissue. The EGS4 code is a very flexible and well documented code which allow the user to simulate electron and photon showers in any material. However, the user must write a subroutines to specify source distribution, object and detector geometry, and scoring routine for quantities of interest. To validate the simulation code 1) scatter fraction (SF), 2) line spread functions (LSF), and 3) energy spectra of the experimentally obtained and simulated data were compared quantitatively and qualitatively. The experimentally determined SFs for Tc-99m line source placed in the center of water filled cylindrical phantom 22 cm in diameter were in the range of 0.585 - 0.695 with a mean value of 0.63_+0.03 which agrees with the mean value of SF calculated from the simulated data of 0.63_+0,004. Experimentally measured FWHM and FWTM were: 9.7+0.1 & 18.9 +0.4 in water and 9.1+_0.1 &15.8+0.1 in air. The corresponding values calculated for the simulated LSF were: 10.0 + 0.1 & 19.1+0.5 in water and 92+0.3 &15.9_+0.3 in air. A qualitative comparison was made by applying peak height normalization to the simulated and experimental LSFs and overlapping them. A qualitative comparison of experimental and simulated energy spectra for a line source in water and in air show excellent agreement for energies greater than 120 keV. The calculated ratios of peak counts per energy channel to 'valley' counts per energy channel (at about 110 keV) were 2.2 in the measured and 2.3 in the simulated extrinsic spectrum. The same were 1.89 in the measured and 1,95 in the simulated intrinsic spectrum. The code provides an efficient approach to estimating energy and position properties of scattered photons for nonuniform source and attenuation media geometries. Research supported by DOE Contr. DE-aC02-76CH00016.

542

APPLICATION OF A CARLO SIMULATION DESIGN.

GENERAL PROGRAM

PURPOSE MONTE FOR DETECTORS

Simulation methods have a large interest, specially for collimators design. Because today, numerous specified detectors are developped. The use of the Monte Carlo method with particle tracking permit to take account of all interacting mediums (tissues, water, aluminium cover...). We propose to use GEANT, a program developped at CERN for elementary particle studies. This program supported by several sy3tems (VMS, UNIX), supply a large package for geometry design, and numerous graphical, statistical, interactive tools. The application of GEANT in Nuclear Medicine (NM) domain pose a specific problem. Because of the very high rejection level in detection with gamma-camera ( more than 999 for 1000 initial events), the use of that program is time consumming. It is the reason why we adapted GEANT on T-Node parallel computer. The speed gain is about i0/I with regard to VAX 6210 computer. To validate the program for NM applications, we simulate various commercial collimators. We appraise sensitivity and spatial resolution based on NEMA standard. The comparison with experimental results give a good aceuraccy. For example in sensitivity measurement, we compare high sensitivity ( H S ) and high resolution (HR) collimators. The sensitivity rapport HS/HR obtained by simulation is 2.96 and 2.90 from experimental results. We describe an optimised full purpose collimator with increased sensitivity and resolution. It may be usefull for large rectangular garama-camera, allowing to reduce the collimators handling.

Tuesday, 3 September 1991

FP-3H1-5 A. POUSSE, R. BEN YOUNES, J. MAS, R. BIDET B i o p h y s i c s & N u c l e a r M e d i c i n e Lab., 25000 B e s a n g o n - FRANCE

Q U A N T I T A T I V E 3D IMAGING BY SVD U S I N G A FEW N U M B E R OF PROJECTIONS. Q u a n t i t a t i v e m e a s u r e m e n t in S P E C T is not c u r r e n t l y a v a i l a b l e due to C o m p t o n scattering, poor spatial d e t e c t o r r e s o l u t i o n and photon b e a m attenuation. A direct r e c o n s t r u c t i o n m e t h o d is e v a l u a t e d in this work. It needs an a p r i o r i k n o w l e d g e of the attenuating medium geometry. A sampling virtual volume D is defined within the a t t e n u a t i n g medium. The r e c o n s t r u c t i o n of the radioactive distribution w i l l be p e r f o r m e d w i t h i n D. The w h o l e a t t e n u a t i n g m e d i u m p o i n t s p r e a d f u n c t i o n for e a c h D v o x e l and for each p r o j e c t i o n is acquired. The 3D r e c o n s t r u c t i o n of phantoms is p e r f o r m e d b y a p s e u d o - i n v e r s i o n technique. An a l g o r i t h m d e t e r m i n i n g the a d e q u a t e number of singular values used for the r e c o n s t r u c t i o n is suggested. The m e t h o d was t e s t e d on M O N T E C A R L O sim u l a t i o n s and on real p h a n t o m s . The q u a l i t y of the r e c o n s t r u c t i o n was s t u d i e d a c c o r d i n g to the number of p r o j e c t i o n s r a n g i n g from'3 up to 12. B e c a u s e of the v e r y large m e m o r y r e q u i r e ment, the c o m p u t e r time c o n s u m i n g and the great amount of a p r i o r i knowledge, such m e t h o d s have not e x t e n s i v e l y been s t u d i e d f r o m yet. However, their main advantage is t o simultaneously c o r r e c t for all i m a g e d e g r a d a t i o n phenomena u s i n g a few n u m b e r of p r o j e c t i o n s in o r d e r to a c c u r a t e l y determine local q u a n t i t a t i v e uptake.

FP-3H1-6 L. Bidautt,

J. Doll*, C. Als~, L.G.

Strauss*

ULB-H@pital Erasme, PET/Cyclotron, Brussels, Belgium * German Cancer Research Center, Heidelberg, Germany C O M P A R I S O N BETWEEN FILTERED B A C K P R O J E C T I O N AND A N E W ITERATIVE R E C O N S T R U C T I O N M E T H O D ON D A T A F R O M CLINICAL I N V E S T I G A T I O N S IN R O U T I N E POSITRON EMISSION TOMOGRAPHY "Standard" filtered backprojection and a recently developed iterative reconstruction m e t h o d w e r e c o m p a r e d on d a t a f r o m c l i n i c a l routine PET acquisitions. 18FDG data for homogeneous and spots phantoms, and for abdominal, heart, and brain studies (localization or metabolism) were a c q u i r e d on a f i f t e e n slices S i e m e n s / C T I Ecat 9 3 3 / 0 8 - 1 2 and r e c o n s t r u c t e d by both methods. The results were t h e n c o m p a r e d to figure out w h e r e b o t h m e t h o d s were r e s p e c t i v e l y standing, a s s u m i n g s t a n d a r d quality control procedures. After comparing "physical" results (homogeneity, r e s o l u t i o n / c o n t r a s t ) , we p r o v i d e examples of h o t / c o l d spot d e l i n e a t i o n and a r t i f a c t s removal ( p a r t i c u l a r l y for a b d o m i n a l studies), and finally compare the q u a n t i t a t i v e aspects by entering data from both r e c o n s t r u c t i o n s into a P a t l a k type m e t h o d and a model for b r a i n metabolism. W h i l e the iterative m e t h o d still t a k e s m u c h longer on the h a r d w a r e n o r m a l l y p r o v i d e d w i t h our camera, it p r o v i d e s b e t t e r c o n t r a s t in some cases and has i n t e r e s t i n g p r o p e r t i e s for handling hot/cold spot a r t i f a c t s . Besides e x p a n d i n g its use to the m o d e l i z a t i o n of d a t a c o r r e c t i o n , its q u a n t i t a t i v e a s p e c t s n e e d to be f u r t h e r investigated, in p a r t i c u l a r to a s s e s s h o w i n d e p e n d e n t t h e y r e m a i n f r o m the c o n v e r g e n c e criterion.

FP-311-1

FP-311-2

W. BECKER G. HORNEFF, A.SAPTOGINO, G.BURMESTER,F.WOLF Department of Nuclear Medicine and Institute of Rheumatology and Immunology ( Internal Medicine III ) of the University ErlangenNiJrnberg, FRG

J. Sciuk, K. S c h e i d h a u e r , W. Brandau, C. Pusk&s, O. Schober. Dept. of Nuclear Medicine, University of M u n s t e r , A l b e r t - S c h w e i t z e r - S t r a B e 33, Germany.

TC-99m-LABELLED HUMAN UNSPECIFIC IMMUNOGLOBULIN IN RHEUMATOID ARTHRITIS.

Tc-99m-labelled unspecific human immunoglobulin(HIG)was suggested as a new agent for the localization of inflammatory lesions. In this prospective study its value in rheumatoid arthritis was tested. 17 patients (juvenile rheumatoid arthritis n=2 ancylosing spondylitis n= 3; Reiter's syndrome n=l ; chronic rheumatoid arthritis n=12) were examined with 37-74MBq Tc-99m(children) or 2 0 0 555MBq Tc-99m labelled HIG. Gamma camera images (SIEMENS ROTA) of all small and large joints(44joints/patient) were performed lh, 4h, and 20h p.l.. 100000cts / frame were collected. (128x128) Disease activity and inflammatory activity was judged with the RITCHIE index(QUART. J. MED. 37(1968) 393-¢06)~ of ¢4- joints each. Swelling and pain was documented separately. Within of 8 days prior or after the HIG-scan a conventional three phase bone scan was performed. The gamma camera images 111/ Ch and 24h all presented comparable information. The Tc-99m-HIG uptake in 74-8 joints correlated well with clinical swelling of the joints(r=O.77"~r
D E T E C T I O N OF C H R O N I C O S T E O M Y E L I T I S LABELLED HUMAN IMMUNOGLOBULIN

WITH TC-99M

W e r e p o r t the use of T c - 9 9 m l a b e l l e d n o n s p e c i fic h u m a n i m m u n o g l o b u l i n (HIG) in d e t e c t i o n of c h r o n i c o s t e o m y e l i t i s (OM). Our study compares Tc-99m HIG and T c - 9 9 m l a b e l l e d m o n o c l o n a l m o u s e a n t i b o d i e s (MAB). 17 p a t i e n t s w i t h s u s p e c t e d c h r o n i c OM in 20 l o c a t i o n s w e r e examined. 4 and 24 hrs a f t e r i . v . - i n j e c t i o n of 500 M B q T c - 9 9 m HIG, s c i n t i g r a p h i c i m a g e s w e r e a c q u i r e d u s i n g r o u t i n e g a m m a cameras. A c o n t r o l s t u d y a f t e r i . v . - i n j e c t i o n of 500 M B q T c - 9 9 m M A B was p e r f o r m e d w i t h i n 3 days. T h e final d i a g n o s i s w a s e s t a b l i s h e d b y o p e n s u r g e r y in all cases. 14/20 l e s i o n s w e r e p r o v e d t o b e -chronic OM, 6 of t h e m l o c a t e d in p e r i p h e r a l areas, 8 of t h e m in c e n t r a l areas. 6/20 l e s i o n s w e r e n o n - i n f e c t i o u s . In p e r i p h e r a l O M H I G was s h o w n to be t r u e pos i t i v e in 5/6 and M A B in 6/6 cases. In c e n t r a l O M H I G was t r u e p o s i t i v e in 5/8 and M A B in 0/8 cases. All' 6/6 p a t i e n t s w i t h n o n - i n f e c t i o u s l e s i o n s w e r e t r u e n e g a t i v e w i t h b o t h studies. The r e s u l t s s h o w s u p e r i o r i t y of M A B in p e r i p h e r a l OM. In c e n t r a l a r e a s H I G s e e m s to b e m o r e s e n s i t i v e c o m p a r e d to MAB. H I G m i g h t d e t e c t e v e n c e n t r a l O M as p h o t o n r i c h l e s i o n in r e l a t i o n to its low p h y s i o l o g i c a l u p t a k e in a c t i v e b o n e marow, w h i l e M A B l e a d s to a non s p e c i f i c c o l d l e s i o n w i t h i n its p h y s i o l o g i c a l h i g h u p t a k e in a c t i v e b o n e marrow.

543

Tuesday, 3 September 1991

FP-311-3

FP-311-4

G.S. L i m o u r i s , B. D u l i , O . Fronistas, A. Giougi, M. Toubouros, A. Stavraka.

D. Sandrock, B. Kolthoff, and D.L. Munz. Department of Nuclear Medicine, Georg University, G~ttingen, Germany.

Nucl Med Sec, A r e t e i o n Univ Hospital, Athens Med School Tc-99m-LABELLED H U M A N I M M U N O G L O B U L I N : A NEW A G E N T FOR I N F L A M M A T O R Y JOINT SCINTIGRAPHY The radionuclides available recently for inflammation Iocalization~ present each one separately a lot of problems and a major disavantage the lack of s p e c i f i c i t y . T c - 9 9 m labelled human polyclonal IgG is introduced as a new more specific agent f o r i n f l a m m a t i o n imaging.

All patients examined (4 women aged 32 to 54 years, and 18 men aged 21 to 57 years) were i n f o r m e d of the procedure and gave t h e i r consent. 555 MBq (15 mCi) T c - 9 9 m - M D P ( M E D G E N I X - B E L G I U M ) and 555 MBq (15 mCi) Tc-99m-FilG (MALLINCKRODT DIAGNOSTICA) images were both obtained f o r each patient w i t h i n a m a x i m u m delay of four days. Tc 9 9 m - M D P dynamic acquisition scan was f i r s t p e r f o r m e d to provide i n f o r m a t i o n about perfusion in the suspected area, f o l l o w e d by 2.5 h delate planar scintifotos. Tc-99m-HIG static images were obtained 4-6 h a f t e r the i.v. application. Additional 24 h images were made f o r comparision. Five patients with proven osteoarthritis~ eleven w i t h proven matastases (four due to breast and seven due to prostate cancer) three with recent bone f r a c t u r e and three w i t h o s t e o m y elitis were included in this t r i a l . T c - 9 9 m - M D P scans were positive in all cases. T c - 9 9 m - H I G scans were positive in all cases with a b e t t e r picture quality compared with those of T c - 9 9 m - M D P , except the cancer a f f e c t e d patients. All bony m a t a s t a t i c cases were negative. in this study we report the a p p l i c a b i l i t y of T c - 9 9 m - H I G as a new agent~ more specific in detecting muscleskeletal i n f l a m m a t i o n compared w i t h T c - 9 9 m - M D P . We evaluate its almost unique usefulness in the d i f f e r e n t i a l diagnosis of suspected but not proved bony metastases.

IMPROVED IMMUNOSCINTIGRAPHIC INFLAMMATORY BONE LESIONS.

METHOD

August

FOR DETECTION

OF

Objectives ef this study were to compare immunoscintigraphy (IS) with antigranulocyte antibody (AGAb) with a double-tracer subtraction scintigraphy and a kinetic uptake analysis for detection of florid grsnulocytic loci in areas harboring hematopoietic bone marrow. IS was performed 4 and 24 hours after injection of 555 MBq Tc-99m labeled monoclonal AGAb BW 250/183 and 30 min after 370 MSq Tc-99m microcolloid (MC) in 58 patients (29 men, 29 women, age 17 - 82 years) with suspected inflammatory lesion in areas with hematopoietic bone marrow (spine or bones/soft tissue of upper and lower limb). Final diagnosis was confirmed by cytology/histology/bacteriology (golden standard) up to now in 31 cases. For subtraction seintigraphy the 24 hr AGAb image and the 30 min MC image were used as described previously (J Nucl Med 31:1589). Kinetic uptake analysis compared tracer aeeumulatien in the lesion, adjacent background and adjacent spine or eontralateral limb, respectively. Overall, 6 inflammatory loci of spine and 25 of the limbs were analyzed. Merely visual reading of 24 hr AGAb image yielded a sensitivity of 83 % and a specificity of 85 %. Subtraction scintigraphy was superior in 3 cases (limbs) resulting in a sensitivity and specificity of 92 % each. Comparison of 24 and 4 hrs p.i. background corrected lesion to contralateral limb/adjacent spine ratio showed an increase in all proven inflammatory foci and no false positive finding resulting in sensitivity and specificity values of 100 % each. In conclusion, kinetic uptake analysis is superior to only visually analyzed images with AGAb or MC alone or the subtraction~reverse subtraction approach for localization of florid granulocytic inlammatory foci.

FP-311-5

FP-3D2-1

P.Lind, B.Hausmann*, P.K61tringer, R.Passl*, O.Eber, Barmherzige Briider Eggenberg Hospital, Nuclear Medicine, *Department of Accident Surgery Graz, Austria

H.Feistel, K.Goehl, K.Bachmann, F.Wolf D~partments of Nuclear Medicine and Medicine II (Cardiology), Friedrich- Alexander- University Erlangen- Nuernberg , Erlangen, FRG

ANTI-GRANL~OCYTE IMMUNOSCINTIGRAPHY (MAb BW 250/183): CLINICAL EXPERIENCE AFTER SINGLE AND REPEATED APPLICATION OF INTACT MURINE IgG I Antigranulocyte immunoscintigraphy with a Te-99m labeled monoclonal antibody (MAb BW 250/183) was performed in 159 patients. In a group of 130 patients a single dose of 0.5 mg antibody (550 MBq Tc-99m) was administered in order to prove or exclude inflammatory processes. In another group of 29 patients with complicated bone fractures 0.3mg antibody (550 MBq Tc-99m) was administered 7, 49 and 91 days after fracture in order to show the behaviour of leukocytes with different kinds of surgical treatment. Planar and/or SPECT imaging (Elscint Apex 409 AG Haifa/Israel) was done 6 and 24 h or 18 h post injection of 0.5 mg and 0.3 mg MAb BW 250/183 (Behring Werke Marburg, FRG), resp. HAMA values (Behring Werke, Marburg/FRG) were determined before and 12 weeks after single application of 0.5 mg in 29 patients and before, 3 and 6 weeks after repeated application of 0.3 mg antibody in 29 patients resp. For identification or exclusion of leukocytic inflammation sensitivity (92%) and specificity (88%) of antigranulocyte immunoscintigraphy were very high. After single application of 0.5 mg intact IgG 1, 4 out of 29 patients developed HAMA. In the bone fractur group the highest leukocytic infiltration was seen in patients with external fixation. In most patients the leukocytic infiltration returned to the upper normal value 12 weeks after fracture, except in case of secundary soft tissue abscesses or osteomyelitis. After repeated application of 0.3 mg antibody, 2 out of 29 patients developed HAMA after the first application and 15 out of 29 patients after the third application. In conclusion, antigranulocyte immunoscintigraphy is an easy, quick and save method to detect leukocytic inflammation. In patients with bone fracture, there is an inverse correlation between granulocyte accumulation and the stability of the fracture.

544

CONGENITAL MYOCARDIAL SYMPATHETIC DYSINNERVATION- A STRUCTURAL DEFECT OF IDIOPATHIC LONGQT SYNDROME DETECTED BY MEANS OF 1-123-MIBG SPECT For more than two decades an imbalance in the sympathetic innervation of the myocardium has been postulated as a cause of the long- QT syndrome (LQTS). Twelve members of four LQTSfamilies (mean a@e 38y) and eight healthy normals were studzes by means of 1-123- mIBG SPECT. A semiquantita£ive analysis was performed in all scans, those of the normals showed a uniform tracer uptake. Uptake ratios of heart, lung, mediastinum and liver were determined by planar technique. From the 12 family test patients 5 showed a LQTS. All patients with QTc>440 ms. all who had suffered from at least one episode of cardiac arrest or ventricular fibrillation and all patients with QT- prolongation had reduced or abolished mIBG- uptake (p<0.02) in the inferior and septal parts of the left ventricle. Additionally one female without symptoms and LQTS showed an abnormal mIBG SPECT slmilar to that of her daughter, who had symptoms and LQTS. One father without symptoms develloped LQT during cardiac stress ECG, his son showed symptoms without LQTS and had an abnormal SPECT. All members with normal mIBG SPECT had neither LQT nor symptoms. The results show that LQTS is only a contingent symptom of a superior "congenital myocardial s~/mpathetic dysinnervation (CMSD)", which fullfzlls the criteria of an autosomaldominant inheritance. Patients with CMSD must undergo further therapeutic treatment, their families must be submitted to family screening.

Tuesday, 3 September 1991

FP-3D2-2 g . L e k a k i s , N.Vassilopoulos, D.Tsinikas, Ch. Papamichael, A.Vidanopoutos, d.Nanas, Ch. Palaistides~ P.Kostamis, S.Moulopoulos. Dept of Clin TherapeuLics and Depk of Nuclear Medicine Alexaedra University Hospital, Athens. CARDIAC ADRENERGIC INNERVATION ABNORMALITIES IN PATIENTS WITH DILATED CARDIOMYOPATHY: STUDY BY 1-123 HE[AIODOBENZYLGUANIDINE. Abnormalities of adrenergic innervation in myoeardium of p a t i e n t s ( p t s ) with d i l a t e d cardiomyopathy (DCM) have been r e p o r t e d . 1-123 Hetaiedobenzylguanidine (MIBG) is s guanethidine analogue u s e f u l in d e l i n e a L i n g myocardial sympaLheLic i n n e r v a t i o n . To study the p a t Lern of 1-123 MIBO imaging in DCH pLs, we examined 13 DCM pts and 15 normaI controls. Mean ejection Fraction in pLs was 26±12Z and coronary arteries were normal by aegiography. SPECT Ti-201 imaging aL rest was abnormaI in 2/13 pLs and 0/15 controls. 1-123 MISS SPECT imaging was performed I and 2 hours after injection of 5 mCi [-123 MISC. I verLical and 4 shorL axis views were analyzed and variation in 1-123 MIBG disLribution >25% was characterized as nonhomogenous uptake. 9/15 controis showed reduced upLake to Lhe apex while 13/13 DCM pLs had s nonhomogeneous paLtern with muILiple areas of reduced uptake. Washout taLe between Ist and

2rid hour was reduced in c o n t r o l s compared to pts (16±18%vs 28±19Z p-O.05) buL s i g n i f i c a n L o v e r l a p p i n g o f values was observed (3 pts washout t a l e < 2SZ, 2 cont r o i s washout t a l e >2OZ. In conctusion 1) DCM pts presenL a noehomegeneous patLern o f 1-123 MIBG uptake, compleLely d i f f e r e n t Lhan thaE observed in c o n t r o l s . 2) Washout r a t e o f 1-123 MIBG is increased in DCM pLs.

FP-3D2-3 W. H. Knapp. A. Bentrup, U. Schmidt, G. Notohamiprodjo, B. Heesing, H. Schmidt, D. Fagbender Institute of Nuclear Medicine and Department of Cardiology, Heart Center North-Rhine Westphalia, Bad Oeynhausen, FRG.

ASSESSMENT OF MYOCARDIAL VIABILITY IN POSTISCHEMIC AKINESIA WITH In-111-ANTIMYOSINANTIBODIES (AMAB) AND Tc-99m-MIBI The clinical success of mechanical recanalisation after infarction and lysis is determined by the extent of necrosis and that of jeopardized (viable) myocardium. Since akinesia can be due to either condition, this study was undertaken to evaluate the potential of AMAB and MIBI for the assessment of the functional state of postischemic myocardium. In 43 patient 2.5 mCi AMAB and 15 mCi MIBI were injected 1-8 d post acute ischemia. AMAB scintigraphy was carried out 48 h p.i., MIBI ECG-gated acquisition 1 h p.i. with subsequent Fourier-analysis for wall-motion display. 22 patients had significant AMAB accumulation corresponding to or exceeding the perfusien defect (A), 10 patients showed despite aldnesia - neither significant AMAB myocardial accumulation nor a significant perfusion deficit (B) and in 11 patients a perfusien deficit matched akinesia, however, there was no AMAB accumulation (C). Clinical findings: enzymatically and/or electrophysielogically proven previous infarction in 21/22 patients of group A, in 1/10 pts. of group B and in 5/11 pts. of group C; angina in 1/22 pts. of group A, in 4/10 pts of B and in 6/11 pts. of C. Follow-up angiography: improvement of LV-function in 1/5 pts. of group A and in 7/7 pts. of B. 4 pts. of group C had remote infarctions. (A) indicates that akinesia is due to extended necrosis and that improvement of LV-functien is unlikely, (B) indicates myocardial stunning and (C) remote infarction or severe rest ischemia. The combined AMAB and MIBI scintigraphy adds to the pathophysiological interpretation of pest-ischemic akinesia and helps selecting the adequate therapy.

FP-3D2-4 I.Carri6, L.Bern~, M.Estorch, G.Torres, C.Duncker, D.Duncker, M.Bal]ester, D.Obrador. H o s p i t a l de S a n t Pau, B a r c e l o n a , S p a i n .

FP-3D2-5

R I S K OF REJECTION RELATED COMPLICATIONS AFTER HEART TRANSPLANTATION ASSESSED BY ANTIMYOSIN ANTIBODY STUDIES.

ACCURATE DIAGNOSIS OF ACUTE DEEP VENOUS THROMBOSISWITH TECHNETIUM-99m ANTIFIBRIN SCINTIGRAPHY IN SYMPTOMATIC PATIENTS: RESULTS OF PHASE III CLINICAL TRIAL

We p e r f o r m e d 201 I n - 1 1 1 a n t i m y o s i n antibody studies coinciding with right ventricular endomyocardial biopsies i n 43 p a t i e n t s 1-64 months after transplantation. A heart to lung ratio (HLR) was u s e d as a m e a s u r e o f r e l a t i v e antimyosin uptake. 129 s t u d i e s coincided with absent rejection at biopsy, 25 w i t h m i l d , and 47 w i t h m o d e r a t e . HLR was 1 . 6 4 ± 0 . 2 8 , 1 . 7 8 ± 0 . 2 4 and 1 . 9 6 ± 0 . 3 4 in the 3 biopsy groups respectively (p
Thomas F. Schaibls, Patrick Peltier, Jean-Luc Mortelmans, Alain Bertrand, Herbert Ehringer, and the Antifibrin Multicenter Group, Centocor, Inc., Malvern, PA, USA.

Initial studies with technetium-99m labeled T2GIs antifibrin Fab' murine monoclonal antibody (Tc-AF) have shown a high rate of detection of acute deep venous thrombosis (DVT). To prospectively evaluate the diagnostic performance Sf Tc-AF in patients with suspected DVT, 153 patients with signs and/or symptoms of acute DVT were injected with 0.5 mg AF labeled with 15-20 mCi Tc-99m. Images of the legs were acquired immediately post-injection, at 90 min., and at 4-6 hr. Acute DVT was confirmed by contrast venography (CV) performed within 24 hrs after Tc-AF. Tc-AF images were evaluated by a blinded panel of nuclear medicine specialists using criteria based on dynamic localization of the Fab'.- Overall diagnostic sensitivity was 80% (54/68) and specificity was 82% (70/85) (likelihood ratio = 4.5). Howe~er, in patients in whom Tc-AF detected proximal vein DVT, where patients are at greatest risk for PE, the likelihood ratio was 22.8, i.e. the odds of proximal DVT increased 22.8 times with a positive scan. In patients who had a prior history of DVT, sensitivity was 100% (15/15) and specificity was 88% (15/17). Injection of Tc-AF was well tolerated in all patients. Positive human antimouse antibody responses occurred in 2.5% of patients. Thus, Tc-AF is an accurate, yet safe, diagnostic test for acute DVT, enabling non-invasive assessment of acute DVT above and below the knee in both legs with a single procedure. In addition, it is highly accurate in acute recurrent DVT, a condition often difficult to diagnose by both invasive (venography) and non-invasive (doppler/ ultrasound, impedance plethysmography) methods.

545

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Tuesday, 3 September 1991

FP-3D2-6 M.Clausen, E.Henze, P.Weism011er, R.Weller, M.Kochs, J.Steinmann, E.Miller-Schneider, A.Schmidt, T.Eggeling, M.J~gg, J.Mester (i), R.0chsenk0hn, V.Hombach, W.E.Adam Nuclear Medicine, Cardiology, University Ulm, Germany (1) Nuclear Medicine, University Szeged, Hungary DOUBLE-ANGULATED INTEGRAL-SPECT (ISPECT) OF THE CARDIAC BLOOD POOL FOR DETECTION OF ARRHYTHMOGENIC SUBTRATES. Phase analysis of radionuelide ventriculography (RNV) may detect the site of initial contraction (SIC) in one left anterior oblique view. The purpose of this study is to modify gated SPECT in order to obtain 3 views aligned to the long axis of the heart and with little overlap between the ventricles. 32 angles are acquired over 180 degrees with 8 frames per cardiac cycle. The Fourier coefficients of the first harmonic are backprojected, doubleangulated according to the cardiac axis and integrated containing all of the ventricles in one thick slice. Finally the phase (and amplitude) is calculated and displayed as short and long axis views and as the 4-chamber view. The earliest phases are classified as SIC. 21 patients were investigated: 2 with pacemakers, i0 WPW-syndromes (7 electrophysiologically proven) and 9 ventricular tachycardias (VT). All SIC coincide exactly with the eleetrophysiological information except: in 2 WPW-syndromes a second Kent bundles is not visualized, in 1 V T there is a discrepancy of 3 cm. The detection of the SIC by ISPECT depends on several factors: Kent bundles only with antegrad conduction are seen; an increase in preexcitation will increase the lesion contrast; lesions with lateral location are preferred and are easier differentiated from the physiological pathway; in VT the electric and mechanic focus does not have to coincide (for pathophysiological reasons). In addition to surface-ECG arrhythmogenic substrates will be confirmed and localized more precisely by using ISPECT~ thereby helping to streamline subsequent invasive procedures.

FP-3G2-1 U Haberkorn, V Rudat, F Oberdorfer, T Klenner, M St6hr, R WaUich, A Altmann, A Dimitrakopoulou, LG Strauss Institute of Radiology and Pathophysiology, German Cancer Research Center, H~idelberg THERAPY INDUCED CHANGES IN GLUCOSE UPTAKE, GLUCOSE TRANSPORTER GENE EXPRESSION AND CELL PROLIFERATION IN A OSTEOSARCOMA MODEL. Cisplatinum therapy of the human osteosarcoma is often complicated by severe side effects. Therefore several diphosphonate compounds have been developed as tumor seeking agents and are now tested in a rat osteosarcoma model with substantial similarities to the human tumor. We used 2 cell lines derived from a lung metastasis of this tumor and 3 drugs: cisplatinum and two phosphonate compounds (AMDP, DADP). The cells were incubated 4 hours in a drug containing medium. Therapy induced changes were measured 1 and 24 hours after therapy. The C-14-FluoroDeoxyglucose (FDG) and FDG-6-Phosphate concentration was determined after 5 and 60 min. incubation in a glucose-free medium (1 pCi FDG/ml) with high performance liquid chromatography. Two-dimensional flow cytometry was used to measure the cell cycle fractions in controls and treated cells. The glucose transporter (GT) gene expression was determined by Northern blotting and hybridization with a cDNA probe against the GT mRNA. One hour after therapy the FDG uptake showed a 16% decrease in AMDP and DADP treated cells and 10% in cisplatinum treated cells; flow cytometry revealed no significant changes in the cell cycle fractions. One day after therapy, the cells were blocked in the G2/M phase as shown by flow cytometry. However, no further significant change in FDG uptake was seen. These data were compared to the GT mRNA transcription. Our results show, that the glucose uptake is a very sensitive parameter for therapy induced changes even for low therapeutic doses.

FP-3G2-2

FP-3G2-3

W. Maschek and K. Bosslet Institute for N u c l e a r m e d i c i n e , Linz Behring R e s e a r c h Labs, Marburg, FRG

A. B i s c h o f D e l a l o y e , B. D e l a l o y e , F. B u c h e g g e r , A. P ~ l e g r i n , Ch. H e u s s e r , N. H a r d m a n n , J.P. M a c h , L a u s a n n e U n i v e r s i t y and C I B A G e i g y Ltd, B a s e l S w i t z e r l a n d

IMMUNHISTOCHEMICAL CHARACTERIZATION OF THE CDRGRAFTED HUMANIZED MONOCLONAL ANTIBODY BW 4 3 1 / 2 6 (huMAb) - PRECLINICAL STUDY

I m m u n o s c i n t i g r a p h y with Tc-99m labelled murine m o n o c l o n a l a n t i - C E A antibody BW 431/26 (muMAb) is an e s t a b l i s h e d method for d e t e c t i o n of CEA producing tumours. HuMAb was produced by standard r e c o m b i n a n t t e c h n i q u e s (GOssow and Seemann, 1991). P r o b l e m s of high u n s p e c i f i c b a c k g r o u n d staining arize, if t r a n s f e c t o m a s u p e r n a t a n t s c o n t a i n i n g huMAb are e v a l u a t e d using the i n d i r e c t APAAP staining t e c h n i q u e on human t i s s u e s due to endogenous human Ig. To inhibit u n s p e c i f i c binding of second a n t i b o d y on c r y o s t a t sections of human tissues a p r e i n c u b a t i o n - i n h i b i t i o n test was developped. Using this test the s p e c i f i c i t y of muMAb and huMAb was compared on various normal human tissues (n=3g) as well as on CEA and non-CEA e x p r e s s i n g tumours (n=30). No differences were observed. Summary: 1. HuMAb detects the same epitope on cell bound CEA as muMAb. 2. The p r e i n c u b a t i o n i n h i b i t i o n test permits the s p e c i f i c i t y analysis of u n p u r i f i e d huMAb derived from t r a n s f e c toms s u p e r n a t a n t s on human tissues. 3. Because of the s i m i l a r i t y between huMAb and p o l y c l o n a l human Ig no HAMAs should be produced.

546

I M M U N O S C I N T I G R A P H Y (IS) W I T H C H I M E R I C A N T I C E A MAB: A P R O S P E C T I V E S T U D Y IN P A T I E N T S WITH POSSIBLE RECURRENCE FROM COLORECTAL CARCINOMA. T h i s s t u d y w a s p e r f o r m e d in o r d e r to a s s e s s the d i g a n o s t i c v a l u e of IS w i t h 1-123 l a b e l e d c h i m a e r i c a n t i - C E A M A b in p a t i e n t s w i t h r a i s i n g C E A levels (2-176 ng/ml, m e a n 45) as u n i q u e s i g n of p o s s i b l e r e c u r r e n c e of c o l o r e c t a l c a r c i n o m a . In 16/19 p a t i e n t s (aged 44-81, m e a n 61 yrs) s t u d i e d 1,6,24 h a f t e r i n j e c t i o n b y p l a n a r v i e w s a n d ECT the f i n d i n g s of IS w e r e c o m p a r e d to simultaneous and subsequent diagnostic w o r k u p and c o r r e l a t e d to f o l l o w - u p (5) or s u r g e r y (Ii). 3 p a t i e n t s w e r e c o n s i d e r e d as t u m o r free, ii h a d one, 2 m u l t i p l e sites involved (i0 l o c o r e g i o n a l , 5 liver, 3 m i s c e l l a n e o u s ) . IS s h o w e d 8/10 l o c o r e g i o n a l r e c u r r e n c e s (2FP) and 4/5 l i v e r m e t a s t a s e s (2FP), c o n v e n t i o n a l m e t h o d s 2/10 l o c o r e g i o n a l and 1/5 l i v e r lesions, as w e l l as 1 a d r e n a l m e t a s t a s i s a n d 1 p a r a a o r t i c node. O v e r a l l d e t e c t i o n a n d e x c l u s i o n r a t e s a n d a c c u r a c y w e r e 0.78, 0.79, 0.78 r e p e c t i v e l y for IS a n d 0.28, 0.95, 0.62 for the c o m p r e h e n s i v e w o r k u p . Due to t h e l o w e r i m m u n o g e n i c i t y of c h i m a e r i c w i t h r e s p e c t to murine MAb and good imaging properties this a p p r o a c h s e e m s to o f f e r a s e n s i t i v e tool for the f o l l o w - u p of p a t i e n t s w i t h colorectal carcinoma.

Tuesday, 3 September 1991

FP-3G2-4

FP-3G2-5

SgR[':CNI I':, MAH"DI,I I,, CRIPPA ~", GASPARINI M, [IOMBARII,It,',I~I ~l. CASTI%IANI MR, GIANNi MC', MASSIMINOM ', BURAGGICI.

]. M ichelot ~ A..Veyr e ~ ].Bonafous~ , **~M'F" Moreau~.~, J.C. M a d e [ m o n t p. L a b a r r e , [+. Lapalus F,..Bacin P. So u t ey.rand , R. Plagne , G.Gaillard ~,.INSE R M U 71 Centre 3. Perrin Clermont-Ferrand~ Centre A. L acassagne~Nice, CHRU C l e r m a n t - F,er rand, F,r a n c e . PHASE 2 S C I N T I G R A P H I C STUDY OF M A L I G N A N T M E L A NOMA ( M M ) AND METASTASES WITH 125-1ODINE N-(ZDIETHYLAMINOEIHYL) 4-10DOBENZAMIDE We r e p o r t the results of the c l i n i c a l t r i a l e v a l u a t i n g N - ( 2 - d i e t h yla m ina eth yt) 4-[odobenzamide or BZA as an 02/14/1989, imaging agent of MM (Brevet n°8901898, F r a n c e ) . 78 i n v e s t i g a t i o n s were p e r f o r m e d in 70 i n f o r m e d patients (age 3 5 - 8 9 yrs) c l a s s i f i e d as f o l l o w : Group I n = 14 C u t a n e o u s and o c u l a r , p r i m a r y m e l a n o m a . G r o u p l l n : 27 M e t a s t a s i s and r e c u r r e n c e of MM ( d o c u m e n t e d melanoma lesions). Group ill n = 32 C o m p l e t e clinical remission~ f o l l o w up of p a t i e n t s a f t e r L r e a t m e n t of M M . Group iV n = 5 Non m e l a n o m a p a t h o l o g y . ]ma~%~ were p e r f o r m e d aL 6 and 24 hr a f t e r i.v. i n j e c t i o n of I-BZA (10 rag, 187 MBq), CIS B i o i n d u s L r i e s . A n t e r i o r and p o s t e r i o r whole body images, static images and L o m o s c i n t i g r a p h y we~e192~tainedThe I - B Z A i m a g i n g studies were c o m p a r e d to the results of the c l i n i c a l examination and o t h e r i m a g i n g methods. SC[NTICRAPHY Positive Negative known unknown Group I I~/14 1 Group II 30/51 18 21 Group Ill O 0 33 Group IV 0 0 5 This study v i s u a l i z e d 50 out of 51 known metastases and recurrences. 18 o c c u l t metastases were detected. The confirmation of t h e i r n a t u r e was o b t a i n e d by C T , u l t r a sound, p l a n a r r a d i o g r a p h y or biopsy. S e n s i t i v i t y is 70 %, no false p o s i t i v e was o b s e r v e d . We c o n c l u d e d t h a t 1251_BZ A seintigraphy is a prsmising~ sensitive technique for the e v a l u a t i o n and d i f f u s i o n of M M , p a t h o l o g y which r e p r e s e n t s a d i f f i c u l t diagnosis p r o b l e m .

Nuclear Medicine I)jv and ~ Paedial,ric Oncology Oiv Na/J0nal Cancer Insl,ihffe Milan II,aly

PRI,:I,IMINARY }{I':SU[:fS OF }{ADI01MMUNOSC]NTICRAPHY0F PA[':DIATRIC IdlABI)OMYOSARCOMA Idlabdomyosareonla (RMS) is a rare and a~gressive turnor in infanls and ehiNren. Aim or the sLudy is l-o evaluaLe the feasibi]ity of seintJ~raphJc ima~in~ with anl,imyosin radiolahelted n/onoelonal antibodies. These antibodies, nurrenUy used in cardiologieal nuclear medicine, are monovalen[ fragments (RIII)IO) supphed by Centocor, and labelled with bO IO0 Mtlq or Indium I I I chloride (Amersham ]nl,) according wil,h rnanufantnrer insLrael,ions. Heven pl,s (with RMS of head, neck

and pelyis) cnlercd our' study: 7 with primary well documented (Computed Ton/ography, Magnetic Resonance, Immunohistoehemistry) uubeaked RMS, d with no evidence of disease after surgical and theme radio kherapie treatment. Age ranged between 7 and 16 years. I,abclled antibodies (50 70 Ml]q) were slowly i.v. injeeLcd in each patient and in one pal,ienL l,he study was repeated aft,or therapy: no

pal,ienl, presented any adverse reaction l'o adminisl,ration. hnages were collected 24 and 48 hours after injection by digital large field gamma emrlera ('toshiba 901~). ?ol,al body scans (anterior and posterior views, matrix 128x512,speed - 10 c~ri/min) and regional planar irnaecs (maMx 256x256,600 Kent/view, zoom : 1.0) were acquired. Positive seao was observed in 6 of 7 pl,s with primary R&tS. No raise positive results were obl,ained in the 4 pal,ients with no clinical or radioloAieal evidence of disease. At 48Lh hr lower radioaclivil,y levels were observed in blood pool and in bone marrow in all patienl,s. In conclusions radioimlnunoseintigraphy is a sensil-ive and specific {eehniqne l,o detect untreated kbtS and seems l,o be also useful in tile follow u p of these patients.

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FP-3H2-1

Bares, K. H o r s t m a n n , C, A l t e h o e f e r , S.N. Reske, B. Mueller, R. O s i e k a , U. Buell Depts. of N u c l e a r a n d Internal- Medicine,. T e c h n i c a l U n i v e r s i t y of A a c h e n , G e r m a n y

Attard AR, Chappell MJ, Godfrey K, Dykes PW, Bradwell AR. IDRL, Medical School,University of Birmingham. Dept. of Engineering, UDiversity of Warwick, Coventry, U.K.

POSITRON EMISSION TOMOGRAPHY (PET) DEOXYGLUCOSE (FDG) FOR MONITORING RESPONSE IN MALIGNANT LYMPHOMA (ML)

MODEL BASED ~ T I O N S FOR EFFECTIVE CANCER RADIOIMMUNOTHF/gAPY. Ineffective radiation doses to tumour, due to low antibody uptake, remain a major limitation of tumour radioimmunotherapy. To identify which factors influence antibody uptake, we developed a compartmental model to simulate antibody distribution. This has been extended, in combination with MI~D dosimetry tables, to calculate integral tumour/body dose deposition for a range of antibody doses (i, i0 and 50mg), sizes (fragment iF] and whole molecule [W]) and affinities (Keq=10~-10 z~ M/L). Requirements for delivering 60 Gy to the tumour and a maximum body dose of 2 Gy, were initially calculated for I~I labelled antibody. The linear quadratic equation was then used to calculate the relative effectiveness of dose rates achieved with eaeh combination of antibody characteristics studied, a/S values for tumour and normal tissue were assumed to be i0 and 2.5 Gy respectively. Only, the following combinations achieved an effective body "radiation dose of less than 2 Gy. Ab Dose Keq Size Input Tumour (T) Body (B) T:B (rag) (M/L) Dose (MBq) Dose (Gy) Dose (Gy) 1 i0% 3 F 5574 55.7 1.42 39 1 I0 ~2 W 2047 59.9 0.68 88 1 I0 ~3 W 1340 59.9 0.44 136 i0 10 I= F 45293 38.5 1.22 31 I0 10 I~ F 13238 51.1 0.41 124 50 10 ~2 F 200505 37.4 1.60 23 50 1O I~ F 64889 49.9 0.66 75 In most cases the relative effectiveness of dose rates achieved with fragments was low. Results clearly show that in order to deliver an effective radiation dose to the tumour, with acceptable body levels of radiation, whole antibodies of the highest affinity are required.

R.

WITH F - 18 TREATMENT

A s s e s s m e n t of t h e r a p e u t i c e f f e c t s of r a d i o - a n d / o r c h e m o t h e r a p y in p a t l , e n t s w i t h ML is m a i n l y b a s e d on c h a n g e s of m o r p h o l o g i c a l t u m o r f e a t u r e s (size, d e n s i t y ) d e m o n s t r a t e d b y CT. It w a s t h e aim of o u r s t u d y to correlate CT-findings with metabolic tumor-data gained b y FDG-PET. V a l i d a t i o n w a s a c h i e v e d b y C T - g u i d e d b i o p s y . 32 P E T - s t u d i e s in 24 p t s . ( H o d g k i n ' s d i s e a s e n = l l , N o n - H o d g k i n L y m p h o m a n = 1 3 ) were p e r f o r m e d : 16 a f t e r c o m p l e t e d t h e r a p y , 16 in 8 p t s . b e f o r e a n d a f t e r t r e a t m e n t . All, p t s . w e r e i n v e s t i g a t e d in f a s t i n g s t a t e 3 0 - 9 0 min. a f t e r iv a d m i n i s t r a t i o n of 2 5 0 - 3 5 0 MBq FDG u s i n g a SIEMENS 9 5 3 / 1 5 P E T - S c a n n e r . A f t e r a t t e n u a t i o n c o r r e c t i o n F D G - u p t a k e in ML a n d b e n i g n t i s s u e s w a s q u a n t i f i e d b y ROIs u s i n g a n e x p e r i m e n t a l l y d e t e r m i n e d c a l i b r a t i o n f a c t o r to c o m p u t e %ID/ml, of t i s s u e . High FDG c o n c e n t r a t l , o n s , f o u n d in v i a b l e ML ( 3 . 7 - 1 ! . 2 E-03%ID /ml) c o m p a r e d to n e c r o t i c t i s s u e ( 0 . 6 - 2 . 1 E-03%ID/ml, p<.01), a l l o w e d a c c u r a t e t i s s u e c l a s s i f i c a t i o n b y PET in 3 0 / 3 2 s t u d i e s ( s e n s i t i v i t y 2 5 / 2 7 = 9 2 % , s p e c i f i c i t y 100%). In c o m p a r i s o n , CT y i e l d e d f a l s e n e g a t i v e r e s u l t s in 8/27 v i a b l e l y m p h o m a s (29%) a n d f a l s e p o s i t i v e r e s u l t s in 2 / 5 p t s . in c o m p l e t e r e m i s s i o n . We c o n c l u d e , t h a t FDG-PET is a h i g h l y r e l i a b l e m e t h o d to e v a l u a t e t i s s u e v i a b i l i t y of ML a n d m a y t h u s be g e n e r a l l y u s e d f o r m o n i t o r i n g of t r e a t m e n t r e s p o n s e in ML pts,

547

%~i~i~s!i¸¸'¸¸¸¸¸¸ gili!i!i!gi!iii!iiii

Tuesday, 3 September 1991

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FP-3H2-3

K.Wienhard, B.M. Mazoyer, H. Lundqvist, A.A. L a m m e r t s m a , G. Blomquist. Modelling Task Group on Tissue Heterogeneity, EEC

G.-J. Meyer, W. Burchert, K.F. Gratz, M.R. Gaab, E. Riekels, H. Dietz, and H. Hundeshagen, A b t e i l u n g Nuklearmedizin und spezielle Biophysik, A b t e i l u n g Neuroehlrurgie M e d i z i n i s e h e Hoehsehule Hannover, D-3000 Hannover 61, Germany

Concerted Action on PET Investigations of Cellular Regeneration and Degeneration. Effect of Tissue Heterogeneity Positron Emission Tomography.

on

Quantitation

in

Despite significant improvements, the spatial resolution of positron emission t o m o g r a p h y (PET) scanners will remain limited to a few millimetres. Consequently, the effects o f tissue heterogeneity on quantitation of physiological and biochemical parameters needs to be addressed, p a r t i c u l a r l y since the r e l a t i o n s h i p b e t w e e n these parameters and the recorded concentrations of radioactivity is often non-linear. The present study was carried out to provide a c o m p r e h e n s i v e overview o f the sensitivities of a variety o f currently used tracer procedures with respect to tissue heterogeneity. Simulation studies were p e r f o r m e d in w h i c h h e t e r o g e n e o u s tissue curves w e r e generated. Using the appropriate model operational equations, the parameters of these composite curves were calculated and compared to the average of the parameters of the individual tissue components. For brain, these components were grey and white matter, for heart, m y o c a r d i u m a n d spill-over signals from cavity and lung, and for tumours, regions with both high and low perfusion. Simulations were performed for tracer procedures used to measure blood flow, oxygen utilisation, glucose utilisation, amino acid uptake and a variety o f receptor studies. W h e r e appropriate, different implementations of the same tracer model were assessed. Sometimes these different implementations show quite a different degree of sensitivity to tissue heterogeneity. T h i s s t u d y s h o u l d , t h e r e f o r e , be h e l p f u l in s e l e c t i n g an implementation for a desired application. More importantly, it will be useful to better understand the various models in pathology.

QUANTITATIVE ANALYSIS AND COMPARISON OF GLUCOSE U T I L I Z A T I O N AND AMINO ACID TRANSPORT IN BRAIN TUMORS. It is she aim of this study to quantify the elevation of glucose utilization and amino acid transport in brain tumors. A valid approach for a quantitative comparison of physiological function under different conditions has been the determination of unidirectional transport constants and distribution volumes. Dynamic PET studies were obtained with a Siemens ECAT 951 system using 18-F FDG and ll-C-L-methionine in subsequent studies within 2.5 hrs. Arterialized blood samples were taken and analyzed for metaboiites in both studies. Glucose utilization was calculated with a customized program provided by the manufacturer on the basis of the Sokoloff model. Unidirectional methionine and glucose transport and their respective distribution volumes were calculated by the Gjedde-Patlak approach. Four grade Ill and five grade IV gliomas have been analyzed so far with this approach. The grades were verified postoperatively by histology. Average gray and white matter glucose utilization in all non-tumor regions (mostly contrelateral cortical) was 45 ±9 and 18 ± 4 ~LM/min/1O0g respectively, which is close to literature data. The grade III types showed a glucose utilization comparable to that of white matter in the tumor region, excluding necrotic tissue regions. The grade IV types including two recurrencies showed a glucose utilization slightly smaller than that of average grey matter. Unidirectional transport rates calculated by the Gjedde Patlak method showed the same pattern. The distribution volume of hanced by 50 % in grade III We currently investigate if diffusive influx contribution

the amino acid in tumors was enand up to 100% in grade IV systems. this increase can be attributed to from blood brain barrier damage.

In conclusion the dynamic and quantitative analysis of brain tumors with our mew high resolution scanner has corroborated our previously reported results, which indicate the superiority of amino acios for brain tumor diagnosis.

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FP-3H2-5

B. MAZII~RE, C. L O C ' H , J. D E L F O R G E , PH. H A N T R A Y E , M. K H A L I L I - V A R A S T E H , M. M A Z I E R E , Service Hospitalier Fr6d6ric Joliot, DRIPP-CEA, F-91401 O R S A Y Cedex, France.

Q, Muzik, R. Beanlands, G. Hutchins, T. Mangner, G. Wolpers, N. Ngnyen and M. Schwaiger. University of Michigan, Ann Arbor, MI.

C O M P A R T M E N T A L A N D E Q U I L I B R I U M ANALYSIS OF 7 6 B r - B R O M O L I S U R I D E B I N D I N G T O D O P A M I N E D2 R E C E P T O R S STUDIED IN B A B O O N BY PET.

COMPARISON OF N-13-AMONIA AND O-15-WATER TRACER KINETIC MODELS FOR QUANTITATION OF MYOCARDIAL PERFUSION USING DYNAMIC PET IN CANINE MODEL A 3 compartmental model has been recently developed at our laboratory for the quantification of myocardial blood flow (BF) by PET N-13 ammonia (AM) imaging. To determine the accuracy of PET flow measurements using this approach in comparison to those obtained with O-15 water (W) over a wide flow range, we compared PET flow estimates with radiolabeled microspheres (MS) BF in the closed chest model. 3-5 mCi of N-13 AM and O-15 W were injected intravenously as slow bolus (30s) following left atrial injection of MS at baseline and after infusion of dipyridamole (0.2-0.56 mg/kg). Dynamic PET imaging (PC 4600, TCC Corp) with high temporal resolution and arterial blood sampling was performed. Arterial blood was analyzed for N-t3 AM activity at 1,3,5,10 min after injection using a Sep Pac technique. Myocardial activity and plasma time-activity carves were fitted with a 3 compartmental model with (MC) and without (NC) blood metabolites correction. This model also includes terms describing the myocardial blood volume, which are used for correction of spillover and partial volume effect. A 2 compartmental model for O-15 W was employed and BF estimated using tracer tissue clearance rates. Myocardial BF determined by MS ranged from 53 to 620 ml/min/100g tissue. Both, O-15 W and N-13 AM PET flow was linearly related to MS flow.

76Br-Bromolisuride (76Br-BLIS) is a radiolabelled d o p a m i n e r g i c antagonist used in clinics for the visualization of D2 receptors. In vivo quantification of 76Br-BLIS striatal binding parameters has been p e r f o r m e d in vivo in b a b o o n by PET using kinetic a n d equilibrium models. The saturation model determined under different conditions of receptor o c c u p a n c y (variation of injected mass of BLIS) provides measurements of receptor density (Bmax = 49 _ 2 pmol/g) and receptor affinity (Kd = 1.7 + .3 riM). In this model, data f i o m preliminary ex vivo measurements have been used to determine the value of the fi'ee fractions. The non equilibrium non linear kinetic model used is a classical four c o m p a r t m e n t s model. For the identification of its seven parameters, the experimental protocol included three successive injections of 76Br-BLIS coadministered with increasing doses of cold BLIS. Thus, concentration of available receptor sites (Bmax = 73 _+ I 1 pmol/g), association, dissociation a n d affinity constants (Kd = 1.9 _+.9 riM) could be evaluated. These in vivo data are then c o m p a r e d with the 76Br-BLIS in vitro binding parameters measured in baboon striatal m e m b r a n e h o m o g e n a t e s . The various results obtained using these models allow to validate the use of the striatum to cerebellum radioactive concentration ratio as an index of specific binding in clinical situations.

548

O-15 N-13 AM (NC) N-13 AM (MC) N-13 AM (VD fixed)

y = 0.944 x y = 0.706 x y = 0.685 x y = 1.006 x

(R = 0.86) (R = 0.87) (R = 0.87) (R = 0.86)

(N = (N = (N = (N =

15) 15) 15) 15)

At high flows, the N-13 AM blood flow estimates became unreliable due to difficulties in separating the shape of the arterial blood curve from the rapid washout component of the myocardial tissue. Constraining each fit by forcing a constant Kl:k2 ratio (VD fixed) produced flow estimates consistent with MS flows. Thus, N-t3 AM allows quantification of flow over a wide flow range with similar accuracy as O-15 W, but without the need of blood activity correction and improved image quality. Correction for N-13 AM metabolites does not appear neccessary, however restriction of the tracer tissue VD is neccessary to maintain a linear response at high flow states.

Tuesday, 3 September 1991

FP-3H2-6

FP-312-1

L N y i t r a i , H.Herzog, E.Rota Kops, R.SeitzL P . K l i n k h a m m e r , F.Jtilicher and L.E.Feinendegen. I n s t i t u t e of Medicine, R e s e a r c h C e n t r e Jfilich, Jfitlch, a n d 1) D e p a r t m e n t of N e u r o l o g y , Univ. Dtisseldorf, FRG

Y Choi, R A Hawkins, C Messa, C K Hoh, M Dahlbom, SC H u a n g , l Barrio, N Satyamurthy, F Singer, J Adams, I Salusky, A Nissenson, W Goodman, C Schiepers, ME Phelps. U C L A School o f Medicine, Los Angeles, CA.,

TRUE INPUT CURVE GENERATION FOR BRAIN PERFUSION EVALUATION IN Hzl~O a n d isO-BUTANOL POSITRON EMISSION TOMOGRAPHY (PET) STUDIES. Our aim w a s to d e v e l o p a m o d e l - i n d e p e n d e n t n u m e r i c a l method which takes into account the dispersion effects of t h e m e a s u r e d i n p u t c u r v e s fit) u s e d f o r t h e c a l c u l a t i o n of p a r a m e t r i c i m a g e s of c e r e b r a l p e r f u s i o n (CBF). For the dispersion correction Bronikowski's idea for the c o m p u t a t i o n of a " m o d e l - f r e e t r a n s f e r f u n c t i o n " w a s used. The correction was governed by the equation: 1 / a l p h a x f _ c o r ( t ' ) = f ( t ) , w h e r e t ' = a l p h a x t a n d f cor is t h e c o r r e c t e d i n p u t c u r v e . To v a l i d a t e t h e m e t h o d , f i r s t - p a s s d y n a m i c g a m m a c a m e r a s t u d i e s (dGCS) w e r e c a r r i e d o u t in p a t i e n t s a n d time a c t i v i t y c u r v e s (TACs) w e r e g e n e r a t e d o v e r d i f f e r e n t r e g i o n s p l a c e d on t h e r o u t e of t h e c i r c u l a t i o n . The m e t h o d w a s u s e d to t r a n s f o r m one TAC I n t o a n o t h e r . It w a s f o u n d , t h a t e v e n in e x t r e m e c a s e s ( b r a i n TAC r e f e r r e d to l u n g TAC) t h e b r a i n c u r v e ( t h e r e c i r c u l a t i o n part was omitted) was transformable into the lung curve. In dGCS t h e a l l o w e d r a n g e of a l p h a w a s e s t i m a t e d ( a l p h a = 0 . 6 - 1 . O ) . In H=t~O b r a i n p e r f u s i o n a t u d i e s , t h e n u m e r i c a l m e t h o d w a s s u c c e s s f u l l y a p p l i e d on r e a l i n p u t TACs o b t a i n e d w i t h a n a u t o m a t i c blood s a m p l e r i n t e r f a c e d to a PET s c a n n e r (SCANDITRONIX PC4096 15-WB). Using a l e a s t s q u a r e f i t t i n g p r o c e d u r e for c a l c u l a t i o n of CBF, t h e e r r o r f u n c t i o n w a s r e d u c e d b y 50% a t t h e o p t i m u m a l p h a v a l u e (=0.9). B e c a u s e t h i s n u m e r i c a l m e t h o d is e a s y to p e r f o r m a n d d o e s n o t r e q u i r e a p r i o r i k n o w l e d g e a b o u t t h e t y p e of t r a n s f e r f u n c t i o n , i t is well s u i t e d to be i n c l u d e d in t h e f i t t i n g p r o c e d u r e to c a l c u l a t e t h e CBF in PET s t u d i e s .

QUANTIFICATION OF BONE METABOLIC RATE WITH F-18 FLUORIDE ION AND DYNAMIC PET Fluoride ion exchanges with hydroxyl groups in the hydroxyapetite crystal of bone. In order to determine a bone metabolic index, kinetics o f bone uptake a n d p l a s m a clearance o f F-18 Fluoride ion were evaluated in normal volunteers and patients with focal bone disease with a whole b o d y P E T device (Siemens 931-08) . I m a g e s were reconstructed with a Shepp L o g a n 0.15 filter after photon attenuation correction using an external-source trasmission scan. Subjects were injected with 5-10 mCi F-18 ion intravenously, and i m a g e d with a dynamic sequence of images over a 1 hour period. Arterialized plasma samples and whole blood samples were obtained from a heated vein. A three compartment model was applied to the dynamic data, using an input function directly acquired from imaged left ventricular blood pool and from arterialized plasma samples. Parameters generated included kl and k2 (forward and reverse transport from plasma to an unbound bone compartment) and k3 and k4 (incorporation and release from a bound bone compartment). The macroparameter K (=Ktk3/(k2+k3), indicative o f net incorporation of F-18 into the bound compartment in bone, was determined f r o m individually estimated microparameters using non linear regression, or from a Patlak graphical method (k4 is very small). The K values estimated by graphical analysis correlated with K values estimated by non linear regression (r --- 0.99, slope = 1.05). The average vertebral K value in 11 normals w a s 3.43_+0.41 ml/min/100g. Patients with focal bone disease (cancer o~ c o m p r e s s i o n fracture), had higher p e a k K values (up to a 5 fold increase f r o m normal values). Parametric images of K generated in cross section improved image detail by suppressing the signal from vascular activity. This also facilitated quantification of K in specific bone regions. K values increased in patients with focal bone disease, indicating this technique is potentially useful for n u m e r i c a l l y evaluating chances in bone metabolism in disease states.

FP-312-2

FP-312-3

~ ,

M. l-'.i tap~:z, ~;.Erben~i, M. 0nlfi.. G ciagiu, T. G~iip, C.F. B-ekdik. Departments of Nuclear Medicine and Orthopedics, B,acettepe University. 06100, Ankara, ~l~rkiye

Bengiil GONALP, Btilent ERCENK, Hikmet BAYHAN. Ethem GUR, Emel ¢)ZTORK, Cumali AKTOLUN Department of Nuclear Medicine and Orthopedy Giilhane Military Medical Academy and Faculty Ankara/TURKEY

99mTc-MIBI ~fPTAKE OF BENIGN A}FD IL~LIGI.IANT B O ~ LESIONS: A COMPARISON WITH 99f.Tc-MDP

ROLE OF BONE SCANNING IN THE MANAGEMENT OF NON-UNITED FRACTURES: A Clinical Study

The potential of MIBI in bone tumor imaging were assessed in 45 pts with histopathologically proven bone pathologies[J9 benign(B), 26 maligr~nt(M)], in comparison to 99rnTc-1~P bone scan. Static images were obtained 1 h after the I.V. injection of MIBI (370 MBq).72 h following_ MIBT study, lff)P bone scan was performed. Four pts with M bone t~mor were st~aied both pre- and post-chemotherapy. The degree of MIB! uptake was classified into 4 levels taking the heart as a reference. 0=ba ckg r our~5, l=mild activity, 2=activity equals to heart, 3=activity greater than heart. Sensitivity MIBI Uptake level (n=) __.(~_;:__ o l 2 3 Malignant 25/26(96%) i* 7 11 7 Benign 10/19(52.6%) 9** i0.** 0 O *tmdifferentlated adeno-ca metastasis to the sterntm. **n=5 recent bone fracture, n=2 osteochondroma, n=i exostosis, n=i osteoid asteoma. ***n=7 osteomyelitis, n=l osteochordroma, n=l fibrous dysplasia, n=l cailotasis for tibial nontuaion. All lesions P~d increased uptake on MDP images without any prominent difference between B and M, while MIBI uptake in the M lesions was more strikir~. than seen in benign cotmterparts. 3/4 pts with metastatic lung lesions ar~ 2/2 pts with metastatic lymph nodes were clearly demonstrated by MIBI, but not by t~P. There ~:ras no correlation between differentiation of tumor and MIBI uptake level. MIB$ uptake was ir~ibi,ted by chemotherapy ai~4 it was superior to I~P in e~.~.lue.ting response to chemotherapy.

99m Tc MDP bone imaging was performed in 45 patients with non-united fractures with a median time of 8 months since injury. The aim of this study was to predict healing response of non-united fractures to electrical stimulation treatment using pulsing electromagnetic fields (PEMFES). Three spesific bone scan paUerns were identified. (TABLE 1). The first and most frequent pattern was intense, uniform, increased uptake at the nonunion site (Group 1). The second pattern revealed an area of decreased activity surrounded by increased uptake on both side (Group 2). The third pattern was indeterminant; the presence of a cold area could not be judged with certainty. TABLE 1: Tc-99m/vlDP Uptake Pattern in Nonunion i n 45 Patients. Bone Scan Pattern: Number of % of patients patients Intense uniform uptake 24 53.3 Photon deficient area 14 31. l Indeterminate panern 7 15.5 All patients underwent PEMFES treatment. Response to PEMFES was shown in TABLE 2. TABLE 2: Relationship Between Scan Pattern and Success of Treatment of Nonunion with PEMFES No of % Group Patients Healed Failed Success 1 24 21 3 87.5 % 2 14 0 14 0% 3 7 3 4 42.8 % Total 4~ 24 21 ~,~ % In Group 1, of the 3 patients who failed to heal, 2 were attributed to inproper immobilization, and one was subsequently shown to have osteomyelitis. None of the patients in Group 2 had evidence of healing, and all of these patients underwent surgical exploration. Four patients had pseudoarthrosis, 3 had a soft tissue interposition, 3 had occult osteomyelitis, and 4 had a fracture gap more than five milimeters. In Group 3, the failures were attributed to inadequate immobilization and the presence of occult osteomyelitis. We concluded that in nonunion fractures a bone scan is a useful tool for the proper selection of patients for surgery or PEMFES treatment.

549

Tuesday, 3 September 1991

FP-312-4

FP-312-5

J.Hierholzer, G.Schwetlick*, G.Barzen, A.Debrand-Passard, M.Cordes**, H.Henkes, R.Langer, R.Felix Dpt. Radiology, Institut fiJr Diagnostikforschung**, UKRV-C, Dpt. Orthopedic Surgery*, OHH, Freie Universit~it Berlin

L. Kostakoglu, H. Abdel-Dayem, C. Caluser, S.D.J.Yeh, S.M. Larson. M e m o r i a l S l o a n - K e t t e r i n g Cancer Center. New York, NY, 10021.

BONE-SPECT AND 3D-RECONSTRUCTION IN PATIENTS WITH HIP-HEAD-NECROSIS BEFORE AND AFTER IMPLANTATION OF A PEDICLED PELVIC BONE G R A F t Plain bone scintigraphy, bone-SPECT with axial and 3-dimensional reconstruction was evaluated for its diagnostic value in the follow-up of patients with hip-head necrosis after implantation of a pedicled pelvic bone graft. Ten patients with hip head necrosis were e x a m i n e d pre- and postoperatively performing Tc99m-DPD-SPECT to evaluate the viability of the hip head before and after treatment with a pedicled pelvic bone graft. One week before, three weeks, 3 month and 7 month after surgery clinical features were compared with the results of conventional X-ray-examinations and scintillation-studies. Scintigraphy was performed with 650 MBq Tc))m-DPD in a cine-phase study ( perfusion 0-120 sec p.i., blood pool imaging 5 min p.i., static images 3 h p.i.). SPECT images were acquired 3.5 h p.i., a 3d-reconstruction of the hip was performed in alI cases. Evaluation was visually and quantitatively in ROI-technique. In all patients an increased local perfusion as well as an increased regional osseous metabolic activity of the hip head could be visualized after the operation. The highest local bone metabolism has been found in the affected hip head three weeks after surgery and lowest 7 month thereafter. In detecting the extend of osseous hypermetabolism the reconstruction of axial slices of SPECT-data clearly proofed to be superior to planar views. In the postoperative follow-up of patients with hip head necrosis treated with a pedicled pelvic bone graft only SPECT and planar scintigraphy allow reliable quantitative analysis of the regional metabolism of the bone. By the ROI-technique changes of the viability of the revitalized hip head can be detected and may announce em'ly complications such as necrosis. SPECT images are superior to planar images in evaluating the hip head. 3-D-display simplifies image interpretation and topographic information.

CORRELATION OF THALLIUM-201 CT/MRI/ANGIOGRAPHY WITH HISTOLOGIC FINDINGS IN BONE AND SOFT TISSUE SARCOMAS . It is of g r e a t i m p o r t a n c e to d i f f e r e n t i a t e local tumor (tin) r e c u r r e n c e f r o m b e n i g n l e s i o n s i n p a t i e n t s (pts) w i t h bone a n d soft tissue sarcomas, s p e c i f i c a l l y f o l l o w i n g chemo/radiotherapy. We c o r r e l a t e d TI-201 c h l o r i d e i m a g i n g , MRI (9), CT (4) or a n g i o g r a m s (3) w i t h b i o p s y r e s u l t s in p r e v i o u s l y treated 16 pts w i t h bone and soft tissue sarcomas. All pts u n d e r w e n t TI-201 i m a g i n g 20 rain. f o l l o w i n g the i n j e c t i o n of 3 mCi of TI-201 chloride. The total n u m b e r of c o u n t s and pixels in r e g i o n s of h i g h e s t TI-201 u p t a k e at the t u m o r site and the c o n t r a l a t e r a l site w e r e obtained. The r a t i o b e t w e e n c o u n t s / p i x e l s o v e r the r e g i o n of t u m o r and c o n t r a l a t e r a l site was calculated, All TI-201 s c a n s w e r e in complete a g r e e m e n t w i t h biopsy results, T h e r e w e r e l l t r u e positive TI-201 s c a n s w i t h r e c u r r e n t m a l i g n a n t tumor. Of these, M R I / C T / A n g i o g r a m s was t r u e positive in 7 and e q u i v o c a l i n 4 cases. In these e q u i v o c a l cases i n f l a m m a t o r y p r o c e s s o r f i b r o s i s could not be d i s c e r n e d f r o m r e c u r r e n t tumor. TI-201 w a s true n e g a t i v e in the r e m a i n i n g 5 p a t i e n t s , w h e r e a s CT/MRI/Angiograms was t r u e n e g a t i v e o n l y in 3 and false positive in 2 patients. The a v e r a g e ratio b e t w e e n c o u n t s / p i x e l w i t h i n the t u m o r and c o n t r a l a t e r a l site was 3.2 *__1.1. In all t r u e n e g a t i v e cases the ratio was below 1.4. We conclude t h a t TI-201 c h l o r i d e i m a g i n g is m o r e r e l i a b l e t h a n o t h e r i m a g i n g m o d a l i t i e s s u c h as MRI/CT or a n g i o g r a m s for p r e d i c t i n g r e c u r r e n c e in p r e v i o u s l y treated pts w i t h bone and soft tissue sarcomas.

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LF Verheij (1), JAK Blokland (1), SE Papapoulos (1), AH Zwinderman (2), EKJ Pauwels (1). Department of Nuclear Medicine, University Hospital (1) and Department of Medical Statistics, State University (2), Leiden, the Netherlands.

F. De Geeter, A. Bossuyt, M. Verhas, G. Morgan, J.R.Thornback. AZVUB and Brugmann Hospitals, Brussels and Medgenix, Fleurus, Belgium.

HOW TO MONITOR BONE MINERAL CHANGES. In bone densitometry, the optimum approach for the monitoring of bone mass changes in patients is studied. We have developed two models. One to examine the effect of various data acquisition set ups on the length of a confidence interval; and a second to compute the scan time interval and number of measurements that are required to detect fast losers ( > 3 % per year), given a coefficient of variation (CV) of 1.1% (which is the registered in vivo precision of Dual Energy X-ray Absorptiometry instruments). It appeared that the effect of additional measurements on the length of a confidence interval depends on the relative moment of the extra observations. For instance, four equidistant measurements result in a reduction of the interval from 2.77 % to 2.63 % (using a CV of 1% and a 95 % confidence interval), whereas two pairs of duplicate measurements at the ends of the period yield an uncertainty range of 1.96%. From a patient management point of view, a scan time interval must be chosen so that the expected change in bone mineral density will be significantly detectable. Also, it is preferred to detect fast losers within reasonable time. We found that a nine month period is required to be able to detect fast losers, if a CV of 1.1%, duplicate measurements, and a 95 % significance level are applied. As a number of assumptions have been used, the confidence intervals and proposed scan time interval are minimum values. These values can only be achieved in a carefully controlled research environment. We conclude that for the detection of bone loss an increase of the number of measurements per patient visit is more effective than increasing the number of visits. We propose duplicate measurements and a scan time interval of nine months for the follow-up of osteoporotic patients.

COMPARISON OF Tc-99m-MRP20 AND Tc-99m-HMPAO AS SPECT BRAIN IMAGING AGENTS.

550

Tc-99m-MRP20 belongs to a new class of brain perfusion agents. In order to provide evidence of the efficacy of Tc-99m-MRP 20 for the qualitative assessment of regional cerebral blood flow by means of SPECT in pathological conditions we conducted a Phase II clinical trial in 30 patients with an entry diagnosis of either stroke (20 pts), dementia (Tpts) or tumor (3pts). To this purpose we compared the brain distribution of Tc-99mMRP20 with that of Tc-99m-HMPAO in SPECT studies performed within 72 hrs of each other. Following injection of 20 mCi of each tracer, data acquisition, reconstruction parameters and image display were kept the same for both studies and identically reorientated transverse slices were independently evaluated by 2 observers. No major discrepancies in the regional distribution were observed between the two tracers except for a glioblastoma patient, who showed a positive Tc-99m-HMPAO uptake in contrast to a hypoactive lesion with Tc-99m-MRP20. In 10/30 pts both observers preferred interpreting the Tc99m-HMPAO images. However, with respect to lesion identification, the Tc-99m-MRP20 studies showed a larger (4/30) or more (5/30) perfusion defects than did the Tc-99m-HMPAO studies. No adverse effects to the administration of Tc-99m-MRP20 were seen and safety studies did not yield changes of any significance in the parameters studied. Although in general the brain uptake of Tc-99m-MRP20 shows a good correlation with that of Tc-99m-HMPAO the findings in the glioblastoma patient give rise to the assumption that after passage across the blood brain barrier, both these tracers may have a different retention mechanism in the brain.

Tuesday, 3 September 1991

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A. Bockisch, Ch. Elger, A. Hotze, F. Griinwald, G. Hefner, E. Klein, H.J. Biersack. Kliniken far Nuklearmedizin und Epileptologie, Universit~iten Bonn & Mainz, Germany

W. R e i c h e , U. Buell, Ch. Isensee*, C. Weiller*, H.J. Kaiser, C. Altehoefer) E. B. Ringelstein*. Depts. of Nuclear Medicine and Neurology, Technical University (RWTB) Aachen, FRG

PRESURGICAL EPILEPTIC DIAGNOSIS -

COMPARISON OF HMPAO-SPECT-, 18FDG-PET AND MRI-FINDINGS IN PATIENTS WITH CEREBRAL MICROANGIOPATHY (MA)

A COMPARISON OF MAGNETIC RESONANCE

TOMOGRAPHY (MRI) WITH HMPAO-SPECT. MRI and HMPAO-SPECT studies were performed to detect possible sites of seizures with the temporal being of special interest. Patients and methods: 114 pts were investigated so far: 12 connatal or early childhood changes, 18 tumors (12 malign.), 17 other benign changes, 10 psychogenic/psychiatric-inducedseizures. In 67 the origin of the disease was unknown. MRI (Philips Gyroscan, 1.5 T) standard sequences: 8 mm transversal slices proton- and T2weighted (SE 3000/20/90); 5 mm coronal and 4 mm transvers. T1weighted native and after Gd-DTPA (SE 650/17). The volume of the temporal horns and the relative signal intensities in the hypocampus/amygdala were determined quantitatively. SPECT (Picker double head) acquisition (360 °, 60 views) started 10 to 60 rain after the application of 740 MBq Tc-99m-HMPAO. The results were compared with histopathology, postsurgical clinical course, cCT, and angiography. Results: So far final results are available for 60 p~itients. HMPAO scans and MRI agreed with respect to the localization (both pos. or neg.) in 40 pts. In others only MRI was positive in 10, only HMPAO in 4 and none in 6 pts. Dynamic studies with contrast media were of no help. Relative dilatation of the temporal horn is only weakly correlated with the affected side. There were no striking signal differences in the hypocampus/ amygdala region. Conclusions: MRI is a valuable procedure in the presurgical diagnosis of seizures. Lesions on the mm-scale may be detected. HMPAO-SPECT may identify perfusion disturbance without morphological changes. Thus both methods should be used complementary.

MA-patterns are lacunar infarctions and periventrieular low density in CT, rCBF-reduction in periventricular matter (PM) in SPECT. In this study rCBF (400 MBq 99mTc-HMPAO, Rota-Dual) and cerebral glucose metabolism (rCGM) (350 MBq ISFDG, ECAT 533/15 PET) in 17 pts. (9 male, 8 female, age 70,2 ± 7,8 year) and in 7 controls were correlated with MRI-findings. PM- and parietal cortex (PC)ROl's were evaluated in SPECT semiquantitatJvly in relation to a cerehellum-ROl and in PET quantitativly as nCi/ml. Results: slight MA ~I single PM DWML PC minor atrophy n 7 SPh~'~Tin cpm/pix normalized

severe MA multiple to confluent DWML severe atrophy i0 to cerebellum

control normal normal 8

PM 0.71 ±0.06 $ 0.65 ±0.04 * 0.76 ±0.11 PC 0.83 ±0.04 § 0.78 ±0:06 § 0.84 ±0.0 PET in nCi/ml norm. to i n j . a c t i v i t y + body s u r f a c e PM 49.8 ±2.7 * 37.6 ±3.7 * 52.6 ±3.1 PC 89.7 ±6.8 * 71.3 23.6 * 96.3 ±4.7 DWML: "deep white matter l e s i o n " s p = 0.029, * p < 0.025, § not significant SPECT revealed in severe MA a rCBF-reduction in PM, however not in PC. rCGM was reduced both in PM and less pronounced in PC. This correlated morphologically (MRI) with a cortical atrophy.

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J . L ~ v e i l l ~ , MI.Botez, J. V4zina, R.Lambert, R . T a i l l e f e r , B.Lefebvre. Nuclear Medicine, Neurology and Radiology, H6tel-Dieu de Montr4al, Quebec, Canada, H2W IT8.

D. L. Munz, R. Verheggen, J. Jansen, A. Helwig, D. Sandrock. Departments of Nuclear Medicine, Neurosurgery, and Neuroradiology, Georg August University, G6ttingen, Germany.

HMPAOTc99m SPECT EVALUATION OF CEREBELLAR DISEASES: RELATIONSHIP WITH CLINICAL AND CT-SCAN FINDINGS. The aim of the present study was to determine with SPECT the pattern of Tc99m HMPAO d i s t r i b u t i o n in cerebral and c e r e b e l l a r tissue of patients with primary cer e b e l l a r involvement. METHOD: Four groups were studied, l) F r e i d r e i c b ' s ataxia (FA), 2) Olivo ponto cereb e l l a r atrophy (OPCA), 3) c e r e b e l l a r i n f a r c t (DI), 4) pair-matched normal controls f o r age," sex, education (N). Regions of i n t e r e s t (ROIs) were compared with Ct-scan data and c l i n i c a l findings. DISEASE GROUP NUMBER SEX AGE T - 7 --7 F-l ,-8-~--M-16 19~-9 OPCA II 30 F-20, M-lO 39-72 CI Ill lO F-lO, M-lO 42-79 N IV 30 F-15, M - 1 5 20-70 RESULTS: OPCA and FA patients showed reduced cerebell a r hemisphere and vermis uptake which is more important than expected from atrophy observed on Ct-scan. This degree of uptake c o r r e l a t e s well with o v e r a l l c l i nical s e v e r i t y and neuropsychological disturbances. Reduced uptake in basal ganglia and f r o n t a l cortex was more important f o r OPCA than FA which c o r r e l a t e s with Ct-scan atrophic f i n d i n g s . Primary u n i l a t e r a l cerebell a r i n f a r c t had c o n t r a l a t e r a l c o r t i c a l reduced uptake mainly in p a r i e t a l cortex suggesting a reverse diaschisis. CONCLUSION: HMPAOc e r e b e l l a r uptake could serve as an i n d i c a t o r of s e v e r i t y of these diseases. The cer e b e l l a r i n f a r c t c o n t r a l a t e r a l cortex involvement could be r e l a t e d to cerebello c o r t i c a l loops disturbances and represents a reverse diaschisis.

R A D I O I M M U N O D E T E C T I O N OF INTRACRANIAL A Tc-99m ANTIGRANULOCYTE ANTIBODY: STUDY.

ABSCESS USING A PROSPECTIVE

Symptomatic intracranial abscess presents a serious posttraumatic, postinfectious, or postoperative complication requiring surgical revision. The ring structure depicted on CAT or M R T scan is unspecigic. Hence, it was the aim of this p r o s p e c t i v e study to test the diagnostic usefulness of a Tc-99m a n t i g r a n u l o c y t e antibody in the early d i f f e r e n t i a t i o n of the etiology of the ring structure. In 18 patients (pts) (ii males, 7 females, age 29 79 years) with suspected intracranial infection but equivocal clinical symptoms, planar scans of the whole b o d y a n d SPECT scans of the head w e r e taken 4 - 7 hr after i.v. injection of 555 - 740 M B q Tc-99m a n t i g r a n u l o c y t e antibody BW 250/183. The pts had antibiotic, ant±mycotic, or corticosteroid .therapy. The diagnosis was c o n f i r m e d by surgery (14 pts) or clinical follow s up. The immunoscan was true positive (abscess) in 6 pts and true negative (brain tumour) in 9 pts. There was no false negative but 3 false positive (i fresh tumour bleeding, 2 sarcomas within glioblastomas demonstrating bulky per±vascular granulocytic infiltrates) immunoscintigraphic findings. There was no obvious detrimental effect of antibiotic, ant±mycotic, or corticosteroid therapy. In conlusion, in spite of a few false positive results, the T c - 9 9 m a n t i g r a n u l o c y t e antibody is a useful tool in the early d i f f e r e n t i a t i o n between intracranial abscess and tumour as well as in the d e c i s i o n not to p e r f o r m operative revision.

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Tuesday, 3 September 1991

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~ASSINA A~ RUBELLO D, CASARA D.

Elmaleh D.R.. Brownell A-L, Isacson O'., Schumacher J., Madras N', Brownell G.L Massachusetts General Hospital, Boston, MA, "McLean Hospital, Belmont, MA, " New England Regional Primate Center, Soutborough, MA.

Radiotherapy and Nuclear Medicine Department, pathology Department, University and General Hospital of Padua, Italy. THYROID CANCER (TC) IN PEDIATNIC AGE ~C is an uncommon observation in pediatric age without de finitive diagnostic and therapeutic approach. In the pr~ sent study we investigated the survival and prognostic factors of 37 pts aged 15 yrs, These cases were obtain~ ed out of our whole series of 1457 pts with TC in the period 1987-87. 27 were female and I0 male pts, F:N=2.4, F: ratio was 1 for pts aged 12 yrs. Histology was Papillary (P) in 31, Follicular (F) in 4, Medullary in 2 cases. P:F r a t i o w a s 7.7 while it was 2.S in whole series. Considering pts with differentiated TC, ]S eases (ell P) had distant metastases (DM) (S6%), 8 to lung, 5 to media~ tinum, i0 pts presented with lymphnode N (LNM). In whole series DN were present in 14% of cases: of these, S4% we re in the bones, while in the pediatric group no hone N were ohserved. LNN were present in 47% of adult series vs 29% of the pediatric group. Local extrathyroida] inva sion had the same percentage in the two groups,16 vs 14%. Our pts were treated by total thyroidectomy and SS/S5 by ]SlI therapy. After a 8 yr_ mean follow-up all Dta were living, 73% disease-free, 34% with disease. In conclusion; i. in pediatric age thyroid nodules need careful attention, since TC hears an aggressive behaviour in this age group; 2. M are early and frequent, to lungs and LN, but not to bones with a good response to ISII therapy; 3. total thyroidectomy and iSlI therapy are recommended as elective treatment for these pts.

N-[C-11]-METHYL-2B-CARBOMETHOXY-3B-Pt{ENYL TROPANE ([C-11]PT) AND GLUCOSE UTILIZATION IN A PRIMATE MODEL OF HUNTINGTON'S DISEASE. To characterize changes in presynaptic dopamine receptors and glucose utilization in a primate model of Huntington's disease we carried out PET-studies using [C-11]PT and [F-18]fluoro-deoxy-D-glucose (2FDG) prior to mad after introducing a small unilateral lesion by injection of the glutamate receptor agonist quinolinate into the caudate-putamen of the Cynomolgus monkey. Imaging was performed using a high resolution positron emission tomograph (PCR-I) with a spatial resolution of 4.5 mm. After I.V. injection with 5 mCi of [Cll]PT, brain activity was followed for 60 min. The caudateputamen region showed high uptake for the compound. The ratio of caudate putamen to cerebellum was 2.3+/- 0.2 at 30 rain. After the receptor study a quantitative study of gIucose utilization was carried out using 2FDG. Six weeks after the injection of quinolinate into the right caudate putamen, imaging studies were repeated. Glucose utilization was decreased 10-20 % in the affected tissue areas while no difference was observable in dopamine binding sites using [C-11]PT. Our preliminary studies support the use of the primate model of Huntington's disease to monitor in vivo functional changes.

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Sautter-Bihl Marie-Luise, *Rau Gabi, Heinze H G , *Bihl H:

S. Lastoria, L. Maurelli, C. Carae6, E. Vergara, L. Castelli, M.T. di Tullio*, F. Casale*, P. Indolfi*,M. Salvatore. Nucl. Med. Dept. University of Napoli 2nd Medical School,*Pediatric Branch ist Med. School, Napoli

Dept. of Radiooncology and Nuclear Medicine Karlsruhe, *Katharinenhospital Stuttgart, FRG CHANGE IN MIBG-UPTAKE DURING RETINOIC ACID [RA) - INDUCED DIFFERENTIATION OF HUMAN NEUROBLASTOMA CELLS I N VITRO. Metaiodobenzylguanidine [MIBGI has been proven successful in imaging neuroblastoma [NBLI. As NBLs tend to differentiate to minor malignant counterparts, both spontaneously or during therapy, the question arises, whether or not, and if so, to what extent this cellular change is paralelled by a change in MIBG-uptake. The answer to this question may be essential for the assessment of the value of MIBG-scintigraphy in NBL management. The aim of this study i s t o document quantitatively the possible change, if any, of MIBG-uptake in an in v i t r o NBL cell line model. We used the human NBL cell line SK-N-SH, which is known to concentrate MIBG, and RA, which induces a variety of differentiated functions, including phenotypic differentiation. A MIBG-uptake assay wasestablished to assess quantitatively the MIBG-uptake in an in v i t r o cell line environnernent. The NBL cell line SK-N-SH was continuously exposed to 5 pM all-trans RA for 8 days. Most of the SK-N-SH cells showed a marked increase in neurite extension during RA-induced differentiation. The MIBG-uptake droped down to 57 % of the uptake of control SK-N-SH cells w i t h o u t RA pretreatment. These data show that: (I) RA is a suitable agent to induce differentiation in SK-N-SH, (2) RA-induced differentiation of SK-N-SH is followed by a marked decrease in MIBGuptake, (3] Extending I and 2 to clinical situations: MIBGtherapy should be applied preferentially tO not yet differentiated NBLs, i.e. earlier than in current therapeutic protocols.

552

1-131 MIBG SCINTIGRAPHY IN THE LOCALIZATION AND FOLLOWUP OF NEUROBLASTOMA: COMPARISON WITH OTHER TECHNIQUES. In 56 pts with neuroblastoma (NB, n°=40)and ganglioneuroblastoma (GNB, n°=13) and other pediatric tumors (n°=3) 1-131-MIBG scan (0.5 mCi iv, images at 24,48, and 72 hr) was compared with CT, bone scans, US and MRI. The pts were divided in 2 groups: Group 1 (49 pts) was evaluated before treatment with subsequent histological die gnosis of NB and GNB; Group 2 (37 pts) was studied after surgery and/or chemotherapy (30 pts were in follow-up from Group I) for a total of 114 scans. Results: Group 1 Group 2 TP TN FP FN TP TN FP FN MIBG 38 2 0 9 30 5 0 2 CT 46 0 0 3 29 3 2 3 Other 37 2 4 3 32 5 0 0 (TP= true positive P, TN= true negative N, FP= false P, FN= false N); CT was the most sensitive 93% in Group 1 vs. 81% of MIBG, the specificity was 100% for both CT and MIBG, 33% for other combined modalities. In Group 2 MIBG (93Z) and CT (90%) were comparable for the sensit ! vity; while the specificity was 100% for MIBG and 60% for CT. The accuracy was 94% for MIBG and 86% for CT in Group 2. A total of 162 lesions was demonstrated using all combined modalities, among these 31 were unsuspected before the MIBG scintigraphy. These results lead to the following conclusions: a) before the surgery CT as well as other radiographic methods are more accurate, postsurgery MIBG is the most accurate; b) bone-marrow metastases can be easily imaged better than other methods.

Tuesday, 3 September 1991

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J.R Zhu, J.D. Lund~roso. 0. Hartmann, Y. Rabarison, J. Lemerle and C. Parmentier. Institut Gustave Rcussy and U66 INSERM F- 94805 Villejuif i France

B.L. Shulkin, B.Shapiro, R.J. Hutchinson, J.C. Sisson, S. Mallette, E.E. Mudgett. University of Michigan Mott Children's Hospital, Ann Arbor, Michigan, U.S.A.

123I-mIBG SCANS IN UNTREATED NEUROBLASTOMAS: A STUDY OF 109 NEWLY DIAGNOSED CHILDREN We re-evaluated the sensitivty (SE) and the specificity (SP) of meta-iodobenzylguanidine (mIeG) scans in neuroblastoma at the time of diagnosis, avoiding any interference with therapy. A total of 109 children aged from 2 months to 13 years had, before receiving any therapy or surgery, whole body scans performed 24 hours after injection of 123I-mIBG at the posology of 3.7 MBq /kg (the specific activity was 185 MBq per mg of mIBG). Within a short delay, non scintigraphic modalities gave the following results: a neuroblastoma was present in 81 cases and a ganglioneureblastoma in 28 cases; the stage of the disease was I in 2 cases, II in i0, III in 23, IV in 67 and IVs in 7 cases; the site of the primary tumour was the neck or thorax in 20 cases, the abdomen or pelvis in 81 cases and 7 tumours were thoraeo-abdominal (no primary found in I case). In 103/108 cases the tumours were secreting catecholamines. The SE was 90% for the detection of the primary tumour with a SP of 100% in this series. Fox lymphnode metatases, the SE was low (35%) but the SP remained high (97%); for hepatic metastases the ~E was 93% and the SP 92%. Compared to the cyto-histologieal examination of multiple bone marrow samples, the SE of mIaG scans for the detection of bone marrow metatases was 83% a n d t h e specificity was 98%; no mIBG bone uptake could be considered as a false positive. mIBG scans performed at the time of diagnosis in neuroblastoma provide with a good sensitivity and a' very high specificity a precise evaluation of the disease extension. They also provide a baseline for further evaluation of the disease including response to therapy, remission assessment, d e t e c t i o n of postsurgical remnants and of relapses.

FP-3G3-6 F.

Scoplnaro,C.

Manni,F.S. Fasano,A. Miccheli*,G. Capuani*,I. Genuini**,A. Centi Colella S e c t i o n o f N u c l e a r M e d i c i n e , D p t . o f Experimental Medicine, Dpt.of Chemistry, University La Sapienza", **U.I.L.D.M., Rome, Italy 9 9 m T c - M I B I S P E C T IN D U C H E N N E ' S M U S C U L A R D Y S T R O P H Y (D.M.D) . Non invasive imaging of skeletal muscle is useful in t h e m a n a g e m e n t and follow up of muscular dystrophies. 5 adult normal voluntee r s 20 t o 25 y e a r s old, 8 p a t i e n t s (pts.) in paediatric age (1 - 1 2 yrs.) that underwent myocardial scan for congenital heart diseases, i0 p t s . w i t h C A D a n d 45 p t s . w i t h D . M . D . w e r e studied by 99mTc-MIBI SPECT of heart and lower l i m b s (L.L.) . F i x e d - t i m e p l a n a r i m a g e s o f c h e s t a n d L.L. w e r e a l s o p e r f o r m e d . I n i0 D . M . D . p t s . NMRI was performed. The D.M.D. pts. were d i v i d e d i n 3 c l a s s e s o f age: A) y o u n g e r t h a n i0 y r s . (15 p t s . ) , B) b e t w e e n i0 a n d 15 y r s . (20 p t s . ) a n d C) o l d e r t h a n 15 y r s . (i0 p t s . ! . Heart to m u s c l e (H/R) r a t i o w a s a s s e s s e d in planar images. In pts. without D.M.D. the H/R r a t i o s h o w e d a m i l d i n c r e a s e w i t h age, ( f r o m 2 + 0 . 5 b e f o r e i0 y r s t o 3 + 0 . 6 a f t e r 20 y r s . In D . M . D . pts. t h e H / R r a t i o r e s u l t e d 2 . 2 + 0 . 9 in c l a s s A, 4 . 9 + 2 . 6 i n c l a s s B, 6 + 2 . 5 in c l a s s C, showing a significative difference between class A and B (P<0.001) and class A and C (P<0. 0 0 1 ) . S P E C T i m a g e s o f m u s c l e s s h o w e d l a c k of uptake by vastus lateralis in 7 2 % of t h e D . M . D . pts. A g r e e m e n t with NMRI was obtained in a l l pts. H o m o g e n e o u s u p t a k e w a s o b s e r v e d in n o r m a l v o l u n t e e r s a n d r a n d o m d a m a g e in t h e p t s w i t h CAD. T h e d a t a s u g g e s t t h a t H / R r a t i o is a useful semiquantitative index of the skeletal m u s c l e d a m a g e in D . M . D . T h e 9 9 m T c - M I B I S P E C T may detect and localize muscular damage.

COMPARISON OF BONE AND 13 II-MIBG SCANNING FOR THE DETECTION OF SKELETAL AND EXTRASKELETAL NEUROBLASTOMA. The purpose of this investigation was to compare the utility of bone and MIBG scintigrapy for the detection of neuroblastoma (NB). 78 patients with known or suspected NB in whom both MDP and MIBG scans were performed within one month of each other were the subjects of this study. The scans were evaluated for both skeletal and extraskeletal disease by two experienced observers. Skeletal disease: there were 148 discrete loci of MIBG uptake and 85 foci of abnormal MDP uptake. Most of the abnormal MIBG deposits not seen with MDP were in the spine. In two cases, uptake of both tracers was diffusely abnormal. In five patients, eight deposits of MDP were due to causes other than NB- adenocarcinoma, Hodgkin's l y m p h o m a , n o n o s s i f y i n g fibroma, trauma, and urinary contamination. In five patients, MDP uptake remained positive following chemotherapy which eliminated MIBG uptake. Extraskeletal disease: 41 extraskeletal foci were identified of which 32 were MDP and 38 MIBG avid. Correlation between MIBG and MDP scans was excellent. There were no proven false positive MIBG scans. In contrast to previous studies, we found that both MIBG and MDP are excellent tracers for the detection of skeletal and extraskeletal NB. MIBG has greater sensitivity for both skeletal (97% vs. 51%) and extraskeletal (93% vs. 78%) disease. Nevertheless, a small number of lesions were detectable only by bone scanning. We recommend that both procedures be performed in evaluating neuroblastoma.

FP-3H3-1 Mecklenbeck,

U.

, Rathmann,

W.

,Vosberg,

H.

C l i n i c of N u c l e a r M e d i c i n e and the I n s t i t u t e for D i a b e t e s R e s e a r c h ; H e i n r i c h H e i n e U n i v . gOsseldorf, Germany Gastric different

Emptying forms

in

Diabetic

of d i s t u r b e d

Neuropathy:

two

kinetics.

We investigated 24 patients suffering from a type I Diabetes with proven neuropathy. The therapy showed problems in ell patients. 9 patients complained of slight gastrointestinal disorders and 6 of more serious dis-

orders i n c l u d i n g nausea, vomiting and d i a r r h o e a . The t e s t meal was composed o f a pancake l a b e l l e d w i t h 99m-Tc-Nanocolloid and 250 ml o f water l a b e l l e d w i t h 113m-In-Chloride. R e g i s t r a t i o n was done by a gamma camera over the f i r s t hour and again a f t e r 2 hours. The remaining a c t i v i t y in the stomach was c a l c u l a t e d in % a f t e r 20, 30, 60 and 120 minutes. Moreover we c a l c u l a t e d t h e time o f maximal a c t i v i t y in t h e antrum ( t max) and t h e a n t r a l emptying h a l f t i m e - ( t 1 / 2 ) . The t a b l e shows the results compared to 20 normal persons:

n = 2 4 I solid remmt 60 rain antrum t max

antrumt 1/2

n~1121

53 (44-68")%

6 (1-15) rain 146 (26-64) rain

delayed 5

87 (77 - 100)o%

26 (4 - 50) --m~88 (60 - 100) rain

accel- 7 26 (17-36) % 3 ( 1 - 4 ) m~ 123 ( 9 - 3 8 ) erated Our study shows two t y p e s o f d i s o r d e r s , one w i t h marke d l y delayed g a s t r i c emptying and another w i t h acceler a t e d t i m e . P o s s i b l y t h i s i s a sign o f d i f f e r e n t stages in the same disease depending on the kind o f neural ( a f f e r e n t or e f f e r e n t ) involvement.The high c o r r e l a t i o n between the remaining a c t i v i t y in the stomach and t h e values o f t max and t 1/2 in the antrum shows t h a t a n t r a l f u n c t i o n i s the most determing f a c t o r f o r g a s t r i c emptying in these p a t i e n t s .

553

Tuesday, 3 September 1991

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Frusciante V., Caruso N., Federici T., Barbano F., Modoni S,, Perrone E,, Petracca Ciavarella G., Valle G. Depts. of Nuclear Medicine and Gastroenterology Hospital C.S,S,, S, Giovanni Rotondo (Fg), Italia

B. O v e r b e c k , B. B r i e l e , A. H o t z e , H . J . B i e r s a c k , L. Lange, G. O t t , U. K a n i a . D e p a r t m e n t o f N u c l e a r M e d i c i n e and S u r g e r y , U n i v e r s i t y of Bonn, and D e p a r t m e n t o f S u r g e r y , W a l d k r a n k e n haus Bonn, Germany ' TC-99M-LABELED MONOCLONAL ANTIBODIES AGAINST GRANULOCYTES (BW 2 5 0 / 1 8 3 ) I N THE DETECTION OF APPENDICITIS

SOLID MEAL GASTRIC SCINTIGRAPHY USEFULNESS TO EVALUATE CISAPRIDE TREATMENT IN GAsTRo-ESOPHAGEA~ REFLUX. Delayed gastric emptying has been advocated as an important pathogenetic mechanism in gastroesophageal reflux ( GER ). Cisapride ,a new prokinetic drug devoid of central antidopaminergic effects , has been recently proposed for GER patients treatment, Aim of this study is to evaluate the effect of cisapride treatment on gastric emptying and to correlate improvement of gastric function with clinical and endoscopic performance of GER patients. We have evaluated 41 patients by SMGS (solid meal gastric scintigraphy) before beginning of cisapride, In 21/41 patient retention percentage was more than 2SD above the mean value of controls at 90 minutes (controls figure 50.6±8.6, m±sd); these 21 patients has been again submitted to SMGS after 12 weeks of treatment (i0 mg * 4), Figures of retention percentage for 21 patients were 73.5±3.4 before treatment and 55.33±9.01 after treatment; t Student value for paired data was higly significant: p<0.0005 0nly two patients after treatment showed pathologic gastric emptying. As to the clinical performance 18/19 patient with normal sciatigraphic results showed reversal of endoscopic pattern of ripe I or II esophagitis (SavaryMiller classification) to a macroscopically normal appearance and a considerable improvement of clinical symptoms. On the contrary two patients with pathologic gastric emptying after t r e a t m e n t had minimal clinical and no endoscopic improvement. We conclude that cisapride is an effective treatment in GER and that SMGS is a very sensitive and quantitative test higly correlated with clinical performance.

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Scintigraphy with Tc-99m-labeled antigranuloc y t e a n t i b o d i e s was c a r r i e d o u t in 26 p a t i e n t s with suspicion of appendicitis. S e q u e n t i a l and static i m a g i n g i n c l u d i n g SPECT o f t h e p e l v i s and abdomen were p e r f o r m e d 2 h p . i . . In a l l p a t i e n t s t h e d i a g n o s i s was c o n f i r m e d h i s t o l o g i cally or clinically. In t h e g r o u p o f 8 patients with significant positive findings in loco tipico 7 p a t i e n t s had an a c u t e a p p e n d i c i t i s and I p a t i e n t had a b e n i g n a c u t e i n f l a m m a t o r y tumor o f t h e cecum. 3 p a t i e n t s showed a questionable positive scan. One o f them had a chronic scarred appendicitis, one had d i v e r t i culitis, which was t r e a t e d c o n s e r v a t i v e l y , and one d i d n o t u n d e r g o s u r g e r y . In 15 p a t i e n t s scintigraphy was n e g a t i v e . 9 o f them d i d n o t u n d e r g o s u r g e r y and had a normal f o l l o w up. 6 p a t i e n t s had a c h r o n i c a p p e n d i c i t i s and one had a s u b a c u t e a p p e n d i c i t i s . Scintigraphy with AGAB i s f a s t and easy t o r e a l i z e and is s u p e r i o r t o t h e c e l l l a b e l i n g method f o r d i a g n o s i n g acute appendicitis. Sensitivity for the diasis of acute appendicitis in o u r s t u d y was 100 %, s p e c i f i t y was 80 %. F a l s e n e g a t i v e r e s u l t s were f o u n d in c h r o n i c or s c a r r e d non g r a n u l o cytic appendicitis in which o f t e n t h e r e had been no d e f i n i t e indication for surgery.

FP-3H3-5

Kroiss, A., Sporn, P., Weiss, W., A u i n g e r , Ch., Redl, E., A r m b r u s t e r , Ch. and N e u m a y r , A . KA Rudolfstiftung, Vienna

P. Lecouffe, H. Venel, D. Huglo, A. Adenis, J-F. Colombei, B. Wallaert, X. Marchandise M6decine Nucl6aire, Maladies de l'Apparefl Digestif & Pneumologie, CHU Lille, 59037 LILLE Cedex - France

IMMUNOSCINTIGRAPHY (IS) WITH GRANULOCYTES A N T I B O D I E S IN P A T I E N T S W I T H P A N C R E A T I T I S .

SIMULTANEOUS DETERMINATION OF PULMONARY AND INTESTINAL PERMEABILITIES IN CROHN'S DISEASE

S e p t i c c o m p l i c a t i o n s are the p r e d o m i n a n t c a u s e of d e a t h in p a n c r e a t i t i s . The a i m of t h i s s t u d y was to p r o v e t h e c l i n i c a l r e l e v a n c e of granulocytes antibody (Ab; BW250/183; B e h r i n g w e r k e , FRG). The IS was p e r f o r m e d l a b e l i n g the a n t i b o d y (Ab) in a s i m p l e p r o c e d u r e w i t h I0 mCi (370 MBq) if o n l y p l a n a r i m a g i n g w a s p o s s i b l e and 20 m C i (740 MBq) T c - 9 9 m if a S P E C T i m a g i n g was p l a n n e d . I m a g i n g w a s d o n e by a d i g i t a l c a m e r a (Elscint; A p e x 401) 4 and 14-24 hrs p.appl. In 31 p t s (17 female, 14 male; age 48±14 yrs) t h e i n v e s t i g a t i o n w a s p e r f o r m e d : 12 pts w i t h m i l d pancreatitis (m.p.) and 19 pts w i t h s e v e r e pancreatitis (s.p.) under intensive care conditions (i.c.c.). In pts with m.p. we p e r f o r m e d 19 i n v e s t i g a t i o n s : 4 pts s h o w e d a h i g h e r u p t a k e a n d w e r e s e n t u n d e r i.c.c. In pts. w i t h s.p. w e p e r f o r m e d 39 i n v e s t i g a t i o n s : in 7 pts o n l y once, in 6 pts twice, in 4 pts t h r e e t i m e s and in 2 pts four times. As all pts of t h i s g r o u p (s.p.) w e r e o p e r a t e d t h e r e l i a b i l i t y of IS c o u l d be v a l i d a t e d . So w e f o u n d a t r u e p o s i t i v e r e s u l t in 16 pts and in 3 pts a n e g a t i v e r e s u l t - t h e s e pts s h o w e d just o e d e m a of the p a n c r e a s and low l e u c o c y t e s levels. O n l y in 1 pat. w e f o u n d a h i g h e r level of t h e HAMA's. IS w i t h g r a n u l o c y t e A b s is e a s y t o p e r f o r m and gives a good information about granulocyte a c c u m u l a t i o n in p a n c r e a t i c region.

554

Latent pulmonary impairment has frequently been described in Crohn's disease (CD). Moreover, intestinal permeability is known to be increased in CD. The aim of this study was to assess simultaneously pulmonary permeability (PP) and intestinal permeability (IP) in CD. METHODS. 17 patients (18-50 age) with CD were studied. Patients studied with active CD were studied again while CD was quiescent. 13 healthy volunteers (21-45 age) acted as controls. None of the subjects was a smoker or had pulmonary symptoms or did intake alcohol before tests. IP tests were obtained from 51Cr-EDTA 24 h urinary excretion expressed as a percentage of the ingested dose. PP tests used a ~mTc-DTPA aerosol : after 2 min breathing, 60 s frames were acquired and T1/2 were obtained from exponentional fitting of the first 10 rain pulmonary clearance curves.

RESULTS. Between controls and CD, T 1/2 as EDTA excretion differed significantly (p < 0.01). Between active and quiescent CD, there was a significant difference of EDTA excretions (p < 0.05) but no significant difference of T 1/2. No correlation was found between IP and PP. CONCLUSIONS. We confirm IP is increased in active CD. We demonstrate PP is increased in CD without influence of the activity of the disease. PP impairment remains unexplained as it does not follow the same rules as IP impairment.

Tuesday, 3 September 1991

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FP-313-1

W. G. Martin. J. Adolf, K. Kirchmann, C.-D. Heidecke, J. R. Siewert, H. W. Pabst

W. BECKER A. SAPTOGINO, F. WOLF Department of Nuclear Medicine of the University of Erlangen - NiJrnberg, FRG

Nuklearmedizinische Klinik und Chirurgische Klinik, Klinikum Rechts der Isar der Technischen Universit&t MOnchen ORTHOTOPIC LIVER TRANSPLANTATION: POSTOPERATIVE MONITORING WITH THE C14-AMINOPYRINE BREATH TEST. In this prospective study we quantified liver function by means of C14-Aminopyrine Breath Test (ABT) in 20 consecutive recipients of orthotopic liver transplantation (OLT). 11 male, 9 female, mean age 43.8 years (range 14 to 64) were monitored. OLT was performed in 11 patients with liver cirrhosis, 8 patients with tumors (one cluster transplantation with a combined liver-, pancreas-, duodenal graft) and one with acute hepatic failure due to autoimmune hepatitis. Liver function of the recipients was quantified before and after OLT. Initially ABT along with routine laboratory parameters was performed daily for the first 10 days followed by larger intervals. Monitoring period is 40 to 660 days after OLT with about 600 ABT in these patients. The function of the donor liver was assessed by ABT also. Results: All patiens showed a significant increase in liver function with maximum ABT values on days 4 to 7 after grafting. The mean time to reach maximum liver capacity and maximum of ABT itself correlated well with clinical Status. Maximum ABT values were reached faster in patients with good donor ABT values, whereas onset of graft function was delayed in patients with poor donor ABT values. ABT values were heterogeneous in the first weeks. Two acute rejections were associated with dramatic ABT decrease, returning to normal ABT values following steroid pulse therapy. One histological proven chronic rejection showed a decline of liver function to values associated with hepatic failure. Conclusions: ABT is not only predictive for assessment of initial liver function, but also very sensitive for Iongtime monitoring of graft function after OLT.

SENSITIVITY AND SPECIFICITY OF A (24-H} TC-99m-GRANULOCYTE ANTIBODY SCAN IN INFLAMMATORY OR INFECTIOUS DISEASES Immunoscintigraphy of white blood cells is a promising new technique for Iocalisation of infectious or inflammatory diseases. In 56 patients this technique was performed using 555-74OMBq Tc-99m-labelled monoelonal antigranulocyte antibodies ( murine GE1against NCA-95)(BW 250/183 kindly delivered from BEHRING RKE,AG,FRG.) , which were labelled according to the mercaptoethanol technique. In 32 of them the inflammatory or infectious lesions could be proven or excluded by surgery and histology. Gamma camera images ( SIEMENS ROTA ) were performed 4 and 20 h p.i. in planar technique . 8 of 14 infectious or inflammatory lesions could be already-detected in the early scans ( 4- - 6 h. p.i. ). Sensitivity, specificity and diagnostic accuracy of these scans was 57Z 89 Z and 71~ respectively, of the 20 h scans 86Z, 89Z and 88Z. In 19 patients with with bone or bone prosthesis infections the

sensitivity, specificity and diagnostic accuracy( 87~, 81Z,84X )was lower than in patients with abdominal or soft tissue diseases(99X). The splenic antibody adcumulation was estimated to a common score. The activity was compared with the bone marrow and liver activity. The intensity of splenic uptake correlated well with the ~ripheral leukocyte count. e authors conclude, that the high diagnostic accuracy of the immunoscintigraphic technique justifies a broader application of this method ]:or Iocalisation of infectious diseases, They r e commend to perform only late scans ( 20h p.i.) as the only necessary scan, because no migration of the antibody or the antibody labelled cells through the bowel wall can be registrated.

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J.T.Locher., L.D.Frey, K.Seybold, B.Bl~iuenstein*, P.A.Schubiger* Dept.of Nuclear Medicine Kantonsspital Aarau, *Paul Scherrer Institut Vilfigen (Switzerland)

P. Theisse m F. Reusch, K. Smolarz H. Rasokat, A. Linden, H. Schicha Clinic for Nuclear Medicine, University of Cologne Joseph-Stelzmann-Str. 9, D-5000 KSln/Cologne41, Germany

DUAL ISOTOPE IMMUNOSCINTIGRAPHY OF INFECTIONS Antigranulocyte immunoscintigraphy (IS) has become a routine procedure in our institute. Since our first studies (1986) with the 1123 labeled anti-CEA MoAb-47, several Tc-99m labeled preparations became available. However, early comperative studies showed bioldnetic differencies, which are further investigated in this study. In cases of acute and chronic osteomyelitis, arthritis, infected prostheses and soft tissue abscesses planar scintigraphy and SPECT were did at 4 and 24 hrs. after injection of either 3 mCi 1-123 MoAb or 30 mCi Tc-99m MoAb. Tc-99m labeling was made by a new one step method, in which a free terminal aminogroup was tagged. This preparation was compared with the two step method of Sehwarz (using MoAb BW 250/183). Dual isotope examinations were did either by simultaneous injections of the diffexTently labeled MoAbs or by repeating the injections within 4 days. We found an almost equal functional behaviour of the labeled granulocytes and a similar quality of scans. When using Tc-99m MoAb the datas of the biodistribution were comparable despite the labeling method used, but the risk of an accidental increase of liver activity (possibly due to colloid formation) was higher for the twostep method. Diagnostically relevant differencies were found in some cases of chronic osteomyelitis, where a cold lesion was temporarely seen on early scans (in about 15% of the cases). On delayed pictures a gradually increased activity was remarked at this site. This "fillingup" phenomenon was more accentuated when an iodinated MoAb was used eventually indicating a different tracer handling at the site of an abscess. The general accuracy of both labeling methods for detecting infections was 96%; sensitivity was 97% for bone infection and 92% for other infections; specificity was 93%. The longterm immunoreaction in patients having undergone single or repeated IS was studied using two different HAMA tests. All IgG and IgM serum levels remained unchanged. We conclude that Tc-99m MoAb is more advantageous for routine use, but 1-123 MoAb is preferable in some cases of chronic infections.

SCINTIGRAPHY AND MAGNETIC RESONANCE IMAGING O F T H E B O N E M A R R O W IN AIDS-PATIENTS In immundeficiency abnormalities of bone marrow (BM) as part of the immunologic system must be expected. Such changes also were shown by B M biopsy studies.By this study in 41 AIDS patients(pt)it was proved how often B M changes occur with scintigraphy (Sc) and magnetic resonance imaging (MRI), and whether a relation exists between these changes and the clinicalfindings, therapy and W R classification.39 male and '2female pt (age 25 - 68 years;x=42 years), all HIV-antibody positive,were examined by TI- and T2-weighted M R I of the lumbar, pelvicand femoral B M (N=38) as well as by whole body scintigraphy of B M (N=36). Sc and M R I changes were graded in 3 groups (normal, reactive and focal lesions).In addition, M R I signal intensities of 18 B M areas were quantified by ROI-technique and compared to the values of 10 healthy volunteers.Six of the pt had a malignant lymphoma. Seventysix % of the Sc and 82% of the M R I examinations showed B M abnormalities, and 75% of the pt (24/33) with both methods. The pathological Se and M R I patterns consisted of homogeneous and/or focal changes. Although the Sc and M R I abnormalitiesof B M became more frequent with increasingWR-class and hematologicaldeviations as well as decreasing number of T-helper-cells,no close correlation with these parameters occurred. Thirtyseven % of the pt with Sc and/or M R I changes had a higher amount of T-helper-cells(> 100/till, 50% a WR-class 4 or lower, and 20% showed no hematological deviations. No correlationcould be found between the applicationof antibioticdrugs or azidovudine (AZT) and the frequency of Sc or M R I B M changes. The deviationsof Sc and M R I patterns occuring in most of the patients may correspond to the morphologicaldeviationsin B M biopsies reported previously by other authors. The presented data showed that in AIDS-pt in numerous cases widespread changes of B M exist.These abnormal B M findings are detectableby Sc and M R I as complementary B M imaging methods, even in less advanced AIDSstages.The identifiedpathologicalB M findingsm a y be due to reactive changes in mQst cases,however, partly caused by focalB M necrosisor infiltration due to malignant lymphomas. Further studies are required to assess the role of B M imaging in the diagnosticand followup of AIDS disease in HIV-positivept.

555

Tuesday, 3 September 1991

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Wednesday, 4 September 1991

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F. JAMAR, N. LENERS, C. BECKERS, A. FERRANT. Centre de M4decine Nucl@aire, University of Louvain Medical School, UCL 54.30, av. gippocrate 54, 1200 Brussels, Belgium•

CI. de Labriolle-Vaylet, MT. Doloy, M. Salat-Trepas, A. Petiet and N. Colas-Linhart. Dept. de Biophysique des Traceurs Radioactifs. Facultg X. Bichat. 75018 PARIS. RADIOBIOLOGY OF Tc 99mHMPAO LABELLED LYMPHOCYTES.

PROGNOSTIC FACTORS (ITP) : PLATELET ANTIBODIES.

I N I M M U N E T H R O M B O C Y T O P E N I C PURPURA SURVIVAL AND P L A T E L E T - A S S O C I A T E D

In order to define prognostic factors in ITP, the clinical and laboratory data of 44 patients were retrospectively analyzed• There were 28 women and 16 men (mean age : 43 yr). All patients had a platelet survival study (PSS) using Indium-ill labelled autologous (n=31) or homologous (n=13) platelets. Platelet-assoeiated immunoglohulins (IgG and IgM) as well as platelet-bound complement (%d) were measured (radioactive antiglobulin consumption test). Platelet count at diagnosis, lowest platelet count during the clinical course, age, sex and the number of megakaryocytes in a marrow aspirate were also evaluated. The patients were classified in 3 groups according to their outcome : complete response if the platelets rose over 150 109/1, partial response if the platelets reached 50-150 109/1 and failure if the platelets remained below 50 109/1. By both univariate and multivariate analysis, platelet-bound %d and sex had a prognostic value, respectively at p=O.O02 for C3d (univariate and multivariate), p=0.015 (univariate) and p=0.008 (multivariate) for sex. Neither the parameters of PSS, the antiplatelet antibodies (IgG or IgM) nor the other parameters had a statistically significant prognostic value. In conclusion, we suggest that a high level of platelet-bound %d and female sex are factors of good prognosis in ITP.

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•

_M_._I_._Os_h_t___~aJih__ and V.A.Semionkln , D i v i s i o n of A p p l i e d B i o p h y s i c s a n d F a c u l t y of E x p e r i m e n t a l Physics, U r a l P o l y t e o ~ m i o a l Institute, Sverdlovsk, 620002, U S S R

OXYHEMOGLOBIN RADIOLYSIS STUDIED BY MOSSSALER SPECTROSCOPY The p r o b l e m of r a d i a t i o n - i n d u c e d dam.age in h e m o g l o b i n is a subject of a n u m b e r of investigations. N 6 s s b a u e r spectroscopy was used for a n a l y s i s of iron-containing compounds d u r i n g h e m o g l o b i n radiolysis. N S s s b a u e r s p e c t r a of the f r o z e n solutions of h u m a n adult o x y h e m o g l o b i n in e r y t h r o c y t e s e x p o s e d to 7 - i r r a d i a t i o n w i t h doses of ~'100, ~300 a n d ~ 6 0 0 k G y were measured. MSssbauer speotl~a w e r e f i t t e d using five components. ~ h e s e w e r e o x ~ h e m e g l o b i n , d e o x y h e m o g l o b i n and c o m p o n e n t s m a r k e d I, 2 a n d 3. U s i t ~ M ~ s s b a u e r ~%vperfine p a r a m e t e r s of e a c h component the v a l e n c e / s p i n states of iron ions were determ i n e d a n d p o s s i b l e c o m p l e x e s were c o n s i d e r e d . T h e most p r o b a b l e o o m p o m l d s for c o m p o n e n t s I, 2 a~id 3 ~vere h e m a t i n a n d / o r ~ - o x o d i m e r s , methemoglobin by@oxide 8~id/or hemiohromes, and the h i g h s p i n l~e(III) complex, respectively. C h a n g e s of the r e l a t i v e a/~eas of M ~ s s b a u e r s u b s p e o t r a of all c o m p o n e n t s (its c o n t e n t in samples) v e r s u s doses wel~ e v a l u a t e d a n d the p r e s e n c e of the h i g h a n d l o w spin aquometh e m o g l o b i n was indicated. P o s s i b l e p a t h w a y s of ox~rhemoglobin radiolysis b y 7 - i r r a d i a t i o n of e r y t h r o e y t e s were evaluated on the b a s i s of the M 6 s s b a u e r s p e c t r o s c o p y data.

556

Tc 99m labelling is routinely performed on mixed leukocytes. The presence of Tc 99m within the cell, and probably in the nucleus may result in significant cell damage, specially for lymphocytes if the radiation dose delivered to those sensitive cells is high. Actually high values (6 to 7 Gy to the cells) were derived from experimental data (13 MBq for 5 x 107 cells) and physical calculations using Berger's scaled point kermel. In order to control these results, we have performed biological dosimetry using chromosomal aberrations countings (dicentrics and rings). The biologically determined absorbed dose is in agreement with the physical results. In addition, labelled T lymphocytes were grown in the presence of Phytohemagglutinine and Interleukine 2 for two weeks. The plating efficiency of the labelled lymphocytes was 0.8 % (26 % for the unlabelled lymphocytes). We conclude that most labelled lymphocytes are dead according to the radiobiological definition, but the presence of a few cells with stable translocation can not be excluded. Further studies are necessary to demontrate this hypothesis,

Wednesday, 4 September 1991 FP-4DI-1 P Bartenstein, JS Duncan,VJ Cunningham, DJ Brooks, DR Fish, G Sawle, SK Luthra, RSJ Frackowiak. MRC Cyclotron Unit, Hammersmith Hospital, Du Cane Road and Epilepsy Research Group, Institute of Neurology, Queen Square, London, UK. Klinik fiir Nuklearmedizin, Universit~it Miinster, A.-Schweitzer-Str., FRG llC_DIPRENORPHIN E KINETICS IN ABSENCE SEIZURES The neuro-anatomical basis and pathophysiology of generalized absences remain unclear. The peri-ictal release of endogenous opioids has been demonstrated in animal models. We performed PET scans with a high resolution camera (CTI 931-08/12) in 8 patients with generalized epilepsy. The study was approved by the local ethical committee. CBF was measured interictally with C1502, after which 300-500 MBq of the Opioid-receptor ligand l l C Diprenorphine was injected and a dynamic study over 90 min was performed. Serial absences were precipitated by hyperventilation for 10 minutes, starting 30-40 rain after injection of Diprenorphine. The EEG was monitored continuously. Absences, with generalized spike-wave discharges on the EEG, occurred for between 10% and 51% of the activation period. 8 normal subjects of similar age were investigated under identical circumstances. No individual (normal or patient) exhibited any focal rCBF changes. Quantification of Diprenorphine binding showed an increased washout following seizures in brainstem (p_<0.01), posterior cingulate (p<0.05) and lateral parietal cortex (p<0.01). Other cortical areas showed an increased washout, but this was not significant. Fitting of individual patient's data to a computer based simulation of ligand-receptor interaction showed periictal displacement of >15% in brainstem (5 patients), cingulate posterior (6), lateral parietal (7), lateral temporal (4), prefrontal (4), premotor (4), medial parietal (1) and medial frontal (1) cortex. With neither method was any displacement found in thalamus, basal-ganglia, cerebellum or occipital and sensorimotor cortex. Further analysis of averaged data with a 2-compartment model showed a change in K3 after activation of 15-40% in brainstem and areas of neocortex.These results indicate the release of endogenous opioids at the time of serial absences at these sites, that may have an important role in the suppression of generalized absences.

Wednesday, 4 September 1991

FP-4D1-2

FP-4D1-3

Z. Szabo, D.F. Wong, S.Sostre, H. Ravert, U. Scheffel, R.F. D a n n a l s , H. R i v e r a - L u n a , C. Seki, T.K. N a t a r a j a n , E.E. C a m a r g o , H.N. W a g n e r Jr. The J o h n s H o p k i n s M e d i c a l I n s t i t u t i o n s , B a l t i m © r e USA.

E.E. Camarqo, Z. Szabo, J.M. Links, S. Sostre, R.F. Dannals, and H.N. Wagner, Jr. The Johns Hopkins Medical Institutions, Baltimore MD, USA.

D I S T R I B U T I O N OF H I S T A M I N E HI R E C E P T O R S IN THE B R A I N I N V E S T I G A T E D W I T H [ C - I I ] P Y R I L A M I N E PET AND FACTOR ANALYSIS The h i s t a m i n e HI r e c e p t o r s of the b r a i n h a v e b e e n s u c c e s s f u l l y imaged w i t h [ C - ] l ] p y r i l a m i n e . The g o a l of this s t u d y was to s t u d y the p a t t e r n s of p h a r m a c o k i n e t i c s of [ C - l l ] p y r i l a m i n e in d i f f e r e n t r e g i o n s of the b r a i n and c o r r e l a t e t h e m w i t h HI r e c e p t o r d e n s i t i e s . M e t a b o l i s m s t u d i e s showed that in m i c e up to 30 mln p.i. 96 % of [ C - l l ] p y r i l a m i n e r e m a i n e d c h e m i c a l l y intact in the brain. In h u m a n s e x t r a c e r e b r a l m e t a b o l i s m of the t r a c e r was s l o w and at 20 m i n u t e s p.i. the f r a c t i o n of m e t a b o l i t e s in the p l a s m a was less than 50 %. PET s t u d i e s w e r e p e r f o r m e d in four n o r m a l v o l u n t e e r s . F a c t o r a n a l y s i s of d y n a m i c PET data r e v e a l e d two c l u s t e r s of b r a i n regions. C l u s t e r I w i t h the f r o n t a l - t e m p o r a l - p a r i e t a l cortex, h y p o t h a l a m u s and g y r u s c i n g u l i and c l u s t e r II w i t h the o c c i p i t a l c o r t e x and c e r e b e l l u m . The f a c t o r v a l u e s d e m o n s t r a t e d a statistically significant linear correlation w i t h HI r e c e p t o r d e n s i t i e s in t h e s e r e g i o n s as m e a s u r e d in p o s t m o r t e m h u m a n b r a i n tissue. T h e s e r e s u l t s s h o w that [ C - l l ] p y r i l a m i n e may be a u s e f u l m a r k e r of the HI r e c e p t o r s s i n c e its r e g i o n a l c e r e b r a l k i n e t i c s r e f l e c t s local d e n s i t y of t h e s e r e c e p t o r s .

VAR/ABILIq~ IN GLOBAL 2-(18F)FLUOI~O-2DEOXY-D-GLUOOSE [F-18] FDG BRAIN METABOLISM?.

WHAT CAUSES ~

This study investigated the influence of biological and technical factors on variations of global and regional cerebral metabolic rate of glucose (d~ggl) measured with [F-18] FDG. Twelve male volunteers (2240 yrs) were investigated on 3 or 4 occasions for a total of 42 studies. We calculated the variance/ oovariance of the following parameters: d~l~gl, six parameters of the blood clearance of [F-18] FDG, hour of injection, peak time of blood radioactivity, six ccmponents of the operational equation (nonradioactive blood glucose concentration, brain radioactivity, two integrals, numerator and dencad_nator). There was correlation among these six conl~nents , except for non-radioactive blood glucose. However, correlation between the cMRgl and the individual cmmponents of the operational equation was poor. The inter and intrapersonal c M ~ l varianoes were 13.8% and 7.1%, respectively. In centrast, variances of the numerator and d e n ~ t o r of the operational equation were 34.6% and 32.6%, respectively, and were always in the same direction. No correlation was found between ci~Rgl and the technical factors in the operational equation. Factor analysis demonstrated that two factors were responsible for 80% of the variance and that 70% was due to Factor I, which included caudate, putamen, cingulate, thalamus, frontal cortex and ~ r a l cortex. These structures are involved with multiple ccaplex functions, frmm autonomic control to behavior and emotions. Their intrinsic metabolic variability, along with the basal metabolic processes continuously going on in the brain, may be the best explanation for the variance encountered in our investigation.

FP-4D1-4

FP-4D1-5

K . - J . L a n g e n L D. Z i e g l e r z, M. K. LokenL H. HerzogL T K u w e r t I, F.A. Gries 2, ],.E. F e i n e n d e g e n 1 t Institute of Medicine, Research Center ,JiiJich, FRG 2 Diabetes Research I n s t i t u t e , D~'isseldorf, FRG

D.Scholz 1, H . J a b l o n o w s k y 2, T . K u w e r t 1, M.LokenL H.Herzog t, L . E . F e i n e n d e g e n 1

REGIONAL CEREBRAL GLUCOSE CONS!iMPTION IN DIABETIC PATIENTS WITH AND WITHOUT NEIIROPATHY P r e v i o u s s t u d i e s h a v e r e p o r t e d a d e c r e a s e d regiorlal carebral metabolic rate for glucose (YCMRGIc) in patients with insulin dependent diabetes rael]itus (IDDM) (M. G u t n i a k c t a h , Am. J. P h y s i o l . 258: E 8 0 5 - E 8 1 2 , 1990). T h e p u r p o s e of t h i s s t u d y w a s to e v a l u a t e rCMRGIc in 1DDM with and w i t h o u t d i a b e t i c n e u r o p a t h y . rCMRGlc was determined using Positron Emission T o r a e g r a p h y and t h e 1 8 F - F l u o r o d e o x y g h l c o s e method in 6 male IDDM p a t J e n l s with n e u r o p a t h y ( a g e 44.8 + 12.0 y e a r s ) , 9 male IDDM p a t i e n t s w i t h o u t n e o r o p a t h y (5 hat] early manifest, 4 ]ongterm manifest diabetes, age 37.0 ± 15.6 years) and 10 ~nale normal volunteers (age 43.3 + 12.3 years). Some of the IDDM patients with neuropathy additional~y suffered from retinopathy (n=5) and b e g i n n i n g n e p h r o p a t h y (n=6). Compared to n o r m a l s rCMRGlc w a s s i g n i f i e a n l d y r e d u c e d in IDDM w i t h n e u r o p a t h y (22.0 + 2.0 v e r s u s ,94.6 + 3.1 Ilrnc l/J 00g x rain., p
W.HohenforstL

1) I n s t i t u t e of Medicine, R e s e a r c h C e n t e r Jtilich, and 2) Department of Internal Medicine, University of Diisse}dorf, F.R.G. CEREBRAL GLUCOSE HIV SEROPOSITIVE SUBJECTS

CONSUMPTION MEASURED BY PET NEUROLOGICALLY ASYMPTOMATIC

IN

Previous work has found a diminished regional glucose c o n s u m p t i o n (rCMRGlc) in p a t i e n t s w i t h n e u r o l o g i c a l m a n i f e s t a t i o n of AIDS. The aim of t h i s s t u d y w a s to i n v e s t i g a t e i f s i m i l a r r e s u l t s a r e o b t a i n e d in n e u r o l o g i c a l l y asyraptornatio HIV s e r o p o s i t i v e s u b j e c t s . Cortical a n d s u b c o r t i c a l rCMRGlc h a s been e v a l u a t e d in 17 n e u r o l o g i c a l l y i n t a c t HIV s e r o p o s i t i v e p a t i e n t s (CDC II-IIl) using mF-fluorodeoxyglucose (FDG) and p o s i t r o n e m i s s i o n t o m o g r a p h y (PET). T h e s e p a t i e n t s , 1 f e m a l e a n d 16 m a l e s , r a n g e d in a g e from 25 to 58 y e a r s (mean 37 y e a r s ) . 11 n o r m a l a d u l t m a l e s w i t h a c o m p a r a b l e a g e r a n g e s e r v e d as c o n t r o l s . Each of t h e 28 p a r t i c i p a n t s in t h i s i n v e s t i g a t i o n r e c e i v e d an i.v. i r 0 e c t i o n of 200 to 260 MBq FDG 30 m i n u t e s p r i o r to a PET s t u d y p e r f o r m e d w i t h a S c a n d i t r o n i x PC 4 0 9 6 - 1 5 W B ' m u l t i s l i c e s c a n n e r (7 mm r e c o n s t r u c t e d i m a g e r e s o l u t i o n ) . C o r r e c t i o n s for a t tenuation were done u s i n g transmission scans. The rCMRGle for t e n r e g i o n s of b r a i n were d e t e r m i n e d from a s t a n d a r d i z e d s e r i e s of c i r c u l a r c e r e b r a l a r e a s . T h e m e a n c o r t i c a l rCMRGIc in t h e n o r m a l s r a n g e d from 27.6 to 36 ~ m o l / ] 0 0 g/rain. One s u b j e c t of t h e HIV group s h o w e d a m e a n c o r t i o a l rCMRGlc of 56.1 ~mol/'lO0 g/rain, t h e r e f o r e he w a s e x c l u d e d of t h e s t u d y . - T h e rCMRGIc f o r all t e n r e g i o n s w a s f o u n d to be c o n s i s t e n t l y lower (11% on t h e a v e r a g e ) for t h e HIV g r o u p t h a n f o r t h e controls (range 6-19%) with statistically significant dec r e a s i n g in 6 of t h e 10 r e g i o n s (p<0.05, o n e s i d e d t - t e s t ) . T h i s r e s u l t s i n d i c a t e t h a t PET can r e v e a l s i g n i f i c a n t r e d u c t i o n s in g l u c o s e c o n s u m p t i o n in HIV s e r o p o s i t i v e s u b j e c t s b e f o r e t h e o n s e t of n e u r o l o g i c a l s y m t o m s . T h u s , PET m a y be u s e f u l in f o l l o w i n g t h e c l i n i c a l c o u r s e of t h e disease.

557

Wednesday,

4 September

1991

FPI4D1-6

FP-4GI-1

R.C. Verma, L.R. Bennett, M.P. Can, M.A.Mandelkern, F. Kioumehr, G. Mathisen, J. Harker, C. Wasterlain, F. DeLeon-Jones, L.R. Penix, H.L. Poer, J. Ropchan, W.H. Blahd, and I. Yaghmai. Olive View-UCLA Medical Center, Sylmar, California, USA

P.H.Cox, M.Pillay and O.H.W.Sch~nfeld. Or. Oeniel den Hoed Cancer Centre, P.O.Box 5201, 3008 AE Rotterdam NL.

Neuroimaging in Acquired Immune Deficiency Syndrome

TECHNETIUM LABELLEO SOMATOSTATINE FOR IN VIVO TUMOURLOCALISATION,

The purpose of this study is to identify early markers of AIDS dementia complex. Fifty-two symptomatic (Group A) and 15 asymptomatic (Group B) HIV-1 seropositive, and 8 healthy (Group C) subjects have undergone neuropsyehological tests (NPT), CT/MR and PET 18F-fluorodeoxyglucose (FDG) scans. The mean age (years) was 39 in A, 34 in B, and 36 in C. The mean CD 4 lymphocyte count/eumm was 271 in A and 742 in B. Sixty-three percent of Group A belonged to Waiter Reed Stage 6, and 70% were on AZT therapy. Forty 18F-fluorodeoxyglucose (FDG) PET Scans have been performed. Significant (p<0.02) increased uptake of FDG in the striatum was present in A, versus B and C together. This demonstrated a modest correlation (r=0.5) with CD 4 lymphocyte count and atrophy. Significantly (p< 0.05) increased frequency and severity of cortical atrophy on CT/MRI was noted in A versus B and C individually or together. White matter lesions were present in 8 of A and i of B. Cortical lesions were noted in 5 in A and 1 patient each in B and C. Mean NPT scores revealed significant (p< 0.05) impairment in tests of speed of information processing, abstraction and reasoning in Group A versus B and C. On follow-up studies, 20 subjects demonstrated a decline of 27% in mean CD 4 cell count over a mean interval of 8 months. Minimal increased atrophy was noted with no change in NPT scores. In conclusion, cortical atrophy, striatal FDG hypermetabolism, and abnormalities in cognitive flexibility in Group A versus B or C, implicate the subcortical as well as frontal regions. (Supported by Universitywide AIDS Task Force, Calif.)

Analogues of somatostatin labelled with iodine 131 or with indium 111 show a rapid looalisation in endocrine tumours sufficient For scintigraphic Iooalisation. Somatostatln itself has a rapid biological turnover but was considered to be unsuitable for radiolabelling. It does however contain sulphohydrylgroups which can be exposed to make them available as binding sites for Technetium ggm. Somatostatln was incubated with a solid phase electron donor {SPEO) at to expose the Technetium binding sites. Sodium perteohnetata solution was than added and the mixture incubated to complete labelling. The labelling efficiency was ~ BO%, separation of free Technetium was unnecessary because this becomes bound to the SPEO end is retained in the vial. 22MBq of labelled compound was administered to rats bearing cole-rectal carcinoma end the biodistributian'was studied by gamma camera scintigraphy. Accumulation was observed in the liver, Kidneys and urine. Tumour uptake was maximal at 2 4 min post injection and despite a rapid fall in blood levels there was no significant leaching of activity from the tumour. The tumour to muscle uptake retio's were 5:1 which compares qavourably with those reported qor the labelled analogue octreotide of 3:1. That the tumour accumulation of Technetium was related to the somatostatin binding to receptors in the tumour was controlled by treating one group of tumour bearing animals with suramine, to block the receptor sites, prior to administration o< the labelled complex. No tumour uptake was observed. A Technetium $@m somatostatin complex useful es a radiopharmaceutioal to detect endocrine related tumours is a realistic possibillity.

FP-4G1-2

FP-4G1-3

A. SIGNORE, V. FIORE, G. GIULIANO, G. RONGA, F. SCOPINARO, P. POZZILLI and D. ANDREANI. Servizio Medicina Nucleare and Endocrinologia I, Clinica Medica II; Sezione di Medicina Nucieare, Dipartimento Medicina Sperimentale; University of Rome "La Sapienza", Italy.

E Ur, *J Bomanji, *SJ Mather, *KE Britton, A Grossman and GM Besser; Departments of Endocrinology and *Nuclear Medicine, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE United Kingdom.

DETECTION OF ABNORMALITIES OF INSULIN METABOLISM IN DIABETIC PATIENTS BY COMPARTMENTAL ANALYSIS OF 1231INSULIN KINETICS. Abnormalities in insulin activity have been detected in both Type 1 and Type 2 patients. There are a few techniques available to study the in vivo insulin activity and among-these the kinetics of 1231.A14_insulin. This technique allows the study of receptor binding and post binding events which have been suggested to be altered in diabetic patients. The aim of our study was to evaluate the hepatic kinetics ol 1231.insulin applying the principles o! compartmental analysis. We designed a model with two compartments representing the liver separate by from other tissues. We studies 8 Type 1, 8 Type 2 diabetic patients and 8 normal subjects, age and weight matched. All subjects were injected i.v. with 37 MBq of 1231A14-insulin and gamma camera images were acquired for 40 min at frame rate of 1 image/15 sec. Regions ot interest were drawn over the liver and the heart and time-activity-curVes (TAC) were generated. Heart TAC was corrected for free 1231 contamination and liver TAC was corrected for blood flow subtraction. The resulting cdrves were fitted with a biesponential function, The constants K1 and K2 and related Tl/2 were calculated. Metabolic parameters (fasting blood glucose, HbAlc, Cpeptide) were also measure{J and correlated with parameters obtained from insulin kinetics. The rfiean+SD of Tl/2(1) and Tl/2(2), for the liver TAC, were 636+163 and 69.5+9.5 in normal subjects; 688+219 and 74.1+15 in Type 1 diabetics; 918+333" and 71.0+12 in Type 2 diabetics (*p<0.03 vs N.S ) indicating a normal insulin receptor binding kinetics but a delayed post-binding insulin metabolism in Type 2 diabetic patients only. Plasma insulin disappearance curve, obtained by PCA precipitation of blood samples taken during the study, confirmed a delayed plasma appearance ol free 1231 in Type 2 diabetic patients. In conclusion, we demostrate in vivo for the first time an alteration of insulin post-binding kinetics in type 2 diabetic patients. No significant correlation was found between insulin kinetics results and metabolic parameters, suggesting the influence of genetic factors in the abnormalities of insulin receptors in type 2 diabetes. The quantification of defect is possible by using this technique and the effects of different therapeutical approaches can be evaluated.

SOMATOSTATIN-RECEPTOR ACROMEGALY

558

IMAGING

IN

A number of neoplasms, including growth hormone secreting pituitary adenomas are known to express somatostatin receptorS, and we have found the use of an 123I-labelled somatostatin analogue helpful in their visualisation and functional characterization. We have looked at 13 patients with Acromegaly using TyrLoctreotide labelled with approximately 200 MBq of 123I. In each case planar and single-photonemission computerised tomographic (SPECT) images of the head were obtained 10 minutes, four hours and 24 hours after injection of 50/xg of the radiopharmaceutical using a large-field of view gamma camera. Our results demonstrate a significant pituitary tumour uptake in ten out of the 13 acromegalics. The three acromegalic patients who failed to show somatostatin uptake in their turnouts on scanning also failed to show GH suppression on octreotide therapy. One acromegalic patient who demonstrated uptake pre-operatively showed no pituitary uptake after trans-sphenoidal hypophysectomy. It therefore appears that a radiolabelled somatostatin analogue may be extremely useful in the visualization and functional characterization of pituitary somatotrophin adenomas.

Wednesday, 4 September 1991

FP-4G1-4 ~J~J~;~, J. MARIENHAGEN, R. SCHEUBEL U. SCHRELL, W.H. BAKKER, W.A.P. BREEMANN, A. SAPTOGINO, F. WOLF, Department of Nuclear Medicine, Internal Medicine, Neurosurgery of the University of Erlangen-NUrnberg, FRG and Department of Nuclear Medicine of the Unlversity Rotterdam. The Netherlands J-123-LABELLED TYR-3-OCTREOTIDE SCANS IN ENDOCRINE NEOPLASMAS Different endocrine-related tumours contain large numbers of highaffinity somatostatin receptors. J-123-1abelled tyr-3-octreotide(synthetic derivate os somatostatin) was used to Iocalised such benign or malignant turnouts or their metastases with the gamma-camera. TYR-3-SMS-201-995 was labelled according to a chloramin-T-protocoll which has been previously described in detail.(1) 20 patients ( meningeomas n=2, multiple endocrine neoplasia n=2, acromegaly n=l, carcinoids n=lO, bronchogenic carcinoma n=l, insulinoma n=2,gastrinoma n=2)were investigated with 1OO-185MBq J-123-Tyr-3--SMS in planar and SPECT technique between 10rain and 4h p.i.. Without the meningeoma patient all others had signs and symptoms of local tumor infiltration or elevated serum gastrin. ACTH calcitonin or GRH levels or 5 - hydroxyindolacid excretion. n 3 patients with a positive receptor status m-vitro (insulinomas n=2 meningeoma n=l) the primary tumours and all metastases coJd be Iocalised. 3 of 5 patients with known metastases under successful somatostatin treatment ( carcinoids ) showed positive uptake in their metastases. One male patient with gastrinoma demonstrated pathologic abdominal uptake in a still unknown m etastase. Other positive receptor uptakes could be seen in meningeoma(n=l), malignant gastrinoma (n=l)and bronchogenic carcinoma (n=l). One false positve uptake could be seen in an an osteonecrosis of the femur. All the other patients had completely negative scans. All scans were positive 10min p.i. Late ve no additinal information. ese results demonstrate the clinical usefulness of somatostatin since binding is predictive of biological activity and an initial scan demonstratrng Iocalisation might enable one to consider therapy with octreotide. Moreover identification of metastases not detectable by standard CT and MR might make it possible to carry out more precise and aggressive surgery. (1) BAKKER et al. JNM 31; 1990 ; 1501

FP-4G1-5 H.Vosberg, L.Nyitrai, G.Georgescu, R.Larrass C.Reifenrath Clinic for Nuclear Medicine, Heinrich-HeineUniversit~t DOsseldorf, Germany THYROIDAL

FP-4G1-6

FP-4HI-1 M.~mal,

The a i m o f t h i s s t u d y was t h e c o m p a r i s o n o f a new d e v e l o p e d IRMA t o d e t e r m i n e hTg w z t h a conventional RIA system. For this reason 227 serum samples of 214 patients were assayed. The p a t i e n t s were divided into 3 groups: a) in remission(n=161);b) with residual thyroid tissue (n=34); c) with metastases or relapse (n=17). All patients had previous thyroidektomy and 1-131 therapy. Methods: Determination of serum conc. of TT4, FT4, TSH; hTG: r e c o v e r y t e s t s , ( expected: 1004; normal range: 80-12096), lower detectzon llmit ( L D L ) , TAB. Results: Normal recovery : RIA: 95~ ; IRMA: 98~ (all samples). LDL: RZA: 7 ng/ml; IRMA: 1 ng/ml. Group a) both assays: v a l u e s < LDL: 9 3 , 6 ~ ; a b n o r m a l r e c o v e r y RZA: 2,6~,IRMA: 1,34. R I A < LDL a n d I R M A > LDL : 5 4 G r o u p b } b o t h a s s a y s > LDL : 5 6 ~ ; b o t h a s s a y s < LDL 1896; R I A < LDL a n d IRMA > LDL : 2 0 4 ( a l l patients were off 1-thyroxine medication). Group c) b o t h a s s a y s > LDL: 7 5 4 ; R I A < LDL and IRMA > LDL:204; one patient h a d I R M A
t o t h e l o w e r LDL o f t h e IRMA a n u m b e r o f p a tients who w e r e p r e v i o u s l y "Tg-normai ~ had to be c l i n i c a l l y reclassified. 4. Despite of the l o w e r LDL t h e s p e c . o f t h e IRMA i s n o t a l t e r e d .

KINETICS

Euthyroid patients show a strong correlation between thyroid size and P. Iodine exposure leads to considerably reduced E with largely unaltered P, thus allowing P-images even with nearly no TcU. T4-suppression leads to concordant reduction of P and E with unchanged extraction fraction (E/P). Hyperthyroidism leads to a higher increase of P than of E. In autono~ moes nodules both, P and E are higher than in the surrounding t~ssue, but E/P is the same, indicating unchanged cellular function in autonomous nodules with only a higher amount of working cells per volume.

A.Hotze , A.Bockisch, S.Briele, H.d.Biersack Dept.Nucl.Med., Univ.of Bonn, F.R.Germany

D E T E R M I N A T I O N OF SERUM HUMAN T H Y R O G L O B U L I N ( H T G ) W I T H A NEW I R M A I N P A T I E N T S W I T H THYROID C A R C I N O M A

PERTECHNETATE

Tc-uptake (TcU) measurements are widely used iN the assessment of diffuse and focal autonomy. To derive information in physiological terms like perfusion (P) or extraction (E), deconvelution analysis has been apllied. Time-activity curves over thyroid and heart during 30 min. p.i. were derived with a computerized camera. Deconvolution analysis produced transfer functions (TFs) describing pertechnerate transport in the thyroid. All TFs showed an initial perfusion peak followed by a parenchymal monoexponential clearance. Thus, a 2compartment model could be postulated and values for P, E and Tc-wash out from the thyroid (U) could be calculated. Using a 3x3 pixel window sliding over the entire matrix, TFs could be calculated for every pixel, giving 3 new matrices with regional values for P, E, and W.

H.Kdrn~,

D.Zahdlka

Charles U n i v e r s i t y Prague and Czechoslovak A c a d e m y of Sciences Salmovskd 3, 120 O0 Prague 2, Czechoslovakia EXTRACTION OF UNKNOWN IHAGE STRUCTURES BY F A C T O R - L I K E MULTIPLE IMAGE SUBTRACTION Some p r o b l e m s i n h e r e n t in image subtraction (due to motion, attenuation, scatter, etc.) c a n be o v e r c o m e when m o r e t h a n t w o i m a g e s a r e subtracted, the specific distortion of each is of different weight. The p r o c e d u r e suited to the purpose is factor analysis. However, i f J u s t one s t r u c t u r e of interest i s t o be found (as it is usual in scatter correction or d u a l - i s o t o p e imaging), eigenvectors need not be extracted. Original image sequence is considered to be a sum of two images specifically weighted to form its respective images= the image of interest end the other one which contains everything else (background, noise, motion artifacts) what should be rejected. As the intrinsic structure of the latter image is not important, the image is considered to be orthogonal to the image of interest. This a s s u m p t i o n and partial knowledge of the image (a f e w r e f e r e n c e points where the st-ructure of interest Is not present) are sufficient enough to extract complete image of the structure of interest, Results with phantoms indicate 30~ improvement in contrast-to-noise ratio when t h e n u m b e r o f s u b t r a c t e d images increases from 2 to 4. An advantage of the method is its simplicity and speed which favour its practical usefulness, Spectrum of different applications in image processing is demonstrated.

559

Wednesday, 4 September 1991

FP-4H1-2

FP-4H1-3

K. S. Nijran and A. S. Houston* Nuclear Medicine Dept. Charing Cross Hospital, London, U.K. *Nuclear Medicine Dept. RNH Haslar, Gosport, U.K.

J.T. Kuikka, M. Tenhunen-Eskelinen, E. L~nsimies Kuopio U n i v e r s i t y Hospital, Kuopio, Finland

A QUANTITATIVE EVALUATION OF CURRENTMETHODSOF FADS APPLIED TO RENAL DYNAMIC STUDIES.

EVALUATION OF PERFUSION-VENTILATION HETEROGENEITY IN THE LUNGS USING FRACTAL DYNAMICS

The aim of f a c t o r analysis of dynamic structures (FADS) is to represent a dynamic radionuclide study as f a c t o r curves and f a c t o r images. There are c u r r e n t l y f i v e FADS methods, namely apex-seeking; c l u s t e r analysis; i n t e r s e c t i o n method; simple structure; and s p a t i a l constraints. This work reports the f i r s t r e s u l t s of a detailed q u a n t i t a t i v e comparison of these methods. Each method was applied to 40 individual kidneys obtained from 20 Tc-DTPA dynamic studies.Three f a c t o r s curves were extracted f o r each kidney, corresponding to parenchyma, c o l l e c t i n g system and blood background structures. Whole kidney t r a n s i t time, parenchymal t r a n s i t time and glomerular f i l t r a t i o n rate (GFR) were estimated from these

I t has been shown that a l l neural, e p i t h e l i a l and endothelial branching systems are f r a c t a l s in one or more features. We have applied f r a c t a l analysis to estimate the h e t e r o g e i n e i t y of the perfusion-to-vent i l a t i o n r a t i o of the dynamic Tc-99m lung scans. V e n t i l a t i o n study was performed in patients suff e r i n g from various lung diseases using Tc-99m DTPA labeled aerosols. A dynamic study, 50 frames each 30 sac was registered in PA p o s i t i o n . Immediately a f t e r the v e n t i l a t i o n study, a perfusion study in same posi t i o n was followed. A f t e r correction f o r v e n t i l a t i o n background, the p e r f u s i o n - t o - v e n t i l a t i o n r a t i o was calculated and imaged. This image was divided into I00 subregions (50 per lung) and the regional r a t i o s were printed out. The r e l a t i v e s p a t i a l dispersion of the mean, RSD, was calculated in the following subgroups: N = 50, 25, 17, i 0 , 7, 5, 3, 2 and 1 (N = number of the subregions). The v a r i a t i o n of RSD as a function of N was plotted out a n d t h e l i n e a r regression equation was f i t t e d to estimate the f r a c t a l dimension, D. The r e s u l t s showed a smaller p e r f u s i o n - t o - v e n t i l a t i o n heterogeneity in control subjects than in p a t i ents with v e n t i l a t i o n disorder. The corresponding f r a c t a l dimension, D was 1.15 and 1.24, respectively. I t is e a r l y to say i f i t is possible to evaluate changes in the dynamics of regional perfusion and v e n t i l a t i o n in c l i n i c a l use, but f r a c t a l models of many forms are i n t e r e s t i n g not only in anatomic but also in dynamic, functional understanding of b i o l o g ical phenomena.

curves. A measure of these parameters for each kidney were also obtained using the conventional

region-of-interest method (ROI), and used as our 'gold standard'. Results show the whole kidney transit time values were reasonably well correlated with all FADS methods, with the exception of apex-seeking. Values for parenchymal transit time obtained by FADS methods were generally higher and poorly correlated with values from ROI method. GFR values obtained by FADSwere higher and moderately correlated with values obtained by ROI method. These preliminary results have highlighted certain problem areas, and require further study in order to reach the goal of objective quantification of renal studies using FADS.

FP-4H1-4

FP-4H1-5

D.G. P a v e l J. Sychra, G. Kondos, E. Olea. U n i v e r s i t y of Illinois Hospital, Chicago, USA a n d Catholic U n i v e r s i t y , Santiago, Chile.

A S HOUSTON AND W B TINDALE

C L I N I C A L A P P L I C A T I O N OF C O M P U T E R G E N E R A T E D E X P E R T IMAGES (CGEI) IN T H E E V A L U A T I O N OF R E G I O N A L WALL MOTION A B N O R M A L I T Y (RWMA). We h a v e previously d e m o n s t r a t e d the feasibility of CGEI f o r the d i r e c t diagnosis of LV RWMA o r i g i n a t i n g f r o m c o n v e n t i o n a l r a d i o n u e l i d e g a t e d v e n t r i e u l o g r a m s (RGV) in optimal LAO, The classification a l g o r i t h m is based on 77 teaching images (TI) of normals a n d a b n o r m a l s a n d on the use of d i s c r i m i n a n t , regressior~ a n d n e u r a l n e t w o r k , analysis. The TI set was built b y consensus of 3-4 specialists who m a p p e d the RWMA d i s t r i b u t i o n based on clinical d a t a , biplane c o n t r a s t a n g i o g r a p h y , E C H O a n d a set of f u n c t i o n a l images o b t a i n e d f r o m R G V ( i n c l u d i n g phase a n d f a c t o r analysis). P r e d e f i n e d colors were assigned to each of 7 RWMA categories. The resulting 77 CGEI images (based on 16 parameters) were v e r y s a t i s f a c t o r y by pictorial a n d by statistical pixel by pixe[ analysis. A t this time the clinical usefulness of the CGEI is addressed by: 1) Using the "leave one out" (LOO) method on all images; 2) Entering new cases in the computer, while h a v i n g t h e m e v a l u a t e d i n d e p e n d e n t l y in same w a y as the original TI; 3) E v a l u a t i n g the cases w h i c h i n d i c a t e d s i g n i f i c a n t d i s c o r d a n c e (more t h a n one c a t e g o r y , a n d / o r m a j o r d i f f e r e n c e in a b n o r m a l ' s u r f a c e on LV map); 4) E v a l u a t i n g m i n o r discrepancies. Results: 1) 73/77 (95%) h a d excellent r e p r o d u c i b i l i t y before a n d a f t e r LOO; 2) new cases: 97% h a d an excellent correlation w i t h the specialist's map; 3) 5/77 were considered discordant: in 3/5 original TI b o u n d a r i e s were f o u n d to be too tight or large; in 1/5 LV hemibloek; in 1/5 no d e f i n i t e .explanation; 4) Minor discrepancies: 7/77 raised interesting questions a b o u t "gold standards". CGEI are clinically useful, robust, soon to be easily accessible a n d able to f u r t h e r r e f i n e / c h a l l e n g e c o n v e n t i o n a l methods.

560

ROYAL NAVAL HOSPITAL, HASLAR, GOSPORT, UK AND ROYAL HALLAMSHIRE HOSPITAL, SHEFFIELD, UK CATS: COMPUTER MEDICINE

AIDED

TEST

SELECTION

FOR

NUCLEAR

g report of the NRPB and RCR, cited in the national press, highlights the need for justification of tests which expose the patient to ionising radiation, A structured approach to the selection of tests could result in more appropriate investigations, a reduction in unnecessary radiation dose and significant resource savings. The aim of this work, which forms part of a UK project carried out within the COST B2 framework, is to develop an expert adviser for the selection of appropriate nuclear medicine investigations. The pilot study to develop a prototype expert system has been directed towards renal radionuclide procedures. The project was divided into 4 stages: knowledge e!ieitation, knowledge representation, system implementation and system testing. Knowledge elicitation was performed using questionnaires which were completed by 5 experts in different UK centres. The knowledge was represented in the form of a decision tree; responses from all 5 experts were included. The system has been implemented using a commercially available expert system shell, CRYSTAL4, and provides advice on tracers and tests, patient preparation, cautions and contraindications, and supplementary non-radioactive tests. Preliminary testing of the system by prospective users has highlighted specific areas for future development,

W e d n e s d a y , 4 S e p t e m b e r 1991

FP-4H1-6 TD Cradduck*, F Deconinck, A T o d d - P o k r o p e k and W o r k i n g Group #i, COST-B2 *University of W e s t e r n Ontariov London, Ont.,

INTERFILE

-

THE

CURRENT

Canada

FP-4H1-7 A. Todd-Pokropek and N. Margetic, Dept. of Medical Physics, University College London, UK.

STATUS

Interfile is a file format which has been d e v e l o p e d by W o r k i n g Group #i of the COST-B2 project and is based on the format p r o p o s e d in AAPM Report #i0 (Baxter et al, 1982). It is based on the concept of key-value pairs and descriptors have been e s t a b l i s h e d for all the r o u t i n e nuclear m e d i c i n e imaging modes. Additionally k e y - v a l u e pairs have been defined for curve data. A file folder format has been specified so that numerous studies can be retained under one header where the concept of inheritance allows redundant key-value pairs to be omitted. In the same context, studies, and their associated image data, may be collapsed under one header using the ~everse path to define key-value pairs. In this case, when the same key-value pair is defined more than once, the value closest to the image data is r e g a r d e d as germane. An e a r l i e r v e r s i o n of Interfile was p u b l i s h e d in 1989 (Cradduck et al, 1989). Since then additions have been made. The current version of Interfile is m a i n t a i n e d on a file server located at the U n i v e r s i t y of W e s t e r n O n t a r i o for access by electronic mail or anonymous ftpo The purpose of Interfile is that it be used to facilitate the transfer of software phantoms for use by the other w o r k i n g groups w i t h i n the COST-B2 project. The members of W o r k i n g Group #i are acknowledged for their c o n t r i b u t i o n to the development of Interfile. References: Baxter BS, H i t c h n e r LE, Maguire GQ Jr (eds): A standard format for digital image exchange, AAPM Report #i0. New York: Amer Inst Physics (1982) Cradduck TD, Bailey DL, Hutton BF, Deconinck F, B u s e m a n n - S o k o l e E, Bergmann H, Noelpp U: A standard protocol for the exchange of nuclear m e d i c i n e image files. Nucl Med Comm 10, 703-713 (1989)

FILE TRANSFER PROTOCOLS FOR USE IN NUCLEAR MEDICINE: LEAPFROG AND THE HARMON~Z.ATION OF THE ACR-NEMA AND INTERFtLE STANDARDS. With the increasing use of mu~ple computer systems and networks within nuclear medicine departments, and the need to be abis to ~'anster data between mamj' different (alien) computer systems, proper definitions of file b'anster protocols are essentiat. Two a~temal~vesets of definitions have been established: the ACR-NEMA protocol and Interfile (COST 132) file format definition. The aim of this s~udywas to create a program cxx:le-named LEAPFROG to translate between the two tile format defin~ons and, by so doing, to harmonise the two standards such that, from the point of view of a nuclear medicine user, either could be adopted without that user iffereiore being isolated from the alternative standard. Note that the ACWNEMA data format treated was that proposed (October t990) as a revision of ~ ACR-NEMA 3.0 standard to include many new nuclear medicine specific groups and elements. It was found that, while superficiaJly the form of the two standards is very different, the conversion of most standard ~ata types can be enabied by ctea~ng an appropriate Cam dictionary. Dynamic (in particular cardiac) studies can be manipulated by converting tPe proposed ACR/NEMA folder into the interfile dynamic sequence. However, SPECT data can only be bandied if uniformity correction and centre of rotation correction am assumed to have been porformed. List mode data has been excluded. However curves are readily t~anslatable, Some inconsistencies have been idsntified and reeommeedatiorts establishedfo¢" co.ect~ these p ~ . Maintenan~s of the d~.t~ dictJon~E ~sit~ ~;$~rq~ate torm.~ m~ttK>~% making the dictionary widely avaUable by electronic means, is be.eved to be assen~al.

FP-411-1

FP-411-2

K.Kletter, N.N~rnberger, T.Leitha, R. Dudczak I. Med. Dept.and Dept. of Urology, Univ. of Vienna, Austria

E.OZTORK*,Z.B[RCAN**, N.BUYAN**,H.BAYHAN*,E.HASANO(~LU",C.AKTOLUN', B.GUNALP*. *G~tihaneMilitary MedicalAcademy Nuclear MedicineDept. Ankara/TURKEY **Gazi University MedicalSchool, Pediatric Nephro]ogy Dept. Ankara/TURKEY

EVALUATION OF HYDRONEPHROSIS IN NEWBORNS BY DIURESIS RENOGRAPHY (DRG) - 5 YEARS OF EXPERIENCE The widespread use of ultrasound studies increased the detection rate of hydronephrosis in newborns. Consequently a functional test is needed to differentiate between nonobstructive dilatation and obstructive uropathy which may result in a loss of kidney function. The only minimal invasive DRG may serve as a screening test in this question. 62 newborns (age < 3 months) with 85 hydronephrotic kidneys underwent DRG using 1123 olH (O.55MBq/kgBW) or Tc99m MAG3 (2 MBq/kgBW). Follow up studies were performed in 35 newborns with a total of 124 investigations (2 - 6 studies/infant). Standard renography was done firstly; 20 min after tracer application 0.5mg/kgBW frusemide was administered iv. and washout was studied for further 15 min. Washout curves were analyzed quantitatively calculating the maximal elimination rate (Emax) for the tracer after frusemide. Results were classified as nonobstructive (Emax>14%/min), equivocal (Emax 6%/min - 14%/min) and obstructive (Ema×<6%/min). In 6 children with high graded reflux and hydronephrosis results were not interpretable in two. In 53(62%) hydronephrotic kidneys the postpartal DRG showed a nonobstructive result, in newborns with initially obstructive or equivocal Emax values follow up studies showed spontaneous desobstructien in 30% of cases. Desobstruction occured most frequently during the first 6 months of birth, but in a few cases an amelioration of renal outflow was observed up to an age of 2 years. However in 3 children with initial nonobstructive DRG a deterioration of renal outflow was seen in follow up studies during the first year of life. Our results indicate that a possible immaturity of kidney function is not an essential restriction in the application of DRG in newborns. This is evidenced by our high number of nonebstructive results (n = 52) even in premature born children (n = 3). In conclusion, the DRG is well suited to exclude obstruction in newborns with hydronephrosis. Newborns with hydronephrosis and obstructed urinary outflow show a surprisingly high rate of spontaneous desobstruction stressing the importance of DRG follow up studies. Therefore early surgery is not recommended in kidneys with obstruction but intact renal function.

CAN WE USE Tc-99m DMSA SCINTIGRAPHY AS A PRIMARY CRITERIA IN DIFFERANTIATION OF ACUTE UPPER AND LOWER URINARY TRACT INFECTION IN CHILDREN?

Since upper urinary tract infection (UTI) significantly contributes to the incidence of end-stage renal disease, accurate identification of the site and extent of infection may affect the duration and mede of treatment, and determine prognosis. In this prospective study, we investigated the value of renal cortical Tc-99m DMSA scintigraphy (DMSA-Sc) in both localizing acute UTI and follow-up of the treatment. We also compared the results of DMSA-Sc to those of renal sonography (US), intravenous urography (IVU) and voiding cystouretherography(VSU). 34 children with the diagnosis of acute UTI which was proved with culturing suprapubic aspiration material have been studied with planar or planar and SPECT DMSA-S~, US, IVU and VSU. After obtaining at least a 10-week-noninfectionperiod with treatment, 21 children were re-scanned, All of the abnormal DMSA-Scwere considered as upper UTI. Clinical localization were done according to symptoms and physical examination of children. The comparison of DMSA-Scwith US, IVU results and clinical localization is shown in the Table. DMSA~Sc

-- IVU i US CUNICALLOCALIZATION Abnormal_ Non'hal__Abnormal Normal UPPERLrn LOWERU'H

ABNORMAL

7

12

18

14

NORMAL

0

0

4

O

16 4

TOTAL

7

12

22

14

20

In control DMSA-Sc;2 showed complete, 8 signiticant, 8 partial recovery, but in 3 children no recovery were detected. Vesicoureteralreflux was detected in 3 patiens with VSU. In conclusion, Tc-99m DMSA renal cortical scintigraphy is a highly sensitive and reliable imaging modility for the detection, localization and follow-up of acute upper UTI, and it should be used as a first choice in imaging tree.

561

Wednesday, 4 September 1991

FP-411-3

FP-411-4

M. Isobe B.A. Khaw, H.W. Strauss, and E. Haber Cardiac Unit and Department of Nuclear Medicine, Massachusetts General Hospital, Boston, MA, USA

H. Rivera-Lur~, S. Sostre, H.H. Drew, H.N. Jr. and E.E. Camargo. The Johns Hopkins Institutions, Baltimore, MD, USA.

E A R L Y D E T E C T I O N OF K I D N E Y A L L O G R A F T R E J E C T I O N BY 123I L A B E L E D M O N O C L O N A L A N T I - M H C C L A S S II A N T I G E N A N T I B O D Y

M E A S U R I N G I%~qAL T U B U L A R F O N C T I O N ~

Induction of class II major histocompatibility complex (HHC) antigen precedes nephrocyte necrosis in kidney allograft rejection. To evaluate the detectability of early kidney rejection by 123I labeled anti-class II MHC antibody, 26 allografted mice (C3H/He [H2 k] donor, Balb/c [H2 d] recipient) and 5 isografted C3H/He mice were studied. YI7 monoclonal antibody (anti-IE k) was labeled with 1231. Planar scintigrams were acquired 16 hours after i.v. injection of labeled antibody (50 uCi) 1 to 19 days after transplantation. Graft/native kindey radioactivity ratio as determined by computer planimetry (G/N) in allografts was significantly elevated from the 4th day of transplantation and increased progressively with time until 6th day, then decreased gradually. G/N of 4 allografted mice at the 6th day was between 5.7 and 6.8. Rejected allografts with focal cell infiltrates as determined by histopathology could be identified by the scintigraphy. Nephrocyte necrosis due to rejection accounted for the late reduction of G/N. Isografts and allografts (Balb/c donor, C3H/He recipient) did not show any increase in G/N (1.1±0.2). Four mice with high G/N showed marked reduction of G/N after the treatment with anti-CD3 antibody and cyclosporine (before 5.2±1.3, 2 weeks 2.6~0.6, 4 weeks 1.6±0.8). Two weeks after the cessation of treatment two mice showed a re-elevation of G/N (5.7 and 4.3) reflecting a recurrence of rejection. Thus, immunoscintigraphy using 123I labeled anti-class II MHC antibody is useful in the early detection and follow-up of kindey transplant rejection.

Renal water ~ r p t i o n is a complex tubular function. We have developed a technique to measure water reabsorption using [99m]Tc-DTPA. As DYPA is neither reabsorbed nor secreted in the tubules, any difference in DI~A concentz-ation between filtered plasm~ and urine must be due to tubular water reabsorption. After i.v. injection of 3.7 MBq of [99m]Tc-DI~PA (DTPA), two blood saai01es and a urine oollection between 60 and 90 minutes were obtained. Urine and ~ DTPA concentration in c ~ m l / M B q and urine volumes were measured to calculate the following parameters: total DTPA excretion, fraction of water reabsorbed (FWR), and urine/semen DTPA concentration ratio (U/S), which reflects the number of times the filtrate has been concentrated. We employed the met.hod in 618 patients (pts) with GFR ranging frmm 2 - 170 a~I/min. Total DTPA excretion decreased linearly with the GFR. The water reabsorptive capacity also decreased but not linearly. The most striking changes occurred with GFR below 20 ml/min where FWR of 0.18 could be seen. In pts with normal GFR, the FWR ranged from 0.92 - 0.99 for urine volumes of 1-8 ml/min and only decreased to 0.84 in extreme hydration states. Urine DTPA concentration was much lower in pts with renal insufficiency probably due to decreased FWR which led to dilution of the already reduced urine DTPA excretion. Specific gravity (SG) in 66 patients correlated poorly with 9WR and U/S probably because SG does not reflect the reabsorptive function of the entire tubular system. This new technique is a promising tool for the simultaneous measurement of gl(~l~_rular and tubular function.

FP-411-5

FP-411-6

C. Van Nerom, M. Waer, C. Claeys, M. De Roo, A. Verbruggen Departments of Nuclear Medicine and Nephrology, Univ. Hosp. Gasthuisberg, K.U.Leuven, Belgium. CLINICAL EVALUATION OF 99roTe L,L-EC AS AN ALTERNATIVE FOR 99mTc MAG3 IN RENAL TRANSPLANT PATIENTS. 99mTc-L,L-ethylenedicysteine (99mTc-L,L-EC, ~ is a new stable diimine dithiol tetradentate ligand based 99mTccomplex that easily can be prepared from a labelling kit at room temperature. In mice and baboon I approaches 131I-hippuran ( ~ more closely than 99mTc-MAG3 (L!I). Our first results with I in human volunteers have revealed its excellentrenal excretion .characteristics and its potential as an appropriate and more practical renal function agent than IH. We have now compared ! and Ill in 6 kidney transplant patients, using II as internal biological standard. Approval of the local Ethical Committee was obtained. Renal transplant patients with slightly reduced renal function were selected on basis of biochemical and clinical parameters. Informed consent was first acquired. 37 MBq of HPLC-purified I or III was coinjected with 3.7 MBq II. Sequential imaging studies were performed using a LFOV camera equipped -with a high sensitive parallel collimator. AP-images of the kidney and bladder region of the patient in supine position were acquired during-30 rain. Renograms of I and Eli in the same patient were very similar. Plasma protein binding of I was much lower and its distribution volume larger than that of Ill, as it was also the case in normal volunteers. One hour plasma clearance of _I was slightly higher than that of Ill in most but not all patients and amounted to 60-70% of the hippuran value. Urinary excretion of both 99rnTc compounds was comparable. It is concluded that 99mTc-L,L-EC iS an excellent tracer agent for renal function studies in kidney transplant patients. It has the advantage of its high purity ( > 98%), stability ( > 8 h) and ease of preparation (RT). Further studies are required to reveal its value in patients with impaired renal function.

562

Wagner, Medical

[99m]Tc-DTPA.

W. Burchert, *J. Sch~ffer, *J. FI6ge, P. Gielow, *K.-M. Koch, H. Hundeshagen. Dep. Nuclear Medicine and *Nephrology Medical School Hannover, Germany I - 131 - B E T A - 2 - M I C R O G L O B U L I N : A N E W T R A C E R FOR IMAGING OF DIALYSIS - RELATED AMYLOID (AB-AMYLOID) DEPOSITS

The dialysis-related amyloidosis is a serious complication in long-term hemodialysis patients. Its prevalence is estimated to vary from 30 to 100%. Hitherto the diagnosis mainly has been made on clinical (e.g. carpal tunnel syndrome) and radiological grounds (juxta-articular radiolucent Cystic bone lesions) or - more specific - by biopsy. As a new sensitive, specific and non - invasive diagnostic procedure 1-131-Beta-2-Microgobulin scans (74 MBq) were acquired 72-96 hrs after application in 42 pts. on chronic hemodialysis. 23 pts. showed tracer accumulation in the areas of shoulder, hip, knee or wrist. Pts., who were on dialysis for less than 5 years had no uptake, those with 5-10 years dialysis had 63% positive scans and those for more than 15 years on dialysis had 100% positive scans, Compared with clinical/radiological findings the scintigraphy had more positive results. 10 days p:i. one patient died caused by cerebal bleeding. Tissue obtained by autopsy showed amyloid fibrils with a strong uptake of labelled microglobulin. Tissue samples of three other pts. obtained by biopsy/surgery had specific accumulation of labelled microglobunn in different areas of amyloid. In summary the 1-131-beta-2-microglobulin-scinSgraphy may be a new non-invasive diagnostic method for practical use in the diagnosis ol dialysis-related amyloidosis, which is superior to the combined clinical and radiological method.

Wednesday, 4 Septembe r 1991

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K. Tatsch, J. Schwarz, W.H. Oertel, C.-M. Kirsch

DOPAMINE RECEPTORS IN PARKINSON'S DISEASE S.Wenger, T.BrOcke,I.Podreka,S.Asenbaum,P.Angelberger Neurologische univ.Klieik Wien, Forschungszentrum Seibersdorf

Departments of Radiology and Neurology, Klinikum Grosshadern, University of Munich, Munich, FRG 1-123 IBZM SPECT FOR IMAGING DOPAMINE D2 RECEPTORS IN IDIOPATHIC PARKINSON SYNDROME, PARKINSONIAN-LIKE SYNDROMES AND WILSON'S DISEASE

The assessment of dopamine D2 receptor density, occupancy or blockage by 1-123 IBZM SPECT may potentially be useful in a variety of neurologic disorders. This study investigates striatal IBZM-binding in idiopathic parkinson syndrome (IPS), parkinsonian-like syndromes (PS) and Wilson's disease (WD). Sixty patients were studied (controls: n=8, IPS: n=18, PS: o=24, WD: n=10) with their diagnosis established clinically, by pos. (IPS)/neg. (PS) response to long term L-dopa or biochemically (WD). Most pts (n=47) were untreated, 9 were off dopaminergie drugs for >6 months, 4 for >2 weeks. SPECT was performed 2h after appl. of 185 MBq 1-123 IBZM. For semiquant, evaluation basal ganglia/frontal cortex (BG/FC) ratios were calculated after attenuation correction. In 18/18 IPS-pts striatal accumulation of IBZM was normal, in 20/24 PS-pts it was markedly reduced. 4/24 PS-pts had normal SPECT findings, though no improvement on L-dopa was observed. In 8 pts with WD and presence of neurologic symptoms IBZM-binding was significantly decreased, 2 asymptomatic pts with WD showed normal SPECT studies. BG/FC ratio

controls 1.55_+0.05

IPS 1.51_+0.05 n.s.

PS 1.35+0.11 p<0.001

The therapeutic efficiency of dopaminergic drugs in Parkinson's disease depends on dopaminergic r e c e p t o r s . Depending on their action on adenylate cyclase they a r e classified as DI o r D2 receptors. The dopamJne D2 receptors can be visualized in the living human brain by SPECT using a selective D2 antagonJst(Iodobenzamide). We investigated striatal D2-reeeptor densities in 19 controls, 5o parkinsonian patients and 4 patients suffering from multi-system-atrophy. D2 receptor binding was expressed as ratio between mean striatal countrate and latero-fronta] cortical countrate. T h e r e was a significant decline of this ratio with increasing age in both controls and parkinsonian patients. Ratios of L-Dopa treatedbut n o t of untreated parkinsonia~ patients w e r e decreased compared to age matched controls. We found no correlation between the clinical stage and Iodobenzamide binding.Patients with unilateral symptomatology tended to show an increase of striatal D2 receptor binding contralateral to the affected side. Patientslwith multi-system-atrophy can be differentiated from patients with idiopathic ParkJnson's disease by a marked decrease of D2 binding.

WD 1.35+0.17 p<0.001

The data presented suggest IBZM SPECT being potentially useful for discriminating patients with IPS from those with PS of other origin (sensitivity:100%; specificity:83%) irrespective of their clinical response to (long-term) dopaminergic therapy. In WD changes in striatal IBZM-binding seem to correlate with the presence of neurologic symptoms.

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DC COSTA MS GEORGE, PJ ELL, NPLG VERHOEFF, MM ROBERTSON. Institute of Nuclear Medicine and Department of Psychiatry, UCMSM, Institute of Neurology, NHND, London, UK, and Cygne BV, The Netherlands.

HA RING*. MR TRIMBLE*, DC COSTA¶, NPLG VERHOEFFt, PJ ELL¶. *Institute of Neurology, NHND, London, UK. ¶Institute of Nuclear Medicine, UCMSM, London, UK. tCygne BV, Technical University, Eidhoven, The Netherlands.

D2 DOPAMINE RECEPTOR STUDIES IN PATIENTS WITH GILLES DE LA TOURETI'E SYNDROME.

EFFECTS OF VIGABATRIN ON STRIATAL DOPAMINE RECEPTORS.

It is thought that in patients with Gilles de la Tourette Syndrome (GTS) doparnine overactivity or supersensitivity leads to the tics seen in this disease. It has been suggested that D2 dopamine receptors play a role in the pathogenesis of GTS. Abnormalities of dopaminergic markers have been found in 'post-mortem striatal specimens of patients with this condition. In order to investigate whether this dopamine dysregulation might be studied in vivo we performed single slice dynamic single photon emission tomography with 123I-iodobenzamide (IBZM) in 15 GTS patients, 7 of them drug-naive in comparison with 6 normal controls. All the studies were carried out with the approval of the local Ethical Committee and Administration of Radioactive Substances Advisory Committee (ARSAC).

Vigabatrin is a new antiepileptic drug. Its use has been associated with the sporadic development of a schizophrenia-like psychosis. In this study we investigated the hypothesis that this side-effect was due to an effect of the drug on dopamine receptors. Six epileptic patients underwent 2 SPET scans; the ftrst prior to starting vigabatrin and the second after one month of treatment. In every patient both scans were performed on the SME 810 Brain Tomograph. At the start o f each scan the subject received an intravenous injection of 5 mCi (185 MBq) of 123I-iodobenzamide (123I-IBZM). Twenty images at the level of the basal ganglia (OM line + 30 to 40 ram) were obtained over the 2 hours post-injection. Each was submitted to a region of interest analysis. Ratios of specific to non-specific binding during the scan were calculated for each patient when "ON" and "OFF" treatment.

5 mCi (185 MBq) of 123I-IBZM was administered intravenously and dynamic SPET (5 minutes slices) performed at the level of the basal ganglia (OM line + 30 to 40 mm) for 1 to 2 hours. Specific radioactivity in basal ganglia was calculated by obtaining basal ganglia to frontal cortex ratios (BG/FC) at each time point from 5 minutes to 2 hours post-injection (p.i.).

It was found in the on-treatment scans that overall, using paired Student's t tests, there was a significant decrease in specific binding to striatal D2 receptors in the left basal ganglia on 5 consecutive time points (p
At 30 minutes p.i. the BG/FC ratio was 1.52 for normal controls and 1.32 for unmedicated GTS (p = 0.012). After this time point there was a clear and statistically significant (p = 0.025) separation between the time-activity curves for controls and GTS.

It is concluded that this change represents receptor down-regulation consequent upon vigabatrin-induced increased dopamine release. This effect may be related to the development of psychosis.

These data demonstrate that unmedicated GTS patients have lower binding capacity of 123I-IBZM to the basal ganglia than controls. This suggests a higher resting dopaminergic state in GTS with down-regulated D2 receptors in the basal ganglia.

This study was passed by local ethical and regulatory authorities.

563

Wednesday, 4 September 1991

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N. P. L.G. Verhoeff, E. ~. ~ Royen, D.H. Linszen, {5. nuYser, ana ~i Bobeld/j~. De p a r ~ e n t s o f Nuclear Meclicine and Psychiatry, Acaeemic .Me~.'cal Centre~ Amsterdam, and Cygne B. V., Technical Un/versity Einunoven, The Netherlands.

Wagner-Jauregg-Krankenhaus Wagner-Jauregg-Weg 15 A-4o2o Linz, Austria

IN VIVO DOPAMINE D2-RECEPTOR IMAGING WITH 1-123 IODOBENZAMIDE SPECT USING A LC~G-BORE COLLIMATOR

1-123 (S)-(-)-2-hydroxy-3-iodo-6-methoxy-N[ (lethyl-2-pyrrolidinyl~mg. ,thyl]Tbenzamide II-123 IBZM, spec. act. 3000-3300 Ci/mmo-), a promiszng D2-receptor imaging agent for SPECT, ~ receh tly b@en syntheszzed Dy some oz us. AS r/%e Long-Pore COLllma~or F~qS a better resolution a/~ qives better contrast of small structures the general purpose collimator, this typ@ of COLLimator was usea to increase v_ne image ~q~_~ity of the basal ganglia (BG). SPECT was performed in 5 heal_thy volunteers (~ men, 2 w o ~ D ; 22-25 years) and in 3 patients wir/1 schizopn_re_nia under clinical doses of ne.uroleptics (3 men; 2 1 - 2 5 years~ pimozide i0 ~ and 12 ua./iy, ana Dromoperiaol D m g aai±y~ wiv21 a ,GE MAx± rotating gan~a-camera after i ~ e e ~ l o n tp. i. ) of 5. mCi , I7123 IBZ~ From 90-120 mln p.z rme camera nead turnea CLockwise (CW), whereas xrom 120-150 minD. i. the head turned counter-clockwise (CCW). Ratios of-radioactivity [counts/pixeL) of ROIs were calculated with the BG in ~ne numei-ator and the cerebellum (CB), occipital cortex (OC), po6_terior termporal c.ortex (%POC[, parletal cortex (PC), ~und frontal cortex (~5) in tne denbnfinator. Results (mean -+ SD): Time p.i. 90-120 min Group Volunteers Patients

120-150 min Volunteers Patients

BG/CB BG/CO ~ I ~

2. 40-+0. 22 2. 44-+0. 33 1.98+-0.21 I. 85-+0. 16 i. 93+-0.06

2.05-+0.17 !. 95-+0. 26 i. 94-+0.18 ~[ 84-+0. 21 97-+0. 16

I. 41-+0. 09 I. 32-+0. 21 1.27-+0.23 i. 30+-0. 13 i. 27-+0. 14

i. 41-+0. 25 1.66-+0.46 1.64+0.38 i. 27-+0.04 i. 32-+0. 22

NO difference in left/right ratios of the basal genglia was onse.ry.ea wi~n eisner CW or CCW rQtatior~ The. longpore. COLLimator provided better quali~y images r/±an elf-Her a szan~no±e or a med/um energy ~ollilhator. The di.'ffering ratios between volunteers ~-nd patients conzirm the dopamlne D2-receptor spaoilicity of 1-123 IBZ~i

Deisenhammer E., Brucker B., Schubiger P.A., Diem R.

BRAIN SPECT USING A BENZODIAZEPINE(BZD)-RECEPTOR LIGAND (IOMAZENIL) ~cecific receptors are thought to mediate the various pharmacological effects orBS) administered for therapeutic purposes. These receptors may either be changed reversibly in hepatic encephalopathy and seizures or altered irreversibly in degenerative disorders.BZD receptors were imaged by SPECT with Iomazenil(I). After i.v. injection, the initial regional uptake in the brain tissue depends on regional blood flow. Later, regional distribution of BZD receptors. A S P E C T study done within a period of 15 minutes post i.v.injection of I therefore permits tomographic imaging of regional blood flow in analogy to other CBF markers. A delayed SPECT scan performed 12o minutes post injection shows the distribution of receptors. This justifies using I for the imaging of rCBF and doing a delayed scan for the imaging of receptors. The tracer was used for diagnostic purposes in different neurological diseases including epilepsy. A total of 72 patients were investigated; in 56 of them, a SPECT study using a different CBF marker was done within a few days. The SPECT of hypoactive lesions indue various diseases obtained by the initial study with It he delayed study with I and the study with another CBF marker showed no essential differences. So far SPECT shales in various diseases have not furnished any additional information beyond the results obtained with other CBF markers.

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Chr. Reiners, H.Peters, C.Fischer, H.Schleusener. Clinic for Nuclear Medicine, University of Essen and Clinic for Internal Medicine, Free University of Berlin, F.R.G.

U. F. Willemsen, C. R. Pickardt*, T. Kreisig, P. Knesewitsch. Department of Radiology, Division of Nuclear Medicine, Department of Internal Medicine Innenstadt*, University of Munich.

RESULTS OF A GERMAN MULTICENTRIC STUDY ON TREATMENT OF GRAVES' HYPERTHYROIDISM WITH A STANDARD ACTIVITY OF 550 MBQ VS AN INDIVIDUALLY CALCULATED DOSE 100 GY

THYROID ABLATION WITH A 300 GY ABSORBED DOSE IN

According to the literature, in areas with sufficient iodine supply a 90% cure rate of Graves' hyperthyroidism may be achieved with a fixed therapeutic activity of 550 MBq 1-131 as well as with an individually calculated energy dose to the thyr6id of 100 Gy. We compared the effectivity of these two regimens under the condition of WHO grade III iodine deficiency in a prospective, randomized German multicenter study. 230 patients of 9 centers with Graves' disease were randomized. 1-131 treatment was carried out in 214 patients, complete follow-up data are available for 210 cases. 95 patients were given 550 MBq 1-131 ("Standard"), 105 patients received an activity of 1-131 calculated b'y the formula: activity (MBq) = 22.6 *xI00 (Gy) x thyroid volume (ml) -[ max.uptake (%) -" effective halftime (d) ("Individual"). Clinical autcome was determined 6 months after radioiodine treatment. Succes was defined as euthyroidism (normal T4 and T3) and hypothyroidism (elevated TSH). The succes rates in relation to the thyroid volume were (with 95% confidence intervals): volume <= 30 ml 31-49 ml >= 50 ml total

34/39 13/26 14/30 61/105

Individual (69%, 56-82%) (50%, 30-70%) (58%, 28-66%) (58%, 48-67%)

44/46 16/27 7/22 69/95

Standard (96%, 40-99%) (67%, 46-84%) (32%, 14-55%) (73%, 63-81%)

Both regimens appear not to be sufficient under the conditions of iodine deficiency. It seems to be advisable to treat patients with higher individual doses of 150 200 Gy.

564

GRAVES" DISEASE. Recurrent hyperthyreoidism due to Graves" disease may require an a b l a t i v e radioiodine therapy accepting the development of hypothyroidism. The administered a c t i v i t y has to be determined by t h y r o i d volume and radioiodine k i n e t i c s . Since 1985 28 patients with recurrent severe hyperthyroidism (23 females, 5 males, 52 - 13 years) were treated by a b l a t i v e radioiodine therapy with an i n t r a t h y r o i d a l absorbed dose of 300 Gy. Thyroid volume was determined by ultrasound; max. storage and e f f e c t i v e h a l f - t i m e by radioiodine t e s t . The applied a c t i v i t y ranged from 240 MBq to 3120 MBq (median 970 MBq). Post-therapy controls were performed a f t e r 3 months (m) and t h e r e a f t e r in 3-6 months i n t e r v a l s . Manifest hyperthyroidism was eliminated in 89 % a f t e r 3 m, 93 % a f t e r 7 m and 100 % a f t e r 10 m. One patient had l a t e n t hyperthyroidism a f t e r 10 m without needing a n t i t h y r o i d a ! drugs. The r a t e of hypothyroidism was 57 % a f t e r 3 m, 71% a f t e r 7 m and 71% a f t e r 12 m. The latency period of developping hypothyroidism was n e i t h e r dependent on the app]ied a c t i v i t y nor on pre-therapeutic T S l - t i t e r . Posttherapeutic t i t e r were p o s i t i v e in 14/16 patients. Conclusion: Radioiodine therapy with a 300 Gy absorbed dose causes ablation of the t h y r o i d . In contrast to a therapy with standard a c t i v i t i e s the i n d i v i d u a l l y required a c t i v i t y is determined, thus reducing unnecessary r a d i a t i o n exposure. Hyperthyroidism is r e l i a b l y eliminated with a high rate of hypothyroidism. Ablative therapy with a 300 Gy absorbed dose should be r e s t r i c t e d to recurrent cases.

Wednesday, 4 September 1991

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A.Bockisch, B. Briele, B. Overbeck, A. Hotze, T. Jamitzky, R. Derwanz, H.J. Biersack. Kliniken ffir Nuklearmedizin, Universit~it Bonn & Mainz, Germany

A Karwowska Czlaskiewicz, J.Makarewicz. A.Rutkowski, Department of Nuclear Diagnostics and Therapy, M.Curie-Sklodowska Hospital. Parzeczewska 35, Zgierz 95-100. POLAND

OPTIMIZED DOSE PLANNING FOR RADIOIODIDE THERAPY (RIT) OF BENIGN THYROID DISEASE.

THE PROBLEM OF ISOTOPE DOSAGE CHOICE IN GRAVES DISEASE WITH QUICK IODINE TURNOVER

The two main problems in R1T are how to determine the activity needed to reach the desired focal dose and how do the dynamics of a small test activity (TEA) correlate with that of the therapeutic activity (ThA). Patients and methods: A prospective study in 246 patients suffering from benign thyroid diseases compared the focal dose predicted from the dynamics of a small TeA (7 MBq 1-131) with the actually deposed dose by a ThA (144-1440 Mbq). The thyroidal 1-131-uptake was measured 8, 24, 32, 48, 72, 120, and 192 h after oral administration either of the TeA or the ThA. From these data the cumulated focal dose was calculated using a computer code. 100 Sv (Grave's disease) to 200 Sv (toxic adenoma) were applied. Results: 1. The thyroidal 1-131 dynamics are different for ThA compared with TeA, which results in art approximate 20% underdosage for patients without or with unchanged thyroid depressants during test and therapy. 2, Changing the dose of thyroid depressants disturbs any correlation. 3. The necessary therapeutic activity can be predicted using only one late uptake e.g. 96 or 192 h. The constants of the following formula were fitted to the testdata of all patients:

Calculation of a radioactive iodine dose in therapy of hyperthyroidism is based on estimating a thyroid weight and iodine uptake measurment. The estimated dose in therapy of 14 patients with Graves disease (30-50g thyroid gland weight, 65-78% T24 ~s=I uptake) carried out in our department appeared to be ineffective. The therapy required the following dosage every two or three month what mounted up 25-32mCi xsxI in every case. Thiama~ole initial treatment neither changed shape of the ms~I uptake curve nor reduced the high serum antibody level. Our dosage correction was estimated by integration the z3~I uptake curve to calculate the absorbed dose. The corrected dose appeared to be significantly higher than the calculated one based on the 24- and 48- hour uptake. We suggest that presented corrected method more precisely defines required absorbed dose. It is particulary important in therapy of Graves disease in patients with quick x ~ I turnover and high levels of antibodies.

activity [ M B q ] = const(t) . m a s s [g] . dose [Sv] / uptake [%1

const(96h)=2.46; const(192h)=l.62; standard deviation: 8%. Conclusions: The focal dose in radioiodide therapy of benign thyroid disease may be predicted from a single (late) uptake measurement with sufficient accuracy. Radiation effects change the dynamics of therapeutic 1-131 activities in a disease dependent way so that about 20 % underdosage results, for which an easy correction may be performed.

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Marie-Luise Sautter-Bihl, ~G.Herbold. HG Heinze. *H.Bihl Dept of Hadiooncology & Nuclear Medicine, Staedt. Klinikam Karlsruhe, *Katharinenhospital Stuttgart, FRG

B.Briele,A.Hotze,J.Kropp,F.Grunwald H.J.Biersack Department University

DIFFERENTIATED THYROID CARCINOMA. IS RADIOIODINE THERAPY ALONE SUFFICIENT IN CASE OF HIGH RISK FOR CERVICAL LYMPH NODEMETASTASES ? SOME DOSIMETRIC CONSIDERATIONS WITH MONTE CARLO TECHNIQUES.Indication for postoperative external radiation of diff. thyroid cancer has remained an issue of controversial discussion and is generally restricted to those cases where local tumor control by 1-151 therapy alone seems doubtful. This may he the case when 13anphnode metastases are present or occult micrometastasis are suspected, as the B-radiation caused by the incorporated 1-151 may be deposited partly outside the tumor. Thls problem of dose distribution is analysed in a computer simulation model by Monte Carlo(MC) techniques (program system: Electron-Gamma-Shower Code Version 4) where tumors are tissue equivalent spheres of various size (r=20um-2cm). Homogenous 1-151 distribution in the whole tumor volume(a) is analysed as well as peripheral deposition confined to the tumor surface(b). The results of the MC-simulation are expressed in terms of both the ratio of intra/extratumoral dose deposition and the 5-dimensional intratumoral dose patterns. Results: Assuming same values of 1-151/g tumor, complete (i.e.>98%) intratumoral dose deposition is only atteined when tumor diameter becomes >2.0 ran. In tumors of r=0.5mm or less, the percentage of the total dose deposited inside the tumor rapidly decreases, r=20um: 4.1%(a) and 0.9%(b). respectively. Furthermore. extensive dose inhomogeneities appear in tumors of these sizes. Conclusions: These data suggest that in local lymphnode (micro-)metastases tumoricidal radiation doses may not necessarily be achievable by 1-131 therapy alone. Postoperative external beam radiation should be taken into account in the above mentioned clinical situations if maximal tumor cell killing is intended.

,

of N u c l e a r M e d i c i n e , Bonn, Bonn, F R G

FOLLOW-UP OF DIFFERENTIATED THYROID CARCINOMA USING A NEW THYROGLOBULIN-ASSAYAND DELAYED POST THERAPY 1-131 IMAGING.

T h i s s t u d y w a s u n d e r t a k e n to c l a r i f y w h e t h e r in p a t . w i t h i n c r e a s e d Tg conc. and n e g a t i v e p o s t therapy scan (PTS) t h e s e n s i t i v i t y for t h e d e t e c t i o n of m e t a s t a s e s c o u l d be i m p r o v e d b y d e l a y e d 1 - 1 3 1 - s c a n s ( D S ) . M e t h o d s : a) D S : I n addition to the PTS-protocol (administered activity: 3700 MBq), s c a n s w e r e p e r f o r m e d at 96 a n d 12Oh. b ) h T g conc. w a s d e t e r m i n e d u s i n g a s u p e r s e n s i t i v e a s s a y (sens.< ing/ml). Also, r e c o v e r y t e s t s w e r e p e r f o r m e d a n d a n t i b o d i e s (TAK, MAK) to h T g w e r e measured. Tg w a s c o n s i d e r e d positive, w h e n conc. w a s >2 ng/ml, t h e r e c o v e r y normal, and there w e r e no antibodies, c) A t u m o r / b a c k g r o u n d - r a t i o a n d d) a s c a n s c o r e w e r e e s t a b l i s h e d for PTS a n d DS. S c o r e i: c o m p l e t e l y n o r m a l a f t e r 72h, 2: q u e s t i o n a b l e f i n d i n g s at 72h, 3: c l e a r l y p o s i t i v e f i n d i n g s at 72h. Pat.: n = 2 0 ; f e m a l e : 15, male: 5; age: 25-71y. D i a g n o s e s : p a p i l l a r y : 12, f o l l i c u l a r : 8. R e s u l t s : Pat. w i t h h T g pos.: 20 ( 2,7 - 757 n g / ml). P T S s c o r e i: n=4, 2 h a d s c o r e 3 in DS; PTS s c o r e 2~ n=12, 4 h a d s c o r e 3 in DS; PTS s c o r e 3: n=4. In t h e s e pat. w i t h m e t a s t a s e s in o n e a d d i t i o n a l met. w e r e d e t e c t a b l e on DS. Conclusions: l. T h i s s t u d y s h o w e d m o r e i n f o r m a t i o n b y DS c o m p a r e d to PTS in 2 0 - 3 0 % of pat. 2 . T h e n e w s u p e r s e n s i t i v e Tg a s s a y o b v i o u s l y allows e a r l i e r d e t e c t i o n of meta. or relapse. 3 . N e g a t i v e T g does not exclude meta.or relapse. 4.The consequences f r o m pos. DS: p o s s i b l e o p e r a t i v e access, b e t t e r staging.

565

Wednesday, 4 September 1991

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Z.X. He. J.C. M a u b l a n t , J. Darcourt, J. Benoliel, F. Lapalus, A. Veyre. Centre A. Lacassagne, Nice & Centre J. Perrin, C l e r m o n t Ferrand, France & Cardiovascular Institute, CAMS, China

University of Ulm Departement of Nnklear Medicine

A PROGRAM FOR AUTOMATIC REORIENTATION OF LEFT VENTRICULAR (LV) L O N G A X I S IN TL-201 SPECT

R W e l l e r , M Clausen,K KSnig,E Henze,WE A d a m

A new M e t h o d for Ejection Fraction (EF) Calculation in R a d i o n n u c l i d e - V e n t r i c u l o g r a p h y (RNV)

Reorientation of L V long axis is a mandatory step for short axis display of T1-201 tomograms. W e developed an automatic program for reorientation of transaxial t o m o g r a m s (TT) reconstructed by filtered backprojection. A reference image is created by summation of three contiguous midventricular slices, zoomed by a factor of 2.0, and rotated by +67.5 °. The LV apical limit is defined at the endocardial portion of apex and the basal limit at L V base. The linear profiles between these two limits are created line by line. On each of these, the two peaks represent the septal and lateral walls, and the point with the m i n i m u m counts between the two peaks is detected. The set of points with m i n i m u m counts are fitted by a straight line representing the LV long axis, and the reference image is rotated. T h e above procedure is repeated until the fitted line is c o m p l e t e l y superimposed on the Y-axis. The ] T are rotated and a similar algorithm is applied to the sagittal slices reconstructed from the rotated TT. This program allows for reconstruction of myocardial oblique angle tomography without manual selection of L V long axis, and improves the accuracy and reproducibility of quantitative analysis.

The precision of the calculation of EF in RNV depends mainly on two factors: The definition of correct ventricle borders and the observation of the correct background value. Purpose of the study is the design of an algorzthm that will not require any background or endsystolic region definition. At the beginning endsystolic ROI coincides with the enddiastolic ROI. By reducing the endsystolic region step by step in an onionskin manner, several intermediate variables (IV) where calculated, according to the EF-Formula without background consideration. The IV values show a linear correlation to the enddia.-endsyst area ratio (AR) EFT + R R BG IV i. . . . . . . . . . . . . . * AR i / R .... 1 + R 1 + R EDC This dependence can be described by a linear regression fit. From the straight line parameters (intercept and slope), the back@round and the true ejection fraction (EFT) wzthout any background-contamination can be evaluated mathematically. The error bandwith is determined, not onl[ taking in account the statistical properties of the count values, but also the relevance of the calculated background for the evaluated heart region. For a group of normal patients(n=20), the left ventricle ejection fraction (EFT) correlates with our standard EF with r= .944, resulting in a LVEF of 68.2 % ± 10.3 and in a right ventricle ejection fraction of 55.6 % + 6.9. In conclusion, a new algorithm is introduced that will compensate, m a t h e m a t i c a l l ? proven, for general problems in nuclear medzcine: the difficult region definition and the undesired backqround counts.

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L. yan Elmbt, A. Keyeux, A. Robert, Centre de M4decine Nud~aire, University of Louvaln School, Brussels, Belgium.

M. Gy6n~Ssi, F.D. Maul, R. Standke, H. Klepzig, T. BaewChristow, D. Mildenberger, M. Kaltenbach, G. H6r. Division of Nuclear Medicine and Cardiology, J. W. Goethe University Medical Centre, Frankfurt/Main, F R G

AUTOMATED CONTOUR DETERMINATION IN CEREBRAL

AN ALTERNATIVE AUTOMATIC METHOD FOR 3DIMENSIONAL QUANTIFICATION OF MYOCARDIAL ISCHEMIA AND SCAR UTILIZING TC-99M SESTAMIBI

SPECT

Photon absorption inside the head occurs as a major drawback on the way towards quantitation. Considering the comfort of the patient, attenuation correction by calculation was preferred to correction by transmission tomography d~ta for routine clinical practice. In case of the head, one can approximate the absorption by two attenuation coefficients, one for the brain and the other for the crane. However this requires a method to determine accurately both head and brain contours. The algorithm of T. Tomitani used already in PET has been implemented in case of SPECT. It was preferred among others methods, because of its simplicity and its rapidity. The algorithm is based on the detection of the borders of the sinogramme and is therefore independent on the reconstruction method. The validation was firstly performed on a cylindrical phantom modeling the head. Identity,of the contour of the SPECT picture and circumference of the phantom was found for a threshold located at 35 % of the maximum value of each sinogramme. With this in mind, the procedure was i~pplied to SPECT data on normal volunteers. The contours obtained were compared to those obtained in the corresponding CT-scan transverse section on the same subject. Measurements show that the variation is negligible on the length of the contours as well as on the area, which are similar in normal subjects with a high probability (p < 0.05) based on the Spearman R correlation test. Pathological conditions can decrease this probability by modifying the shape of the contour. This happens when a defect located at the border is extended in size and when its activity lies below the detection threshold. However this drawback is satisfactorily overcome by requiring that the contour must be symmetrical.

566

Based on the proved planar sectorial myocardial scintigraphy this method has been extended to three dimensions. A baslcal precondition is an automatic method yielding in precise defined short-axis slices. Myocardial SPECT utilizing Sestamibi was done according to the one-day protocol (exercise-rest). 32 projections were reconstructed to 64 slices using filtered back projection (ramp) and 3-dimensional filtering (Wiener). The reorientated short-axis slices were automatically summed to 6 slices of equal thickness, covering the distance between apex and valve plane. Each of the four inner slices was transformed to polar coordinate and analyzed in terms of relative radial uptake profiles within 18 equiangular sectors. Ischemia was quantitated by three different parameters: 1. maximal uptake difference between exercise and rest 2. integral of all significant uptake differences 3. number of sectors showing significant differences The integral proved to be the b e s t p a r a m e t e r to differentiate significant ischemia in 50 patients (pts). Scar was quantitated by 3 similar parameters using the difference between resting study and normal values. Reproducibility was tested in 12 pts which were processed 10 times resulting in a variation coefficient < 1%. Sensitivity and specificity of this method in the diagnosis of ischemia was 87 resp. 86%, and in the diagnosis of scars 84 resp. 93%. Out of these 50 pts global ejection fraction (GEF) at rest was determined in 28 pts. The correlation between perfusion defect at rest and G E F was r = 0.7. We conclude, that quantitative myocardial SPECT using Tc99m Sestamibi is highly reproducible method and an optimal tool in the diagnosis and therapy control of CHD.

Wednesday, 4 September 1991

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FP-4H2-6

C. Schiepers, J. Nuyts, L. Mortelmans, M. De Roo Nuclear Medicine, U.Z. Gasthuisberg, Leuven, Belgium

R. J. Seitz I, Neurology, Stockholms Karolinska

A NEW METHOD FOR DETERMINATION OF CARDIAC VOLUMES WITH SPECT IMAGES

MAPPING OF HUMAN BRAIN FUNCTION BY MRI GUIDED STANDARDIZATION OF PET IMAGE DATA

C. Bohm 2, T. Greitz3, L. Eriksson 3 lDept, of University of Dtisseldorf, 2Dept. of Physics, University, 3Dept. of Neuroradiology, Institute and Hospital, Stockholm, Sweden.

A rapid method was implemented for determining the total cardiac volume from a set of radially resampled transverse SPECT images. This method delineates the endocardial (EnW) and epicardial wall (EpW), and estimates LV volumes from these. The method requires the approximate location of the apex and long axis of the LV on transverse images. Determination of the EnW, EpW and basal plane of the heart was operator independent using a heuristic optimization algorithm. The pixels in transverse slices were converted to radial voxels, with a position dependent size. Summation of voxel volumes within the set boundaries yields the LV volumes. The method was calibrated and tested for reproducibility with a concentric cylindrical phantom of Tc-99m; results differed by less than 3%. A systemat i c volume overestimation of 27% was found. With this technique volume changes of rest and exercise cardiac perfusion imaging with Tc-99m MIBI was evaluated on 16 normal male volunteers. Average results in ml+l sd: LV volume rest exercise R/E r a t i o EnW lO0 + 17 91 + 21 l . l l + O.lO EpW 339 ¥ 38 317 ¥ 48 l.OB ¥ 0.07 The method was- applied to -resting studTes of lO patients who had an acute MI. EnW and EpW were detected even in cases where large and severe perfusion defects were encountered. The average EnW was If7 +55 and EpW 374 + 121 ml. WTth this robust technique LV volumes can accurately and easily by determined from SPECT Thallium and MIBI or PET ammonia and FDG images. The automaticity and r e l i a b i l i t y of the procedure will enhance its util i t y in the clinical setting.

Recently, it has b e c o m e widely r e c o g n i z e d that the analysis of PET image data has to relie on additional structural information from MR images. In particular, neurophysiological mapping of human brain function by PET demands point to point comparisons of identical anatomical locations in order to figure out task specific activity changes. In a joint study of the Karolinska Institute and Stockholms University a computerized brain atlas programme has been developed that aims at such integration of PET and MRI data (Bohm et al. Acta Radiol. (Suppl) 369, 449-452, 1986). By use of the computerized brain atlas programme individually shaped PET images can be spatially standardized applying a set of transformation parameters, These parameters are interactively determined on MR images for each subject and include linear and non-linear scaling parameters, angulations and position alignments. Thereafter, the spatially standardized PET images of different subjects can be averaged. Intersubject averaging reveals activity patterns with profoundly improved signal to noise ratio. It can be shown that the spatial standardization works with high accuracy both for the brain stem structures close to the midline and for the brain surface. It is the perspective of this project to create an atlas of the human brain which reflects the common sites of simple and higher order brain functions.

FP-412-1

FP-412-2

M.A. Nedelman, D. Shealy, R. Boutin, E. Brunt, I.E. Allen, H.F. Weisman, J.E. McCartney, F.D. Warren, H. Oppermann, R.H.L. Pang and H.J. Berger. Creative giomolecules, Hopkinton, MA and Centocor, Inc., Malvern, PA, USA. RAPID INFARCT IMAGING WITH A NEW Tc-99m ANTIMYOSIN RECOMBINANT SINGLE-CHAIN sFv FRAGMENT: EVALUATION IN A CANINE MODEL OF ACUTE MYOCARDIAL INFARCTION

JG F~eld I, TE Michaelsen 2, HB Benestad 3, and K Nustad 1

Studies of monoclonal antibody based imaging agents show that blood clearance is inversely proportional to molecular size, i.e. F a b > F(ab') 2 >IgG. Indiumiii antimyosin Fab-DTPA is a highly specific and sensitive marker for myocardial necrosis. We report here the first in vivo targeting of acute myocardial infarction with a novel recombinant single-chain sFv fragment. The sFv fragment is comprised of the heavy and light chain variable regions of antimyosin joined by a 15 amino acid linker. Technetium-99m (Tc-99m) labeling of the sFv was accomplished by attachment of a cleavable, ester-linked bifunctional chelator (RP-I). Comparative studies in mice showed Tc-99m sFv-RP-I cleared significantly faster (p<0.001) than Tc-99m Fab'-RP-I and In-lll Fab-DTPA antimyosin fragments. Furthermore, pharmacokinetics of Tc-99m sFv-RP-I in a canine model of acute myocardial infarction gave a t 1/2 of 0.54 + 0.13 hrs vs 2.80 + 0.57 and 2.58 + 0 . 6 4 hrs for Fab-UTPA and Fab'-RP-I (p<0.05), respectively. Despite its rapid clearance, Tc-99m sFv-RP-I had similar uptake in the infarct to that of the Fab'-RP-I and Fab-DTPA. In addition, infarct visualization was more rapid with the sFv. Thus, these data demonstrate antimyosin single-chain sFv possess characteristics necessary for rapid imaging of myocardial necrosis.

iThe Norwegian Radium Hospital, 2National Institutes of Public Health, and -Institute of Basic Sciences, Dept. of Physiology, University of Oslo, Oslo, Norway THE IMMUNOTARGETING DIFFERENCES BETWEEN RADIOLABELED IgG, F(ab' ). A N D Fab' IS M A I N L Y E X P L A I N E D BY T H E I R CONCENTRATION IN THE TARGET EXTRACELLULAR FLUID

In~nunoscintigraphy and immunotherapy of tumors with monoclonal antibodies are carried out either with intact IgG, or with enzymatically prepared fragments of the same immunoglobulin. Fragmentation of the antibody has influence on (i) the antibody binding characteristics, and (ii) the biodistribution of the antibody. When the purpose is to achieve the highest possible uptake in the tumor, it is advisable to use IgG. However, F(ab')2 or Fab should be applied when the purpose is to obtaln a high tumor/background ratio, either to avoid detrimental radioactivity dose to the normal tissues, or to increase the diagnostic specificity. In the study to be presented we have compared the specific target uptake with (i) the estimated association constant and number of effective binding sites on the target cells, and (ii) the concentration of available antibody within the extracellular fluid of the target. We applied an iterative nonlinear mathematical method for estimation of the binding parameters according to the mass action law, while a targeting model based on intraperitoneal diffusion chambers filled with the target cells made it possible to perform systematical in vivo studies monitoring both the specific target uptake, and the concentration of available antibody within the extracellular fluid of this target. The avidity of the F(ab') was close to the value achived with IgG. The avidity o~ the monovalent Fab was reduced to about 40-50% of IgG, but on the other hand the number of effective binding sites on the target was somewhat higher with this small fragment, presumably for sterical reasons. Thus, our conclusion is that the biodistribution difference between IgG and fragments is the main explanation of the targeting differences.

567

Wednesday, 4 September 1991

FP-412-3 ~.~'eh_er ~, J . Meindl ~, R, S e n e k o w i t s c h : , G. B r u c h e l t : , Th. Klinuehiel: H.-W. Pabst ~ : ~Sdear~dizinische ~inik der Technischen I~iversitAt Mfinchen, D-8000 Mihnchen 80, Ismanigerstr. ~,°n FRG ~Universit~tskinder'klinik Tfibin~en. [~7400Tdbingen. ~li~qtr 23. FRO 'I'UMOR SPH£~Oiu MODEL FOR THERAPY OF NEUROBL~STOMA HICROMETASTASES USING RADIO-IODINATED HIBG AND ANTI-GD2 (14.G2A) ANTIBODY Multicellular tumor spheroids are 3-dimensional spherical aggregates of malignant cells with a central proportion of mainly quiescent and hypoxic cells and an outer layer of proliferating ceils. Resembling small in vivo tumor a real~stic model for nodules spheroids provide micrometastases that we used for the simulation of in vivo responses to II25-MIBG-, II31-MIBG- and Ii31-HAbtherapy of neuroblastoma. In order to study the relationship between tumor size and therapeutic effect of II3I-MIBG or Ii31-iodinated AntiGD2 Antibodies spheroids of the cell lines SK-N-SH (active uptake of MIBG) and SK-N-LO (GD-2 positive) were cultured in bacteriological petri dishes on a shaking apparatus rocking the cells at a frequency of 10/min. Spheroids ranging from 90-250 pm in diameter were incubated for two hours with MIDG or antibody. The response of treated spheroids was assessed in terms of subsequent volume growth delay and outgrowth of individual cells on cell adhesive surfaces. Both If31 irradiation methods were more effective with the spheroid diameter increasing, whereas after II25treatment therapy effect was similar for both large and small spheroids. According to theoretical considerations the I131 irradiation dose increases with larger spheroid diameter, but MIBG uptake and radiosensitivity are diminished in the hypoxic core of larger spheroids. These results may contribute to explain why II31-MIBG therapy of diffuse bone marrow metastases is ineffective and support the use of MIBG as the initial therapeutic agent before chemotherapy.

FP-412-5 T. Leitha, A. Staudenherz, M. H0ttinger, P. Angelberger, R. Dudczak 1st Dept. Medicine, lust. Med. Chem. University Vienna, 0FZ Seibersdorf Te99m- & 1125-LDL KINETICS IN THE ISOLATED PERFUSED RAT LIVER

The purpose of this study was to compare 1125-LDL and Tc99m-LDL as possible tracers for quantitative assessment of LDL-receptor mediated processes in the liver. Tracer preparation: LDL was prepared from plasma of healthy human donors by sequential ultrazentrifugation. The iodine monochloride method was used for 1125 labeling. Tc99m labeling was performed by a modification of Lees et al. (J.NuclMed. 26; 1985). Tc99mLDL was isolated and purified by a combination of preparative HPLC on size exclusion colums (SEC) and subsequent dialysis for 2-6 hours in saline, 0.01 mM EDTA. Perfused isolated rat liver: Non-recirculating perfusions were performed for 120 min in the isolated liver of 9 Sprague-Dawley rats which received Tc99m- and 1125-LDL simultaneously 90 minutes before peffusion. The perfusate contained ca]ciumfree and blood-free Krebs-Ringer bicarbonate buffer, which was gassed continously with O2/CO2 (19:1) and maintained at 37 ± 0.5 °C. Biliary isotope excretion and release of breakdown products via the liver vein was analysed by protein precipitation with 20% trichloro:acetic acid and column chromatography. Results: Tc99m-LDL liver uptake (13.8-+1.6 %injected dose/90 min p.i.) highly exceeded 1125-LDL uptake,(2.6±0.6 %injected dose/90 min p.i.). This difference appeared to be mainly due to rapid release of low-molecular catabolites of 1125-LDL, since analysis of the venous effluens during 120 min of perfusion showed a release of 71.6-+9.4% of the initial 1125-LDL liveruptake. In compari'son total Tc99m release was significantly lower (7.9 +-1.6 % Tc99m-LDL liver-uptake). The biliary excretion of both isotopes was identical when correlated with the initial liver-uptake for both tracers and presumably reflects physiological LDL-receptor dependent biliary apoprotein B excretion. However, the protein-bound fraction of the biliary excreted activity was higher with Tc99m-LDL, probably due to in vitro dehalogination of 1125-labeled apoproteins in the bile. Conclusion: Quantitative assessment of LDL-receptor activity of the liver with radioiodinated LDL is hampered by its dehalogenation. In contrast Tc99m-LDL is trapped in the liver. The biliary excretion of a labeled high molecular catabolite of Tc99m-LDL indicate a LDL-receptor mediated apoprotein excretion.

568

FP-412-4 T. Leitha, M. HSttinger, A. Staudenherz, P. Angelberger, R. Dudczak 1st Dept. Medicine, Inst. Med. Chem. University Vienna, OFZ Seibersdorf Tc99m-LDL: IS IMAGING OF LDL-RECEPTOR ACTIVITY POSSIBLE? Te99m-LDL was compared with ]125-LDL to determine its possible role as tracer for quantitative imaging of LDL-receptor mediated processes. Tracer preparation: Human LDL was prepared by sequential ultrazentrifugation. The iodine mononhlcride method was used for 1125 labeling. Tc99m labeling was performed by a modification of Lees et al. (J.NucI.Med. 26; 1985). Tc99m-LDE was isolated and purified by a combination of preparative HPLC and subsequent dialysis. Radiochemical purity and in vitro stability was controlled by protein precipitation with 20% trichloro-acetic acid (PPJCA), column chromatography of both tracers and analytical HPLC and paperchromatography for Tc99m-LDL. Radiochemical purity: In contrast to 1125- LDL, Tc99m-LDL, purified by HPLC alone, showed a lower PP-TCA and a lower in vitro stability (1125: 96.8±2.5%; Tc99m: 68.5±10.66% 3h after labeling), whereas additional dialysis of Tc99m-LDL improved PP-TCA and its stability (86.2+_6.72% 3h after dialysis). Tissue culture assays: No significant differences between 1125- and Tc99m-LDL Were observed in simple displacement assays in fibroblasts and HepG2-cells. However, comparing the biological activity in 37°C uptake assays, differences between both tracers suggested an additional binding/internalization process for Tc99m-LDL, possibly due to uptake of a fraction of the tracer which was alterated by the labeling process. Animal studies: The biological relevance was tested in homozygote Watanabe heritable hyperlipidemic rabbits (WHHL) and New Zealand White rabbits (NZW), which differ in their LDLreceptor activity. 1125-LDL declined monoexponentially, whereas Tc99mLDL followed a biexponential function. The first component t~,5of Tc99m was 1-3h. The t½ of the second component was identical to the one of 1125-LDL. These values reflected the LDL-receptor activity of WHHL and NZ. The initial fast eflminafion of Tc99m-LDL may be explained by a labile fraction of Tc99m, or differences in receptor-affinity. Conclusion: Even optimized Tc99m LDL shows radiochemical heterogeneity and compared to 1125-LDL accelerated in vitro decomposition. Our data also suggest in vivo differences of both tracers, which may be due to tracer quality and receptor-affinity. Quantitative imaging of LDL-uptake with Tc99m-LDL may become possible, if the different components of Tc99m-LDL are kinetically resolved and considered.

FP-412-6A N. P. L.G. Verhoeff, B. van Vlies, ~i A W. Maas, de ~rumn, ~. ulivier, and E.~. van Royerg De~n~tments of Nuclear.and Experimental Internal Me[iicine, Academic Medical Centre, and Netherlands Institute for Brain Research, Amsterdam, and Cygne B. V., TU Einanoverb Tne NetherlanDs. IN VIVO BINDING OF MUSCAR~NIC CHOLINERGIC RECEPIDRS WITH 1-123 IODODEXETIMIDE IN RAT HEART 1-123 4-Iododexetimide (I-123 IDEX) ISl~_C. act. 5800 Ci/rmmol) has recently been syntheslzed by some. of us. The present study is an attempt to vaiidate this l i g ~ for muscarinic receptor binding by an in vivo study in rat heart. . in vivo upt.aKe of DU p.ul 1-123 IDEX in rat brain was st-udi'ea at various time points after injection in tile tail veirL Various neart regions ~ r e dissected and counted for radioactivity: sinoatrial node (SN), right atrium (RA), le~t atrium ,(LA), right ventrmcle (RV), ~ left ventricle (LV). Ratios o~ count rate aensi~y to une blood (BL) and to the left ventricle were taker& Results

SN RA LA RV LV

(Region/BL; X-+ SD; n = 3):

~ n after 15 35.9 38.1 -+0.9 +-7. 1 41.5 50.4 -+3.8 -+15 40.3 48.9 •+0.6 -+ii 25.0 20.5 -+1.9 -+2.5 23.4 19.2 •+0.8 +2.9

injection i~bi. 30 80 16.7 21.5 14.1 -+4.8 -+2.2 -+2.4 30.5 26.9 15.2 -+5.9 -+3.2 -+0.9 24.3 27.8 15.5 -+12 -+5.8 -+0.9 Ii.i 7.9 5.6 -+1.7 -+0.7 -+1.2 10.1 7.5 5.2 -+1.2 -+0.7 -+I.0

~40 9.9 -+0.5 13.1 -+1.8 12.8 +2.3 4.6 -+0.5 4.3 -+0.3

1440 13.6 -+5.1 13.5 -+4.7 16.6 -+6.4 4.8 -+1.5 4.1 +1.2

The ratio Region/LV increased from I. 53 -+ 0.02 (SN), 1.77 + O. I0 IRA), 1.72 -+ 0.09 (LA), and 1.06 + 0.04 (RV) at 5 mmn p.i. to 2. 88 -+ 0.03 (SN), 3. 47 +_ 0.12 (RA), 3. 71 ± 0.47 (LA), and 1.05 -+ 0.01 (RV). NO slgnificant further increment in the ratio Regiofl/LV was obeeryea after this time u~ to 24 h p.i. 1-123 IDEX may De usezul zor near~ Mreceplzor imaging in vivo at 1 hour after injectior~

Wednesday, 4 September 1991

FP-412-6B

FP-4D3-1

N. P. I~ G. Verhoeff, A. v a n Breukel, NL A_ W. Maas, a n d ~:.b. v a n FuDyera .De~grtments. o f Nuclear. a n d E x p e r i m e n t a l I n t e r n a l Meo~czne, A c a a e m i c M e d i c a l C,e~tre, a n d N e t h e r l a n d s I n s t i t u t e f o r B r a i n Research, Amsterdam, a n d C y g n e B.V., T U Einunoven, 'ine N e t h e r l a n d s .

D.Cantalupi*, T.Varettoh C.Poti*, C.PoTta**, F.Peinetti** and D.Palombo** Nuclear Medicine Department* and Vascular Surgery Unit** Regional Rospital. Viale Ginevra,3. ii100 Aosta ITALY

IN VIVO BINDING OF MUSCARINIC CHOLINERGIC WITH 1-123 IODODEXETIMIDE IN RAT BRAIN

ASSESSMENT OF CEREBROVASCULAR RESERVE CAPACITY USING 99mTc HM-PAO SPET AND TRANSCRARIAL DOPPLER WITH DIAMR× TEST IN CAROTID SURGERY In order to evaluate the baewodynamic risk of impending strophe and of cerebral isehaemia after carotid clamping during thrombeendartereetomy (TEA), we assessed eerebrmvascular reserve capacity with 99mTe HM-PAO SPET and with Transcranial Doppler (TCD) after giammx provocative test in patients candidate to carotid surgery. From January to November 1998 we studied 34 patients 08 surgical procedures) with SPET and TDD before and after surgery. All patients underwent intraoperative monitoring with TDD and Domatnsensmry Evoked Potentials (SSEPs). We evaluated cerebral perfusion and mean velocity in the middle cerebral artery (MCA) baseline and 28 minutes after i.v. injection of i g of Acetazolamide (Diamox). We propose a simple~emiqoantitative method to compare the two perfusion exams before and after the test, avoiding problems araising from different doses and possible different behaviour of the tracer. Percentage increments were calculated for both data. Results: perfusion increase > IB% 89% of our patients perfusimn increase ( 5% 11% of our patients ~ean velocity increase > 28% 82% of our patients mean velocity increase < 20% 5% of our patients mean velocity increase ( 10% 13% of our patients All patients with perfusion increase lower than 5% and/or with velocity increase lower than 10% were shunted intraopermtively because of severe abnor=alities in SSEPs developed during carotid clamping. Neither ~ortality, nor neurological deficits resulted after surgery. We can therefore assume that a poor vasodilatation after provocative test (perfusion increase lower than 5% and/or velocity iBcrease lower than 10%) enables us to select those patients at risk of stroke and thenefore candidate to intraoperative shunting during carotid surgery. Furthermore this allows us to avoid the risks (cerebral thrmmboemholism and technical errors) associated with an indiscriminate mee of carotid shunting.

RECEPTORS

1-123 4-Iododexetimide (I-123 IDEX) (sp@e. act. 5800 Ci/rmmol ) has r e c e n t l y b e e n s y n t h e s i z e d b y s o m e oz u@. T h e p r e s e n t s t u d y is a n atter~ot t o vaA~oaue ~nls l~gar~ for muscarinic receptor b i n d i n g b y a n i n v i v o s t u d y i n r a t brairL I n v i v o u p t a k e o f 50 0 C i 1 - 1 2 3 I D E X i n r a t brain was studied at various time points after i n ] e c t l o n z n t h e t a i l veir~ V a r i o u s b r a i n r e g i o n s we.re d i s s e c t e d a n d c o u n t e d f o r rad/oactivit!n o l f a c t o r y b u l b (OB), m e d u l l a - D o n s (MP), frehtal c o r t e x ( F C ) , l i m b i c s y s t e m (LT), s t r i a t u m (ST), 13arie .r~. c o r t e x (PC), h y p o t h a l a m u s (HT), a m y q d a l a ~AM), hi~ppoc .a.mpus (HI), - o c c i p i t a l c o r t e x (OtJ, OOIilCLLLI (t~)), arKl tlD~9_Lalrg/S (TH). Ratios o f c o u n t rate density to the cerebellum (CB) w e r e takern R e s u l t s ( R e g i o n / C B ; m e a n value; n = 3): M / n a f t e r i n j e c t i o n (p. i. ) 5 15 30 60 120 240 1440 O B 0.92 1.23 1.97 2. 15 2. 84 1.07 5. 95 M P 0.98 I. ii 1.32 1.65 1.77 2 . 9 5 3.53 F C 1.27 1.87 3.17 4 . 2 4 6 . 0 0 2 . 5 2 17.0 LI 1.09 1.47 2.09 3.11 4 . 0 4 2 . 6 5 11.6 S T 1.19 1.49 2.37 3 . 4 7 5 . 0 6 1.23 13.8 P C 1.32 1.80 2.62 4 . 0 8 5 . 3 8 3 . 0 8 16.6 H T 1.04 1.20 1.45 1.81 2 . 2 4 2.84 5.70 A M i. i0 1.41 2. 07 3 . 0 5 4. 21 2. 24 15.9 HI i. 12 1.53 2. 31 3. 18 4. 39 3. 18 24.8 O C 1.22 1.77 3 . 1 0 4 . 1 8 5 . 3 9 0 . 7 4 16.1 C O i. 16 1.35 1.54 2 . 0 4 2. 18 0. 37 5. 91 T H 1.07 1.24 1.50 2 . 0 5 2 . 4 6 1.36 5.99 T h e r a t i o / C B i n c r e a s e d i n r e g i o n s w i t h a h / q h Mr e c e p u o r (tensity (HI, FC, PCs CC, AM, arg~ ST). T h e i n c r e m e n t w a s less p r o n o u n c e d ic~q M - d e n s i t y regions. 1 - 1 2 3 I D E X ~ m a y D e u s e f u l z o r b r a i n Mr e c e p t o r i m a g i n g i n v i v o a t a l o n g e r t i m e (24 h) p.i.

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FP-4D3-3

M.Clausen, R.Weller, B.Kleiser, H.Kurz, E.Henze, B.Yidder, J . L a n g h a n s , E . S i g m u n d , H . K o r n h u b e r , Y . E . A d a m Nuclear Medicine, Neurology, U n i v e r s i t y Ulm, Germany N u c l e a r M e d i c i n e B W K Ulm, G e r m a n y

Neurological Clinic of Vienna, Lazarettg.14, 1090 Vienna, Austria

D I S T U R B A N C E S O F A U T O R E G U L A T I O N OF C E R E B R A L P E R F U S I O N SONOGRAPHY (TCD-CO2DETECTED BY TRANSCRANIALDOPPLER TEST) AND BY BMPAO-SPECT. In patients with significant stenosis of the internal c a r o t i d a r t e r y (ACI) a r e d u c e d a u t o r e g u l a t i o n of c e r e b r a l p e r f u s i o n may be d e t e c t e d by HMPAO-SPECT during n o r m o - a n d h y p e r k a p n i a . The clinical relevance of this p r o c e d u r e is c o m p a r e d to the TCD-CO2-test in this study. 17 patients with one- or t w o - s i d e d (sub-) total s t e n o s i s of the ACI are i n v e s t i g a t e d . Of the 34 cerebri media p e r f u s i o n a r e a s 17 h a v e an intact and 17 h a v e a reduced or n o n - e x i s t e n t a u t o r e g u l a t i o n in the T C D - C 0 2 test. The H M P A O - S P E C T d u r i n g n o r m o - and h y p e r k a p n i a are acquired w i t h i n 3 days, u s i n g a r o t a t i n g s i n g l e - h e a d e d camera. The organ position is corrected in all 3 d i m e n s i o n s . O r g a n s i z e and s h a p e is s t a n d a r d i z e d by the circle r e f e r e n c e m e t h o d e ( Y e l l e r 1989). In p r e d e f i n e d ROIs count r a t e s are n o r m a l i z e d to c e r e b r a l activity and e x p r e s s e d in p e r c e n t (~) to a set of n o r m a l values. The autoregulation index (ARI) is d e f i n e d for each cerebri m e d i a r e g i o n by h y p e r k a p n i a ( ~ ) - n o r m o k a p n i a ( ~ ) . For 34 c e r e h r i m e d i a p e r f u s i o n a r e a s the ARI has a s e n s i t i v i t y of 8 2 ~ and a s p e c i f i c i t y of 94~ c o m p a r e d to the T C D - C O 2 - t e s t . Only 71~ and 6 7 ~ is found w i t h a simple r i g h t - l e f t r a t i o w i t h m a n u a l l y d r a w n ROIs. Quantification of c e r e b r a l perfusion by u s i n g the reference circle method enhances the d i a g n o s t i c performance of H M A P O - S P E C T . Y i t h a s i m p l e ARI a reduced autoregulation can be expressed numerically. In addition and surpassing ultrasound information the imaging procedure may differentiate r e g i o n a l effects. Yeller R, Henze E, Clausen M, Adam gE (1989): Quantification of amplitude images of RNV: A new u n i v e r s a l method. J N u c l Med 3 0 : 1 3 9 3 - 1 3 9 8

Asenbaum S., Podreka I., W~ber-Bing~l. C.

CEREBR~L HMPAO DISTRIBUTION IN CHILDREN WITH EPILEPSY - A TC99M HMPAO SPECT STUDY The aim of the present study was to describe interictal changes of HMPAO uptake in children, to relate them to the various diagnosis and EEG-reports, to compare the relative uptake in special ROI's with a norm population and to look at connections of HMPAO uptake between different cortical regions. HMPAO SPECT was performed in 17 children (7-20 years of age) suffering from seizures. All had normal CAT scans. Generalized tonic-clonic seizures (GM) occured in 9 patients, absences (A~) were observed in- 4, simple partial seizures (SP) in 1 and partial complex seizures (PC) in 5 patients, whereby 2 patients suffered from GM and A~ and 1 patient from GM and PK as well. BEG showed diffuse abnormalities in i0 children, focal abnormalities in 8 and was normal in 2 children. -SPECT studies were evaluated visually and by calculating ratios of tracer distribution (regional index(RI)=(mean counts/voxel of ROI)/(mean cts/voxel of all ROI)) in 32 ROIs covering predominantly gray matter, which were drawn on 4 adjacent, 21.9 mm thick transversal slices. RI were compared to those obtained in a control group (mean age 25 years). Abnormal SPECT findings were present in 16 instances. A reduced HMPAO deposition in the left temporal lobe was obvious in ii patients, in the right temporal lobe in 5 patients and in the left frontal cortex in 9 cases. An interesting finding was, that all patients with PC showed a combination of temporal and ipsilateral frontal alteration of tracer distribution, and that more than half of the GM-patients had temporal alterations as well. -EEG and SPECT findings were congruent only in 4 out of 8 patients. -The comparison of the RI demonstrated a relativly increased uptake in the upper cortical layers in ii patients (especially central and parietal) and a relativly reduced uptake in the inferior frontal cortex in 15 and in the temporal lobe in 9 patients. We conclude, that alterations in HMPAO uptake were present in a high percentage of epileptic children, especially in the left frontal and temporal cortex, regardless of the seizure type. There was a strong connection between the diagnosis PC and temporal/ipsilateral frontal abnormalities. -The comparison of the EEG and SPECT findings revealed only a weak correlation. Since most of the patients with a reduced RI in the inferior frontal cortex had ipsilateral alterations in the temporal HMPAO uptake, this com]Dination might indicate, that several other brain regions besides the temporal lobes show an impaired function.

569

Wednesday, 4 September 1991

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AH Huneidi. MJ Carroll, J Bomanji, P N Plowman, F Afshar, KE B r i t t o n . Depts. of N e u r o s u r g e r y & N u c l e a r M e d i c i n e . St. B a r t h o l o m e w ' s H o s p i t a l , London.

L.Pgvics, A. Kuncz, E. Ambrus, T. D6czi, M. Bodosi, and L. Csernay, Albert Szent- GySrgyi Medical University, Szeged, H u n g a r y

SPET HAEMODYNAMIC FUNCTIONAL CLASSIFICATION OF C E R E B R A L A R T E R I O V E N O U S M A L F O R M A T I O N S 1,6 y (9 T w e n t y p a t i e n t s , m e a n age of 3 5 . 3 ± males), p r e s e n t e d w i t h c e r e b r a l h a e m o r r h a g e and or epilepsy due to arteriovenous malformations (AVM) as p r o v e n b y h e a d CT scanning and cerebral angiography. They were studied prospectively with dynamic c e r e b r a l b l o o d f l o w a n d b r a i n SPET at the same session using non-diffusible human s e r u m a l b u m i n l a b e l l e d w i t h T c - 9 9 m (600MBq). Two types of A V M c o u l d be i d e n t i f i e d : i. F a s t f l o w A V M (55%) w i t h a f f e c t e d to nonaffected hemisphere f l o w ratio 1.31 ± 0.04 a n d m e a n t r a n s i t time ratio of 0.85 ±

0.03. 2. S l o w f l o w A V M (45%) w i t h a f l o w r a t i o of 0.92 ± 0.06 and a m e a n t r a n s i t time r a t i o of 1.13 ± 0.03, which tended to be m a i n l y v e n o u s AVM. T h e s e d i f f e r e n c e s w e r e s i g n i f i c a n t for b o t h transit time and flow (p<0.001). With s t e r e o t a c t i c r a d i o s u r g e r y t r e a t m e n t the fast f l o w A V M g r o u p t e n d e d to s h o w r e d u c t i o n of v o l u m e a m d s l o w i n g of flow. This assessment m a y be of p r o g n o s t i c value.

T H E R O L E O F COMBINED r C B F - r C B V S P E C T STUDIES IN THE EVALUATION O F INTRACRANIAL ARTERIOVENOUS M A L F O R M A T I O N S (AVM) Thlrty-four brain perfusion (rCBF)(99mTc-HMPAO) and 32 blood volume (rCBV)(99mTc-RBC) investigations w e r e performed b y S P E C T on 17 patients with intracranial AVM. In 14 cases, surgical resection of the A V M w a s also carried out. In 15/17, the r C B F revealed a decreased tracer uptake at the site of the AVM. In the rCBV SPECT, abnormal AVM structures with increased radioactivity w e r e d e t e c t e d in 13/16. For recognition of the marked cerebral ischemla around the AVM, the sizes of the perfusion abnormalities w e r e c o m p a r e d with the blood volume disturbances. Preoperatively, the cerebral perfusion defect w a s equal to or greater than the volume changes in 7/14. In the c a s e w h e n the r C B F abnormality w a s equal to (as concerns the radiation scattering) or larger than the r C B V disturbance, a marked Ischemia w a s considered to be present around the AVM. Via this Criterion, the appearance of a normal perfusion p r e s s u r e breakthrough (NPPB), a serious interor postoperative complication of AVM resection, could be predicted in 5/6 cases. Postoperative follow-up brain SPECT studies showed the hemodynamic changes due to the surgical intervention in a g r e e m e n t with the neurological condition. It w a s concluded that combined rCBFr C B V S P E C T is a useful m e t h o d to clarify the hemodynamic effects of intracranial AVM. It is helpful in planning the surgical intervention, and in the follow-up.

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O.MIGNECO 1, J.DARCOURT 1, V.AUBIN2, J.BENOLIEL 1, O.RICQ 2, P.ROBERT 2, ZX.HE 1, J.MAGNE 1, G.DARCOURT 2, F.LAPALUS 1. Dpts of 1 Nuclear Medicine Ctre A. Lacassagne and 2 Psychiatry Pasteur Hosp. University of Nice. France.

M.T.DORDAL', M.BALTASAR*, M.T.SERVER', J.BOTEY', DE, J.M.GONZALEZ, F.PORTA, D.ORTEGA. SERVEI DE MEDIClNA NUCLEAR. SERVEI D'AL.LERGIA PEDIATRICA. HOSPITAL GENERAL "VALL D'HEBRON". BARCELONA - 08035. SPAIN. ESOPHAGEAL SClNTIGFIAPHY IN CHILDREN WITH RECURRENT BRONCHITIS UNDER ANTI-REFLUX TREATMENT : FIRST RESULTS OF A PROSPECTIVE STUDY. INTRODUCTION: The relationship between recurrent bronchitis (RB) and gastro-esophagea! reflux (GER) is well known end accepted in the literature. Esophageal scintigrsphy (ES) is a highly sensitive technique to detect esophageal abnormalities secondary to GER in children. Prospectively, we evaluate the effects of anti-reflux treatment in children with RB. Esophageal scintigraphy is used to detect pre and post-treatment esophageal motility abnormalities. MATERIAL AND METHODS: 16 children (8 females, 8 males, 3.5 to 12 years, average 6.7 years) with spasmodic cough with or without RB and with pathologial ES, have been submitted to a medicament (Domperidone) and dietetico-postural antirefiux treatment. Previously, they were evaluated by means of clinical score, inmunoallergy, cutaneous test, Xray GE transit and ES. After 3 months of treatment, a new clinical score with respiratory and gastrointestinal evolution was obtained end a new ES was performed. RESULTS : In 12/16 ES became completely normal 3 months after treatment and clinical evolution was very good (cough and digestive symptoms disappeared, lower frequency in RB episodes) except in one case, in which cough persisted. In 3/16 esophageal retention on ES diminished but without becoming normal, one had no symptoms, in another gastric symptoms disappeared and two continued to present irritative cough, less than prior to treatment. In one case, ES remained unchanged (short esophageal retention), but clinical evolution was very good, without cough or gastric symptoms.

MAJOR ROLE OF RIGHT TEMPORAL LOBE (RT) INVOLVEMENT IN ALZHEIMER TYPE DEMENTIA (AT/)) We investigated the changes of regional cerebral blood flow related to cognitive impairment in ATD and found that RT involvement plays a major role. 28 patients and 8 age matched controls were included. The global deterioration was measured by Mini Mental Status (I~IMS). Controls and a subgroup of 12 patients were also evaluated by a Hierarchic Dementia Scale (HDS) which independently tests 20 cognitive and motor functions. While solving a visual task, the patients were injected 750 MBq of 99mTc-HMPAO in an IV line. One hour later, the tomographic acquisition was performed. To quantify the data, we used two computed lateral views of the cortex, where the regions of interest (ROI) were automatically delineated, using a proportional stereotaxic atlas. The ratios of cerebral ROIs over.the cerebellum were calculated.The most significant difference of HMPAO uptake between ATD and conlxols was in the right parieto-temporal area (RPT) and RT (p<0.01). Tkere was also a significant non linear correlation of the MMS results with RPT (p<0.001) and RT (p<0.01). The global deterioration, tested by MMS, can modify the HDS scores. By using partial correlation between MMS, lIDS items and HMPAO uptake, we corrected the data for the influence of global deterioration on HDS performances. Under this conditions, we found that RPT and RT correlate (p<0.01 and p<0.05) with constructional apraxia. We conclude that RT lobe is mainly involved in ATD, and is directly responsible for constructional apraxia symptomatology.

570

CLINICAL SYMPTOMS

ESOPHAGEAL

SCINTIG,,AP,Y

Better Cough TOTAL _~i ii ii Normal-~] i~ 142 Pa,ho, It

DISCUSSION : High percentage of esophageal pathology has been described in children with RB ( 55-60 % in our Service in a previous series, N=212). ES has been useful in this selected group of children to document the normalization of esophageal function after 3 months of anti-reflux treatment with very good clinical evolution.

Wednesday, 4 September 1991

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A. PieDsz. M. P. Derde, H. Pintelon, Y. Vandenplas AZ VUB, Depts Radioisotopes and Paediatrics, Brussels.

J D Danbenton, M D Mann, Department of Paediatrics and Child Health, • University of Cape Town and Red Cross War Memorial Children's Hospital, WOO Rundebosch, South Africa

•SIMULTANEOUSLY PERFORMED pH MONITORING AND GASTROESOPHAGEAL REFLUX (GER) SCINTIGRAPHY IN CHILDREN Owing to the variable and often contradictory results published in the literature, we compared, on a minute per minute basis, both pH metry and scintigraphy, in order to analyze the differences and complementarity of both examinations for the detection of GER. Sixty five children underwent routinely and simultaneously these two tests ; GER scan was performed during a one-hour recording period and the beginning and the end of the radionucitde test was marked on the pH recording device. The pH recording was further prolonged during a total period of 24 Hr, During the simultaneous 1 Hr recording period, the reflux phenomenon was detected more frequently by scintigraphy than by pH metry, using the classical criterion of a pH drop below 4.0 : in 37 children, no reflux was detected ; in 21 patients, the reflux was detected only on scintigraphy ; in 2 patients, only pH merry was positive and in 5 patients, both examinations were positive, in terms of reflux episodes, 123 episodes were recorded among the 28 refluxing patients; 88 episodes were recorded by scintJgraphy and 13 by pH metry ; only 1 episode was recorded simultaneously with both techniques. These data might partially be explained by the fact that gastric activity was buffered by the milk feeding used for scintigraphy. The comparison of 1 Hr scintigraphy and 24 hr pH recording yielded even more surprising results : the 2 examinations were both negative in 25 patients and both positive in only 6 patients. In 13 patients, pH metry was positive for reflux, while scintigraphy was negative ; in 21 cases, only scintigraphy could clearly detect the reflux phenomenon. It is concluded that pH merry alone leaves undetected an important number of refluxing patients. The consequences of it, in clinical situations like recurrent lung disease, are to be kept in mind.

THE INTERPRETATION OF SCINTIGRAPHIC STUDIES IN INFANTS WITH COMPLETE CHOLESTASIS Differentiation between extrahepatic biliary atresia (EHBA) and the neonatal hepatitis syndrome (NHS) is important in an infant with cholestasis as laparotomy is always indicated in EHBA but is undesirable in NHS. This differentiation is particularly difficult in those infants with complete cholestasis. Hepatobiliary seintigraphy is a commonly used investigation in infants with obstructive jaundice. The clinical or scintigraphic demonstration of excretion into the gut excludes extrahepatic obstruction but absence of excretion may be due to EHBA, severe cholestasis with patent extra.hepatic bile ducts or poor uptake of the agent, and is therefore not diagnostic. This study examined the value of the quantitative measurement of hepatic uptake of 99mTc-p-butyl IDA and Sn-colloid in a group of 28 patients with complete cholestasis in whom conventional scan interpretation, based on excretion into the gut, would not be useful. In 16 of the patients the final diagnosis was EHBA and in 12 NHS. The scans were recorded as dynamic studies. The time-activity curves of blood pool and hepatic regions of interest were subjected to iterative, non-tinear curve fitting to calculate rate constants for the uptake of the radiopharmaceuticals. There were significant differences between the EHBA and the NHS patients in the rate of uptake of p-butyl IDA and in the ratio of the rate of uptake of p-butyl IDA to the rate of uptake of colloid. Using this method of scan interpretation a diagnostic accuracy of 85% was achieved in this study of patients who clinically and scintigraphically had no evidence of bile flow. We also noticed that the shape of the liver differed in the two conditions and confirmed this by simple measurements. Hepatic scintigraphy is therefore a useful investigation in the diagnostic work-up of infants presenting with obstructive jaundice even when bile flow is completely absent.

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J, K0tzerke. H. v.d. Hardt, R. Beyer, G.-J. Meyer, H. Wiese, J. Seidenberg, H. Hundeshagen. Abt. Nuklearmedizin und spez. Biophysik, Abt. Kinderheilkunde der Medizinischen Hochscbule Hannover und Zentralinstitut for Kernforschung, Rossendorf, Germany

GUILLET J.,ROLE C.,BILLEAUD FRANC M., RICHARD A.

INTRODUCTION OF A NEW PARTICLE FOR ASSESSMENT OF THE MUCOCILIAR TRANSPORT FUNCTION IN CHILDREN In pdmary or acquired disorders of ciliary clearance, the ex vivo evaluation of motility and morphology is not sufficient for the assessment of bronchial transport function. A regional and functional in vivo analysis of mucociliar clearance can be obtained with a nuclear medicine procedure. The deposition pattern of inhaled particles depends on methodological variables as the kind and size of particle used, the nebulizing system, and the breathing pattern. Therefore normal values for global and regional clearance rates vary according to the methodological variation of central deposition, particle size, and the method of clearance calculation. Interindividual comparison of mucociliar clearance and the influence of medication accordingly require a standardization and a minimalization of the remaining variability. Influence of different breathing patterns can minimized by using a monodisperse spherical particle of about 6+2 p.m. For this reason we have labelled a newly developed micorsphere (MS) of 7.4 (Og =1.3) ~ with 99mTC and volatized it with a pressurized air nebulizer. Inhalation was performed at slightly increased breathing depth. After 20 breathing cycles (deposition of about tO MBq 99rnTc-MS) a dynamic study was started (1 frame/min for 45 min). To calculate ciliary transport, counts were decaycorrected and the central clearance function was corrected for peripheral inflow per time-unit. In severly ill cases the remaining activity at 24 hrs could be measured.To assess ciliary kinetics the initial deposition pattern, regional clearance curves, and retention after 24 hrs were used. 14 children and 4 adult lung transplanted patients were investigated. In normal function (n = 14 studies), the global clearance was 53% (38-65%) in the first 45 minutes. In decreased ciliary function (n=l 1 studies), the initial clearance was 17% (7-25%) and the 24 hrs-retention was 54%(25-84%). The examination of mucocitiar transport function in nuclear medicine serves as valuable addition to pulmonary diagnostics, and can, most importantly in in young patients without discomfort. The new MS-padicle has been proven to be deposited uniformly in the large bronchi without employment of special breathing techniques.

C., LAVAL M., JOUSSEIN

Paediatrio Nuclear Medicine Department. talier 4?023 AGEN CEDEX-FRANCE

M.,

Centre Hospi-

PROGNOSIS VALUE OF SPECT N ISOPROPYL IODO 123 1 AMPHETAMINE : 255 NEONATES. Clinical neurological examination and currently available methods of assessment, (EEG., Evoked Potentials, Ultrasonography, Computed X ray Tomography) are frequently unable to predict the extent of the brain damages in neonates. Brain Functional Assessment with N isopropyl iodo amphetamine is an interesting way for prognosis evaluation. Materiel and methods I) Experimental study : A toxicological study was performed in 155 wistars newborn rats. 2) Clinical study : - radiopharmaceutical dose 123 I : 925 MBq/kg ; IAMP 0,70mg/kg, injected intravenously or through umbilical arterious or venous catheter. - tomographic acquisition (360 ° rotation, 30-35 mn, SPECT camera) completed with a whole body scan. - clinical follow up done up to 6 years after the first IAMP examination. Results : Dosimetric considerations are acceptable : 0,2cGy for the critical organ (lungs). Data interpretation must be made through normal maturation patterns. Abnormal global or focal defects are well correlated with a poor prognosis. But a few neonates with a very high uptake on the first investigation may have sequellae. The sensitivity is higher than with clinical or morphological examinations and EEG. The specificity is higher than with EEG or evoked potentials. Conclusions :lAMP is a good way to determine a "at risk" group of children, who must be carefully followed up by the paediatrician, since an early rehabilitation is more efficient.

571

Wednesday, 4 September 1991

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Gordon, MOrton, T Hughes, R Dinwiddie. Hosp. for Sick Child., London UK

N.W. Morrell, W.A. Seed, C.M. Roberts, B.E.Jones, K. Nijran, T. Biggs. Departments of Medicine and Nuclear Medicine, Chafing Cross Hospital, London U.K.

EVALUATION (rCBF) IN CHILDHOOD

OF REGIONAL CEREBRAL PERFUSION ACUTE NEUROLOGICAL DISORDERS IN

Twenty three children, mean age 4.1 yrs. ( r a n g e 15 d a y s - 13 y e a r s ) u n d e r w e n t both CT brain and Tc-99m HMPAO scans for acute neurological disorders to assess the role of T c - 9 9 m H M P A O i n c h i l d r e n with meningitis, encephalitis, suspected but unproved infection or an altered state of blood pressure. Nine children had focal abnormalities on b o t h CT a n d T c - 9 9 m H M P A O s c a n s , 5 c h i l d r e n with a focal abnormality on HMPAO had a normal CT scan, 2 children had normal studies. Four children had a focal abnormality on Tc-99m HMPAO but a generalised abnormality on CT. Two children with a generalised abnormality o n CT h a d a n o r m a l HMPAO and one child with a focal abnormality on CT had a normal Tc-99m HMPAO scan. Correlation with clinical findings at the outset of the illness w a s g o o d i n 16 children on both Tc-99m HMPAO scan and CT scan. CT scans are undertaken in a l l c h i l dren with acute neurological disorders who require hospitalisation. Tc-99m HMPAO s h o w e d a b n o r m a l r C B F in 7 8 % of t h e s e c h i l d r e n , h a l f of w h o m h a d a n o r m a l C T s c a n .

LOBAR & SEGMENTAL ANATOMY OF RADIONUCLIDE LUNG SCANNING In the interpretation of ventilation-perfusion scans for the diagnosis of pulmonary embolism, much emphasis is placed on the size and location of perfusion defects: those with segmental distribution are given higher probability for pulmonary emboIism. Despite this, little has been done to demonstrate the precise appearance of known segmental and lobar defects in human subjects, which is the aim of this investigation. We have used fibre-optic bronchoscopy under local anaesthesia (with ethical committee approval) in volunteers with normal lung function and no history of chest disease to piace sequential temporary occiuaions at lobar and segmental levels using a small balloon catheter introduced via the instrument channel of the bronchoseope. With each occlusion in place, ventilation studies were performed in the posterior, posterior-oblique and lateral projections using 81m-Kr with the subject positioned over a gamma camera. Anterior views were included only if it were thought they might add extra information. Counts of 250 to 300K were obtained in each v i e w . Using this technique we have mapped out the precise lung scan appearances of anatomically known lobar and segmental defects using an isotope (81m-Kr) that gives similar resolution to 99m-Tc used in perfusion imaging. This study demonstrates that the appearance of k n o w n segmental defects may he different from those predicted from anatomical drawings and models in terms of size, shape and location, especially in the basal segments. An appreciation of these differences may have important implications in improving the diagnostic accuracy of ventilation-perfusion scanning for pulmonary embolism and for the optimal visualisation of defects.

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FP-4H3-3

L.Galuska, J Miller Dept. of Nuc. Ned. of County Hosp. Kecskem6t

I. Brandhorst*, M. Rust+, H. Miiller#, B. Schulze*, G. H6r~ *Institute for Diagnostic Imaging; +Div. of Pulmonology; #Div. of Pathology; -DiV:" of Nuclear Medicine; University Hospital Frankfurt/Main, F.R.G.

Inst. of Isotopes of the Hung. Academy of Sciences Budapest, HUNGARY PULNOTEC A NEW ULTRAFINE 99mTc AEROSOL INHALATOR; THE FIRST CLINICAL RESULTS The PULNOTEC is a newly developed device to produce superfine dry aerosol /pseudogas/ from common 99mTc-saline. The 99mTe-DTPA wet aerosol /produced in MEDI 61/ inhalative scans were compared on So adult persons /io normals 20 obstructiv patients/ with PULNOTEC results. Methodically the analogous pictures and 3o sec 32 frames, stored in computer were analysed. Depostition patterns as "Penetratfon Index" /PI/ percent of central and periferial lung ROI CPM were expressed. The "clearance half time" /CTI/2/ of whole lung projections were calculated from time-activity curyes. Results: 99mTcDTPA/MEDI61/ 99mTcPULNOTEC PI CTI/2 PI CTI/2 Normals 75 /8/ 62/14/ 11o/16 115/14/ Obstruct dS/12/ -78/16/ lo5/14/ iao/22/ /CTI/2 in minutes, PI in percent, mean of two lung projections and SD are reported./ Conclusions:' i. Instead of 2 or more minute inhalation, it is enough 2-3 breaths from PULMOTEC "pseudogas" to make good quality scans. 2. There isn't central deposition of activity on PULMOTEC scans at obstructive patients. S. The PULMOTEC gives possibility for more than two ours to make good inhalative scan of lungs. Affer half an hour of inhalation the thyroid gland and stomac is visible on PULMOTEC scans, as it is usual at aerosol inhalation pictures.

572

TC99m-HSAMM VERSUS GA67-CITRATE IN THE DIAGNOSIS OF OPPORTUNISTIC LUNG INFECTIONS IN AIDS PATIENTS. The very early detection of opportunistic infections in AIDS pts. even today with all the new prophylactic possibilities is still most important for starting successful therapy. This investigation was undertaken to compare the diagnostic usefulness of Tc99m-Human-Serum-Albumine-Milli-Microspheres (Tc99m - HSAMM) vs. 67Ga-citrate in the diagnosis of opportunistic lung infections. In 19 consecutive HIV positive pts. (1 female, 18 males; mean age 40 yrs. (21 - 64 yrs.) suffering from dyspnea and cough we performed Ga67-citrate (2.5 MBq/kg body weight) and Tc99mHSAMM (5.5 MBq/kg body weight) scintigraphies. Images were fabricated 40rain. (Tc99m-) and 3 days (Ga67-) after intravenous injection of the radiopharmaceutica. In 8 pts. with PeP both scans were pos. (I); in 3 pts. without lung infections both scans were neg. 0I); in 5 pts. without PcP but with other lung problems, neither the Ga67- nor the Tc99m-scans were pos. (III). In 1 pt. with diffuse malignant lymphoma of the lungs the Tc99m-scan was pos. (Ga-67 scan neg.!!!)(IV); another 2 pts. (1 varicella pneumonia, 1 mycobactedosis) showed pos. Tc99m-images (Ga-67 scans not done)(V). 99mTc-HSAMM lung scanning in AIDS patients is a promising new approach for noninvasive detection of opportunistic lung diseases even in normal x-rays and negative 67Ga scans. Further more it seems to be a very usefull method for shortening the time between injection and acquisition from 3 days down to 40 minutes for an early therapy beginning.

Wednesday, 4 September 1991

FP-4H3-5

FP-4H3-4 F Montravers, Paris, FRANCE.

JN Talbot

and JD Sraer.

H6pital

TENON,

PATIENTS WITH CHRONIC RENAL ~ FAILURE BUT WITHOUT EVIDENCE OF LUNG PATHOLOGY FREQUENTLY PRESENT PERFUSION DEFECTS ON LUNG SCINTIGRAPHY. We observed extensive pulmonary perfusion defects in some patients (pts) without history of lung pathology but with chronic renal failure (CRF), referred for a pretransplant examination. AS no systematic study appeared in the literature, we looked for lung perfusion anomalies in such pts. Methods : Pulmonary perfusion scintigraphy was performed using 99mTc labelled human albumin microspheres in pts with CRF. The extent and the severity of the defects were scored according to the perfusion component of the Miller's index (theoretical range : 0-18). Patients : 94 pts (66 male, 28 female, age 42,7±24.9 years) have been included. They had no history and no clinical sign of lung disease. 81 pts were undergoing hemodialysis (HD). Results : The score, observed in the 94 CRF pts, was 4.7±3.7 (range = 1-9). Values equal to or greater than 6 (definite defects extending on the equivalent of one lung or more) were observed in 30 pts (31%). The mean score value was greater in men than in women (4.9 ve 3.5 ; p = 0.04). The score was related with age but not with tabaqism, causal renal pathology or HD. In HD pts, the score was not related with duration of HD or with time elapsed between the lung scintigraphy and the last HD session. Conclusion : The frequent observation of extensive defects in chronic renal failure leads to recommend a pretransplant lung scintigraphy, in particular to facilitate the diagnosis of a postoperative pulmonary embolism and to reduce the prescription of pulmonary angiography in these fragile pts. The mechanisms responsible for these anomalies remain to be clarified.

l.Kostaoinova, Institute

Chr.Ha~jikastova

of N u c l e a r

Medicine,

~ia~ical

Academy

Uulgaria

APPLICATION

OF

99~o-HMPAO

/ Pts / WITN P U L M O N A H Y The

RADIONUCLIDE IMAGING USING XENON (133 Xe) A N D TECHNETIUM (99mTc)-LABELED MACROAGREGATES OF HUMAN ALBUMIN (MHA) IN LUNG TRANSPLANTATION PATIENTS Results of 21 s c i n t i g r a p h i e s after inhal ation of X e n o n (185 M B q - 1 3 3 X e - C I S ) and 33 scintigraphies after perfusion of MHA-99mTc (74-MBq-TCK-8-CIS) were studied retrospectively. Examinations were per-formed on 17 lung transplant patients between November 1 9 8 8 a n d F e b r u a r y 1991. Before single lung transplantation (SLT), the regional distribution of r a d i o a c t i v i t y after inhalation and perfusion provided important objective data for choosing the side of t r a n s p l a n t a t i o n . After double lung transplantation or SLT, radionuclide techniques allowed detection of p o s t o p e r a t i v e complications affecting ventilation and circulation,e.g, rejection or obliterative bronchiolitis, and were occasionally helpful in s e l e c t i n g t r a n s b r o n c h i a l biopsy sites. We have designed a specific protocol for Lung Scintigraphy in Transplant Patients (L.S.T.P.) in which lung scans performed emergently or as part of r o u t i n e follow-up are compatible with all morphologic and functional examinations used during surveillance after lung transplantation.

FP-413-1

FP-4H3-6

Sofia,

$ ¢~mmilleri*, HG Colt, F Khelifa*,L Garbe, M Noirclerc, R Giudicelli, G Kaphan* C H U T i m o n e * , C H U SUD, B l d J e a n M o u l i n , 13005 Marseille, France

lo;elisation

of

the

THROM~OCYIES

IN PATIENIS

THHOMBO[MROLIS~I source

of

the

active

throm-

b o e m b o l i s m is of a great i m p o r t a n c e for a surgical or c o n s e r v a t i v e treatment. ]he aim of the study w a ~ a p p l i n g r a o i o n u c l i ~ e laUeleo throm~ocytas, to evaluate their ~iagnostlc appliration in searching of an act±ve thromoosis in Pts with ~roved pulmonary thromboemwolism. In the all i n v e s t i g a t e d IB Pts-a i un g S ClntlIgrophy with ~gm Tc-MAA was carried out, for a l o c a l i z i n g of the area with an absent perfusion ~ a u b s e q u e n t l y - a whale Uody o c i n t i g r a p h y with "~ c-HMPAO labale~ thromuocytes. In 14 of the Pts - an increased uptake of the cells in the blood vassals of t~le lower extremities o r in the carOiac chambers was registered, ann only i n 3 Pts, there was s l i g h t l y i n c r e a s e o uptake in the big vessels of the lung. We hove consioereo, that toe reiatevely long period ~etween the onset of the oesease / f r o m 2 weeks to 2 months/and the impossibility of a cesation of the treatment with oral anticoagulants in some of the Prs at the t i m e c f invsstiqation, were the main factors, O e p r e s s i n y the active uptake of the cells in the lung. It was oonuluoeo, that this sequence of raoionucline met~oos - lung parfusion s c i n t i g r a p h y and w h o l e Ouoy s c i n t i g r a p n y with labeled thrombocytes, was a helpful strategy fat the l o c o l i z a t i o n of active t h r o m o o e m O o l i s m ann the choosing of an app r o p r i a t e treatment.

R. Bares, J. Pass, St. Hauptmann, O. Grehi, R. Reinartz, U. Buell, V. Schumpelick, C. Mittermayr. Depts. of Nuclear Medicine, Surgery, and Pathology, Technical University of Aachen, Germany MECHANISMS OF INTRATUMORAL UPTAKE OF RADIOLABELLED MONOCLONAL ANTI-CEA ANTIBODIES (MABS): RESULTS OF RADIOACTIVITY MEASUREMENTS, iMMUNOHISTOCHEMISTRY (IH), AND AUTORADIOGRAPHY (ARG) OF COLORECTAL CARCINOMA TISSUE SPECIMEN Our knowledge about mechanisms of intratumora] accumulation of radiolabelled MABs is mainly based on results of experimental studies using xenografted human tumors in n u d e m i c e . Quantitative data gained from patients, however, are rare. It was the aim of our study to provide such data, especially the amounts of specific and unspecific intratumoral MAB uptake. A total of 23 colorectal carcinomas, w h i c h had b e e n studied 4-10d earlier by immunoscintigraphy (iv administration of 0.51.0mg intact anti-CEA MAB BW 431/26 labelled with 7080 MBq 1-131) w e r e investigated after surgery. Radioactivity concentrations (RC) of ]53 tissue specimen were measured. Distribution of MAB and CEA was visualized by IH and ARG. In viable tumors m e a n RC was 7.1E03%ID/g (range 0.9-21.0). MABs were mainly localized at the tumor periphery and in perivascular areas. Positive correlations were found between RC and intensity of CEA-expression and tumor grading, a negative c o r r e l a t i o n b e t w e e n RC a n d t u m o r size. RCs in n e c r o t i c tumor tissue (12.0E-03%ID/g; r a n g e 8.0-31.4) were s i g n i f i c a n t l y h i g h e r (p<.05) and c o r r e l a t e d p o s i t i v e l y with t u m o r size, n e g a t i v e l y with g r a d i n g , h o w e v e r , no c o r r e l a t i o n was found to q u a n t i t a t i v e C E A - e x p r e s s i o n . We conclude, t h a t u n s p e c i f i c MAB u p t a k e in n e c r o t i c t u m o r t i s s u e c o n t r i b u t e s s i g n i f i c a n t l y to p o s i t i v e t u m o r c o n t r a s t used for i m m u n o s c i n t i g r a p h y . T h u s , lack of s p e c i f i c i t y of MAB a c c u m u l a t i o n m a y p r o v i d e i n c r e a s e d diagnostic sensitivity.

573

Wednesday, 4 September 1991

FP-413-2

FP-413-3

M. Deveaux, D. Poulain, C. Foueher, J. Van Cutsem, X. Marchandise M6decine Nucl4aire & Parasitologie-Mycologie, CHU Lille F Janssen Research foundation, B-2340, Beerse B

It Sai'le, M. Deveaux, E. Hachulla, J. Descamps, M. Parent B. Duquesnoy, D. Gosset, Ph. Vanhille, X. Marchandise CHU Lille - 59037 Lille Cedex - France

IMMUNOSCINTIGRAPHY IN CANDIDIASIS To determine if radioiodinated monoclonal antibodies (Mab) directed against fuugal antigens could be used to detect tissular sites of candidiasis infection, scintigraphic imaging was performed in guinea pigs infected by C. albicans. A total of 18 infected and 8 non-infected animals was used. Mab and F(ab')2 fragments directed against wall glycoproteins of C albicans were labeled with 13~I.Another Mab directed against a S. rnansoni glycoprotein was labeled with 12sIand used as a non specific control. The radiolabeled Mab were injected at a dosis of 12,5 pg and 500 kBq per animal. Images were performed 24 h later. Then, animals were sacrificed, the separated organs were gamma-counted and the number of C. albicans colony forming units (cfu) per gram were determined for each organ. A clear relationship between the anatomic distribution of C. albicans and 131Iwas evidenced. The biodistribntion of the 131I radioactivity associated with anti-Candida Mab was greater in infected animals than in healthy animals and increased with the number of cfu per g in each organ. This specificity of distribution was particularly obvious for animals with Candida endophtalmitis, a pathognomonic organ involvement following hematogenous dissemination. Distribution of the 1251radioactivity associated with the non-specific Mab was similar in healthy and infected animals in which it was independant of the intensity of the fungal parasitism. These preliminary results are encouraging enough to justify the development of a method using procedures often recommended for radioimmunoimaging, i.e. systematic use of F(ab')2 fragments and coupling with lnln. Treatments resulting from such diagnoses could improve the prognosis of these infections which is too often unfavorable.

Significance of 123I-Serum Amyloid P Component scan Amyloidosis is still diagnosed by histological examination of various organs (kidney, rectum, skin, accessory salivary glands or periumbilical f a t ) . Assessment and follow-up of systemic amyloidosis were uneasy until demonstration that 123I-SAP could be used for locating amyloidosis foci (Hawkins, N Engl J Med 1990, 11 : 329). We studied the distribution of the 123I-SAP in 12 patients and results were compared to pathological data. METHODS. SAP was prepared from pooled human sera by affinity chromatography according to De Beer (J Immunol Methods 1982, 50 : 17). 1~3Ilabeling was performed with an iodogen procedure modified from Richardson (Nuc Med Com 1986, 7 : 355). Labeling yield was better than 90 %. Final preparation of 123I-8AP was sterile and non pyrogenic. 150 MBq of ~23I-SAP (400/ug) were administered. Patients received Lugol prior to injection to avoid non specific uptake of free iodine. Anterior and posterior whole body images and regional views were acquired after 3, 24 and 48 h and activity in each organ was graded. Disappearance of circulating SAP was followed over 48 h. RESULTS. No clear relationship between the distribution of the 123Iradioactivity associated with SAP and proven amyloidosis loci could be evidenced. In 3 patients, there was no salivary uptake of SAP while salivary glands were involved in amyloidosis course. In most of the patients (8/12), splenic uptake was graded as important. Vascular activity well reflected scattered plasma clearance of SAP. CONCLUSIONS. These preliminary results are encouraging enough to justify the development of the 123I-SAP scan but more knowledge is required for a better understanding of SAP uptake.

FP-413-4

FP-413-5

W. R~mer,

R. Senekowitsch,

H. W. Pabst

Nuklearmedizinische Klinik der Technischen Universit~t M~nchen, Munich, FRG EXPERIMENTAL STUDIES ON THE USE OF ANTI-EGFREZEPTOR MAB 425 FOR TUMOR THERAPY Growth factors and their receptors are gaining considerable interest because of their involvement in oncogenesis and growth stimulation of tumor cells~ Displacement of the endogenous ligand from the receptor by an monoclonal antibody (MAb) may result in an inhibition of tumor growth. In addition a high and homogenous binding of a MAb labeled with a suitable radionuclide can lead to a successfull application for radioinununotherapy. By means of a radioreceptor assay a high density of epidermal growth factor receptors (EGF-R) on various human tumors could be demonstrated. After incubation of membrane fractions of EGF-R positive cells for 1 h using MAb 425 against the receptor in'increasing concentrations (0.3-10 nmol/l) the following binding analysis with II25-EGF s h o w e d - ~ decrease in free receptor sites by a factor of 10. If this receptor blockade is also possible in vivo an inhibition of tumor growth may be obtained. Additionally EGF-~ positive cells (A 431, Hela S3) were incubated for 48 h in a medium containing dexamethason (0.i umol/l) or TNF-~ (30 pmol/l). This concentrations are in the range of the usually applied therapeutic doses of these substances. The following determination of the receptor density revealed an increase of the recptor expression of nearly 100%. This increase in binding of a labeled MAb can lead to a successfull administration for radioimmunotherapy in EGF-R positive tumors.

574

T.Pantev, Irene Virgolini, N.Neuhold, B.Niederle, P.Angelbsrger, H.Sinzinger

Dept. of Nuclear Medicine, Vienna, Vienna, Austria

University

R E C E P T O R S FOR SOMATOSTATIN-LIKE COMPOUNDS H U M A N TUMORS IN V I T R O

of ON

The binding of tyr-3-octreotide (kindly supplied by Dr.J.Pless, Sandoz, Basel) to human tumor cell membrane fractions was determined after 123I-labeling (specific activity 1-1.6 mCi/nmol) by direct binding assaying using cold tyr-3-octreotide (SDZ-204-090) and octreotide (SMS-201-995) as agonists. Tumor tissue was obtained intraoperatively from 20 patients with different endocrine tumors (insulinoma, carcinoide, pheochromocytoma, gastrinoma,hypophysal adenoma). In equilibrium experiments, membrane fractions (40-100 #g protein/ml) were incubated with increasing concentrations of 1231-tyr-3-octreotide (0.06 - 33 ng/ml) in presence or absence of 4.8 nmol/l - 4.8 fmol/l of the agonists. Scatchard plots indicated single straight lines with binding capacities ranging from 5 to 90 pmol/mg protein (Kd from 0.5 to 90 nmol/l). The IC50 values were different (2-5 versus 3-10 nmol/l) indicating that the octreotide was a two times better competitor than tyr-3-octreotide for 123I-tyr3-octreotide binding sites.The data suggest that the 123I-tyr-3-octreotide binds with sufficiently high enough specificity to allow imaging of certain endocrine tumors in vivo.

Wednesday, 4 September 1991 - Thursday, 5 September 1991

Thursday, 5 September 1991 FP-413-6 J.c.PrrrET. D.HOFFSCHIR*, G.NORMIER**, H.BINZ**, F.DABURON*, A.LE PAPE. Laboratoire de Biophysique Cellnlaire et RMN, INSERM U 316, Tours. France. * Laboratoiru de Radiobiologie Appliqu6e, CEA-INRA Jouy en Josas. **Centre d'Immunologie et de Bioteehnologi¢P. Fabre, St Jalien en Geaevois,

FP-5D0-1 EV Dubovsky t CD Russell, M Japanwalla, M Mangipudy. University of Alabama at Birmingham Medical Center and V.A. Medical center, Birmingham, AL, USA

BILATERAL RESPONSE TO CAPTOPRIL IS NONSPECIFIC.

POTENTIAL USE OF J001 GLYCOLIPOPEPTIDE FOR THE SCINTIGRAPHIC EVALUATION OF MUSCULAR INFLAMMATORY REACTION IN A MODEL OF RADIO INDUCED LESIONS IN PIGS. Macrophages are able to interact, in vitro and in vivo, with some specific ligands from bacterial origin. This property was applied to develop a new scintigraphic strategy based on the in vivo targeting of macrophagas recruited by inflammatory lesions. J001 glysolipopeptide, (3,$ Kda, acylated peptido poly 1,3 galaetoside isolated from proteoglycans of Klebsiella pneumoniae membranes) has been demonstrated to be a potent tool for such a targeting. After labeling with 99mTc and aerosol administration, it has allowed the scintigmphic imaging of pathological lymph nodes in experimentally induced berylliosis in baboons and in cases of sarcoidosis and broncho-pulmonary tumours in humans. A model of inflammation induced by an acute local cutaneous and muscular 60 Gy gamma irradiation was developed in 6 pigs. To prevent infection and an extensive ulceration, the irradiated skin was ressected 15 days after the irradiation. Dynamic aqnisitions were performed during two hours after intravenous administration of lmg J001 labeled with 370 MBq 99mTc in the presence of 0.125 mg stannous fluoride. The intensity of the fixation was quantitated 2 hours after injection and expressed as a scintigraphic ratio: R2h=cpm in lesion/cpm in a defined healthy area in the same fimb. The scintigraphie ratios exhibited a progressive increase to reach a maximum 3 months after irradiation (R2h=3,6). Then, they decreased to recover a normal value about 6 months after irradiation. At that time of evolution. histological controls and clinical observations exhibited a significant decrease in inflammatory reaction, macrophages recruitment and apparition of fibrosis. J00l fixation was very sensitive to treatment by conicostero'fds (methyl prednisolone, 40 mg IM) that resulted in a complete clearing of the fixation 12 to 24 hours after treatment. Two weeks were then required for a complete recovery of the J001 xmagingof these lesions. So, In vivo targeting of macrophages with J001 should offer a sensitive and specific tool for the scintigraphic assessment of inflammation and possibly a new way for the pharmacological evaluation of anti-inflammatory agents.

342 captopril (25 mg) renal studies (CRS) using I131-OIH or TC-99m-MAG3 have been performed with good results in hypertensive patiests with unilateral renal artery stenosis (RAS). CRS comprised of 27 min acquisition, time activity curves and ERPF measurement. Standard criteria for positivity (+peak time, +PTT, 20 min/peak >30%) were used. 34 patients (10%) developed bilateral changes typical for RAS. 24 (70% underwent arteriography (AG)). 5 (20%) had bilateral RAS, 4 (17%) unilateral RAS, 15 (63%) were negative. We have tested several recommended methods employing Lasix (CRSL) in attempt to abolish false positive results. Out of 5 patients with positive CRS and normal AR, CRSL (injected at i0 min) yielded identical results in 4, only one patient converted to normal. Total of 14 CRSL were performed - 9 had AR, 6 CRSL (66%) were false positive, 3 (34%) were true negative. In two CRSL patients Lasix was injected with the tracer (0 time). In one patient an abnormal baseline converted to normal, in the other a false positive CRSL (i0 min) changed to normal. Neither the level of renal function (ERPF ml/min), the degree of blood pressure fall nor the status of hydration affected the results. We conclude that bilateral response to captopril is nonspecific and does not imply bilateral bemodynamically significant RAS.

FP-5DO-2

FP-5DO-3

D. Volterrani M. Carrieri, S. Ghione, L. Mezzasalma, M. Ferrari*, E. Camerini ^ and E. Fommei. C.N.R Institute of Clinical Physiology, *Department of Surgery and ^Department of Radiology, University of Pisa, Pisa, Italy.

MMC Tiel-van Buul~t GA van Montfrans 2, JA Reekers 3, A van uongen% nx uei ~. Academic Medical Center, Departments of Nuclear Medicine~ Internal Medicine 2, Ra~/odiagn0stics 3, Meibergdreef 9, 1105 AZ A~sterda~

S C I N T I G R A P H I C C A P T O P R I L TEST IN R E N A L A R T E R Y STENOSIS: AN EXPERIENCE IN ONE CENTRE. An estimation of the accuracy of the scintigraphic captopril test in the diagnosis of renovascular hypertension is difficult due to the relatively limited series of observations published. Here we report our experience in 74 patients who underwent both renal seintigraphy and angiography of the renal arteries and compare scintigraphic results with arteriographic findings and BP outcome after successful intervention. 33 pts had normal renal arteries (NRA), 29 a renal artery stenosis (RAS) greater than 50% (17 unilateral, 12 bilateral [with a stenosis greater than 50% at least on one side), 12 a RAS less than 50% (11 unilateral, 1 bilateral). Visual analysis of basal and post-captopril renographic curves was performed by grading the abnormalities of the excretory patterns (typical of RAS) from 0 to 3; (positive findings >2). True positive and true negative rate (TPR, TNR) was assessed separately on the basal and post-captopril renogram and on the changes between the two (positive change: any upgrading to grade > 2). 1. RAS >50%: TPR: basal = 52%; post captopril = 93%; changes = 57%; NRA: TNR: basal: = 88%; post captopril = 85%; changes = 97%. Out of the 5 false positive pts, 4 were abnormal (unilaterally) both basally and post captopril, and 1 became so only after captopril (bilaterally). 2. BP outcome after intervention: 20 pts underwent technically successful interventions (PTA or by-pass). Pre-intervention post captopril renograms were positive in all 15 pts who were cured and in 3 who were not cured. These results confirm that this test is an accurate means for the detection of angiographically relevant RAS. The strong correlation between scintigraphic results and BP response to intervention points to this technique as a first choice tool for the non invasive diagnosis of renovascular HT.

CAI>IOPRIL RENOGRAPHY WITH 99m-Tc-MAG3 IN THE DIAGNOSIS OF RENAL ARTERY STENOSIS: TES%L"RITERIA AND INTEROBSERVER VARIABILITY. To assess the test characteristics and interobserver agreement of Ca/pto~ril ReD~ography (CR} . with 99m-Tc-MAG3 u s i n g p r e a e ~ i n e a criteria, we examlnea a consecutive series o f 60 Datients (M/F=37/22, mean age 45. 4 years, range 14-74]. qhey eitner had treatment-resistant hypertension ~HT) or severe untreated HT. Diuretics and ACE inhibitors were uspended for at least one w e e k After an overn/ght ast, renal scintlqraphy (RS) before ana one nour after administration o f 25 mg captopril orally was performed. ~or each renograpny the patien~ was h ~ t e d orally with 500 ml water. Two nuclear medicine physicians inaepenuenv_Ly assessed the rena~ seintig-~-ams. '±he test was znterpreted as positive if unilateral changes in v/le renogram after captopril were seen (Time to Peak > i m/n or Relative Excretlon Rate > 2. i). The agreement between the onservers was cnaracterized by k a p ~ statistics. With/n 15-30 days all patients underwent renal arterioc~_pny according to ~IdiI~ge~ s technique. Results: 46/60 pa_~ients had no stenoels [n=39) or stenosis <50% (nl-7). 14/60 patients had unilateral (n=ll) or bilateral (n=3) s~enosis >50%. BS showed a sensitivity (TPR) of 41%, sDeciflcity (TNR) 86%, positive predi"ctive value (PV+) 33 % ~ negative predictive value (PV-) 90%. The combination of RS and CR increased TPR to 47%, TNR to 97%, and PV+ to 73%. PV- was 92%. Interobserver agreement beyond chance was 65 % in scinti~ without ca~to~gil,, whereas a¢[reement beyond cnance increased to 99~ when r_ne eombinea renograph~ was taken into consideratior~ In c o n c l u s i o n w e f o u n d that in the. diagnosis of renal artery s~enoszs ~ as we-- as ~K snow gooa inte.robserver agreement. However~. in our hands sensitivity wa@. -ow ~ specilici~y was high, making rme proceaure -ess suitable as a screening method to detect renal artery stenosis.

~

575

Thursday, 5 September 1991

FP-5D0-4

FP-5DO-5

J Boman~, KB Britton, CC Nimmon, B Birkenfeld, S Yasmeen, A A1 Awadhi. K, Singh, RF Jewkes. St. B a r t h o l o m e w ' s Hospital, C h a f i n g Cross Hospital, London.

E. Pommel, S. Ghione, L. Mezzasalma, D. Volterrani, M. Carrieri. C.N.R. Institute of Clinical Physiology, Pisa, Italy.

CAPTOPRIL, M E A N P A R E N C H Y M A L T R A N S I T TIME, MPTT, A N D R E N O V A S C U L A R D I S O R D E R , RVD. The detection of RVD depends on demonstrating its pathophysiological changes. T h e s e m a y be e n h a n c e d by p r i o r Captopril. M P T T is p r o l o n g e d over 240s in RVD (AI N a h h a s et ai.1989). This study e x p l o r e d the e f f e c t of C a p t o p r i l on M P T T in a p i l o t study. 13 p a t i e n t s t h o u g h t l i k e l y to have RVD w e r e i n v e s t i g a t e d b e f o r e and a f t e r 25mg C a p t o p r i l u s i n g 120MBq T c - 9 9 m MAG3 w i t h m e a s u r e m e n t of r e l a t i v e function, RF, M P T T a n d o u t f l o w e f f i c i e n c y , OF. Six p a t i e n t s w e r e c o n f i r m e d to h a v e RVD, in these RF d e c r e a s e d by over 15% in three, w i t h no c h a n g e in three. M P T T was p r o l o n g e d in all (mean 298s) b e f o r e C a p t o p r i l and further i n c r e a s e d by it in all (mean 443s). OF s h o w e d no c o n s i s t e n t change. In ? p a t i e n t s w i t h o u t RVD, RF c h a n g e d by less than 15% and M P T T s h o w e d no c h a n g e or a fall in all a f t e r Captopril, from a m e a n of 211s to 182s. M P T T a p p e a r s to be a s e n s i t i v e m e a s u r e of RVD and C a p t o p r i l e n h a n c e s this.

A1 N a h h a s A, M a r c u s AJ, B o m a n j i J, Nimmon CC, D a c i e 3E, B r i t t o n KE. V a l ~ d i t y of the Mean Parenchymal Transit Time in Renal A r t e r y Stenosis. Nucl Med C o m m u n I0, 80?815 (1989),

FP-5H0-1 S. DE MAEGHT, L. LAMBOTTE, T. VANDER BORGHT, S. PAUWELS Centre de M~decine Nucl~aire, Unit~s de Chirurgie Exp. et Gastro-ent~rologie, University of Louvain Medical School, avenue Hippocrate 54, 1200 Brussels, Belgium.

CONTRIBI/TION OF LAB~N.RDC% TO PET IMAGES OF TH~ LIVER ~TI] [2-11C]TIPII~DINE (TDR). Previous rat studies have shown that hepatic cellular proliferation can be evaluated by PET using [2-ZzC]Tdr. It has been suggested that accumulation of 1zC02, a metabolite of [2-zZC]Tdr, could significantly contribute to the PET images. Therefore, we have now studied the blood and hepatic retention of 14C02 after injection of 10~Ci [2-z4C]Tdr in 19 rats with regenerating liver (RL) and 34 controls (NRL). Rats were killed after i0 to 120 min and whole blood and liver samples were immediately homogenized in 1.5M perchloric acid, the total volatile fraction being continuously trapped in 3.3M ethanolamine. The amount of blood and liver 14C02 (dpm/g tissue) decreased with time as followed : 1Omin 3Omin 6Omin 90min 120min blood NRL_ 18300 16400 1010O 5500 2500 RL 17400 17200 7700 3200 2700 liver NRL 13700. 9100 4000 2100 700 RL 22600 14800 6500 2500 1800 In NRL and RL, z4C02 expressed as a % of total Z~C remained elevated in blood throughout the study whereas it rapidly 'decreased in the liver accounting for only 10% of total 14C in NRL and 4% in RL at 90 min. In NRL rats, a positive correlation was found between blood and liver total Z4C (r=O.87; p< O.O01), and between blood and liver 14C% (r=0.94; p<0.OOl). Our data suggest that labelled CO 2 would only play a minimal part in total hepatic radioactivity measured 90 min after injection of Tdr labelled in C-2 position. In addition, the correlation between blood and liver activity found in controls, could be useful in vue of a more accurate quantification of the true [2-ZIC]Tdr hepatic uptake.

576

on behalf of the C.R.T. European Multicentre Study. CAPTOPRIL RADIONUCLIDE TEST IN RENOVASCULAR HYPERTENSION. The final results of the European Multicentre Study on Captopril Radionuclide Test will be presented at the meeting. - Participant centres: R. Baum, Frankfurt, FDR; I. Beuerlein, Hamburg, FDR; E. Brianzoni, Macerata, Italy; M. Dondi, Bologna, Italy; E. Fommei, Pisa, Italy; M. Fraile, Barcelona, Spain; M.J. Goggin, Canterbury, United Kingdom; D. Granjon, S. Priest en .larez, France; R. Hoschl, St. Leonards, Australia; G. Jensen, Gtkeborg, Sweden; P. Jezersek, Ljubljana, Yugoslavia; E. L~insimies, Kuopio, Finland; R. Mtiller-Suur, Danderyd, Sweden; H. Y. Oei, Rotterdam, The Netherlands; A. Piepsz, Brussels, Belgium; M. Poropat, Zagreb, Yugoslavia; C. Proukakis, Athens, Greece; C.G. Santos, Porto Alegre, Brasil; J. C. Wautrecht, Brussels, Belgium. - Executive Committee of the study: E. Fommei (Pisa, Italy), S. Ghione (Pisa, Italy), I. Gordon (London, UK), A.J.W. Hilson (London, UK), H.Y. Oei (Rotterdam, The Netherlands), A. Piepsz (Brussels, Belgium). - Central Office: Institute of Clinical Physiology, Pisa, Italy. Period of data collection: September 1987-June 1990. Final data after quality control. Patients: 426 pts, 195 without and 229 with renal artery stenosis. Tracers: 349 DTPA, 28 Hyppuran, 66 MAG3 studies. Interventions: 70 PTA, 38 By-pass, 6 nephrectomies. Follow-up clinical data: 80 at 3 months, 50 at 6 months, 29 at 12 months.

FP-5H0-2 W. Burehert. *O. Selberg, G.J. Meyer, *M. J. M011er,H. Hundeshagen Dep. Nuclear Medicine and *Gastroenterology Medical School Hannover, Germany GLUCOSE UTILIZATION OF THE SCELETAL MUSCLE IN PATIENTS WITH LIVER CIRRHOSIS DETERMINED BY POSITRON-EMISSION-TOMOGRAPHY (PET) Up to 70 % ofpatients with liver cirrhosis have clinical signs of malnutrition. To analyse the quantitative properties of the impaired glucose metabolism 6 cirrhotic Lots.and normal volunteers were investigated. The total glucose utilisation and the total glucose oxidation rate ot the body were mearsured by clamp technique and indirect calorimetry, To define the regional glucose utilization of the sceletal muscle serial PET scans were aquired by a Siemens ECAT 951 after injection o1370 MBq 18-F-FDG under clamp condition. Axial slices of the upper thigh were dynamically measured during 50 minutes. Pseudoartedal blood samples (heated hand) were taken according to the frame rate to provide dynamic analyses of the glucose uptake. The quantiticahon was based on the usual three compartment model of FDG. The glucose utilization rate was determined by the graphical Patlak-Piot analysis, A lumped constant ol 0.67 was assumed 1. Under clamp conditions the cirrhotic patients showed a metabolic rate of glucose of 4.4 p.mol/100g/min compared with 7.5 p.mol/100g/rain of normal volunteers. A good correlation of total sceletal muscle glucose utilization was found between two methods: First the local metabolic rates (PET) times mass of sceletal muscle of the body (ereatinine excretion) and second the known fraction of the scelatal muscle in total body metabolism times the measured total glucose utilization. The data suggest that the determination of the glucose utilization of the sceletal muscle in vivo is a reliable tool in analysing different causes of impaired glucose metabolism, e.g. in liver cirrhosis and the early postoperative period. 1 Ratib O, Phelps ME, Huang SC, Henze E, Selin CE, Schelbert HR. Positron tomography with deoxyglucose for estimating local myocardial glucose metabolism. J Nucl Med 1982; 23: 577-586.

Thursday,

FP-5HO-3 Ehrenheim Ch, Petarsen H, Knshans A, 8rstz KF, Klempnsuer J, Wetmenn A, HundeshagenH. Department of Nuclear Medicine end Clinic of Abdominal Surgery, MedicalSchselof Hennover,FR8 CAN DYNAMIC CONTRAST-ENHANCEDMRI IHPROVE THE DIFFERENTIATION OF FOCAL LIVER LESIONS ? PATIENTSAND METHODS:35 patientswith liver tumors (hemangioma, focal nodular hyperplasia FNH, hepatacellulor carcinoma HCC, metastases) underwent dynamic MRI of the liver in addition to scintigraphic sequential imaging methods (HBS5, RDC scan using Tc-99m-labeled erythrocytea). Dynamic MR studies were performed using a gradient echosequence(FLASH) during i.v. bolus injection of 0,2 ml/kg Oadolinlum-DTPA. Two different dynamic studies wlth various delay times were applied depending on the presumptive diagnosis. Conventional11 - end T2-weighted imageswere acquired, as well. RESULTS: Oheract~ristic kinatics and uptake patterns ware found in dynamic MRI: Liver hemsngiomas show the most intensive uptake of 8d-DTPA. In the dynamic study the negative tumor-liver contrast first increa'~=s,and aub~quentlythe losionshowsa delayedosntripetal filling in. This facilitates the differentiation hemangioma/malignanttumor that may appear similar in native images.The demarcationof FNH is usually nat influenced by late contrast-enhanced images, although dynamic MRI revesls the characteristic hyperperfusion. Nevertheless, HBSSseemsto be rnor~ ~nsitive. Finally, Od-DTPA pre~nts a mixed pattern of uptak~ and distribution in HCCand metastaseswith hyperperfusion as a common finding. Combined with the post contrast images that usually show a moderate inhornogeneous ¢nhancerncnt MRI is superior to the scintigraphic methods applied in the differentiation of these malignant lesions. CONCLUSIONS:Dynamic MRI is useful in the diagnosis of liver tumors and

improvesthe differentiationof focal lesions.

5 September

1991

FP-5HO-4 Barbano F°, Petracca Ciavarella G., Annese V., Modoni S., Frusciante V., Perrone E,, Valle G., Varraso A. Depts. of Nuclear Medicine and Gastroenterology Hospital C.S.S., S. GiovaDni ~otondo (Fg), Italia 123-1-1NSULIN SCINTIGRAPHY IN LIVER DISEASES 123-l-bovin insulin, labelled on tyrosinic fragment 14 inside A chain, allowed us to evaluate its biodistribution and metabolic pathway. In our study we searched quantitative indexes derived from insulin imaging in different groups of diseases. Overall 68 subjects were evaluated: A)20 pts. with liver cirrosis; B)I5 pts. with cirrosis and diabetes mellitus; C)6 pts. with cancer and cirrosis; D)6 diabetic insulin-resistant pts E) i patient with liver radiation hepatitis; F) 20 subjects as a control group. Patients were administered 74 MBq 123-I-insulin. Dynamic study was performed by acquiring 15 see. frames for a total period of 38 mins.We computed various indexes from liver curves: Tmax, TI/2 and T75-75. Statistic analysis was performed by t Student test for unpaired data. The T75-75 index seems to be more useful to express the contemporary happening of hormone-receptor interactions, complex internalization, and 123-I extrusion from the cells as a consequence of insulin cathabolism. Results (m±sd): group A B C D F T75-75 17.23±3.6 13.82±2.3 14.3±2.8 16.2±3.9 I0.3±0.9 vs. gr.F p<0.001 p<0.001 p<0.001 p<0.001 Cirrotic patients (gr. A) have a T75-75 value different from clrrotic-diabetic (gr. B) patients (p<0.02), This result shows that the metabolic destiny of insulin is in any case worse in the diabetic-eirrotic liver than in the eirrotic liver of non diabetic patients. Moreover, the high transit time in insulin-resistant diabetic (gr. D) patients and in the only one patient with radiation hepatitis (gr. E) provides an useful quantitative index for the same insulin resistance.

FP-5HO-5 H.Bihl, Monika Sterz,*H.M~cke, ~M.Eisenhut, ~U.R~th Klinik fur Nuklearmedizin, Katharinenhospital Stuttgart, Universities of ~Basel Switzerland, #Heidelberg, FRG

SOMATOSTATIN RECEPTOR SCINTIGRAPHY: A NEW SCINTIORAPHIC TOOL IN THE MANAGEMENT OF INTESTINAL CARCINOIDS ? Intestinal careinoids (ICs) are known to express a large number of binding sites with high affinity for somatostatin (SMS). Different SMS analogs have been developed (Sandoz, Switzerland) which proved to possess a similar affinity to these SMS receptors (SMSRec) as the native SMS. It is only recently that the Rotterdam group, the Netherlands, reported successful use of one of these SMS analogs, the radiolabeled SDZ204-090, in the in vivo localization of SMSRec-positive tumors. We present prelimina~j data on in vivo SMSRec scintigraphy with this SMS analog in i0 patients with known IC (5 pts with primary tumor PT, 7 pts with liver metastases). After adequate blockage of the thyroid 120-200 MBq 1-125 labeled SDZ204-090 were injected intravenously. The 1125 labelling was performed following the original description of the Rotterdam group. Planar images were made (Orbiter o r Bodyscan/Siemens) in the following manner: 1 frame/min for the first 30 min.; static scans at 0.5, 2-4, sometimes 24h p.i. Results: SDZ204-090 is rapidly cleared from the circulation via kidneys and liver, immediatly followed by hepatobiliary excretion. Serum half-life is about 2-4 min. The in vivo localization of SMSRec-positive ICs with SDZ204-090 takes place early after i.v. administration: The 3 PTs could be visualized as early as 10-15 min p.i. In the seven pts with liver metastases six pts showed at least one metastasis, in three pts of this group further liver metastases were hidden by gallbladder activity. Conclusions: These preliminary data show that 1-125 SDZ, 204-090 is a promising agent for a quick in vivo localization of ICs. Clinical indications fo~ SMSRec-scintigraphy may be: (1)staging of ICs, (2)in vivo examination for SMSRec-positivity of ICs, the latter being mandatory for the successful s.c. SMS-therapies.

577

Monday, 2 September 1991 Monday, 2 September 1991 PO-2L1-1 E Delcourt, C.H.U.

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J-P Binon, R Amir

A. VESALE

6110 M o n t i g n y le Tilleul, B E L G I U M

A.Jim@nez-Heffernan, F.M.Gonz~lez, J.L.Villanueva*, A.Moral, A.Valverde, M.Torres, J.M.Latre, J.M.Llamas, A.Mateo Serviees of Nuclear Medicine and Internal Medicine*, Hospital "Reina Sofia". CSrdoba. SPAIN

ACCURACY AND PRECISION OF LUMBAR DUAL PHOTON A B S O R P T I O M E T R Y M E A S ~ R E D W I T H THE SCINTII~LATION C A M E R A

We have t e s t e d in c l i n i c a l c o n d i t i o n s the v a l i d i t y of B o n e M i n e r a l D e n s i t y (BMD) or C o n t e n t (BMC) measurements obtained with the scintillation camera t e c h n i q u e (SCT) as an a l t e r n a t i v e to d e d i c a t e d d u a l photon absorptiometry (DPA) equipments. The method uses a convergent c o l l i m a t o r and a source of Gadolinium. C a l c u l a t i o n a l g o r i t h m s are similar to those used in usual DPA. We have d e v e l o p e d a processing in which the regions of i~terest are drawn semiautomatically, hence reducing operator intervention and inter-observer variability. BMC accuracy was t e s t e d in p h a n t o m studies. Two b o n e p i e c e s were i n d e p e n d e n t l y m e a s u r e d 28 times each. The a v e r a g e BMC v a l u e s of the p h a n t o m s w e r e compared w i t h t h e t r u e BMC v a l u e s o b t a i n e d f r o m t h e n e u t r o n a l act i v a t i o n t e c h n i q u e (NAT). R e s u l t s are e x p r e s s e d as the r e l a t i v e d i f f e r e n c e (%) b e t w e e n the r e f e r e n c e N A T value and the m e a n of the 28 BMC v a l u e s obtained w i t h SCT. BMD p r e c i s i o n was t e s t e d in clinical conditions: six normal volunteers, i n c l u d i n g 3 u n s e l e c t e d patients and 3 m e m b e r s o f the d e p a r t m e n t staff, were i n d e p e n d e n t l y studied in 4 separate instances. Results are e x p r e s s e d as the m e a n of t h e r e l a t i v e s t a n d a r d d e v i a t i o n s , which are in e a c h p a t i e n t t h e r a t i o of the s t a n d a r d d e v i a t i o n to the m e a n of the 4 BMD measurements. Results: P h a n t o m studies: Accuracy 1 SCT = 1.165 (SCT - N A T ) / N A T = 1.30 % 2 SCT = 1.279 (SCT - N A T ) / N A T = 6.69 % > A v e r a g e = 4.00 % P a t i e n t studies: Precision Patients: M e a n BMD = 1.037 M e a n (SD / X) = 3.62 % M e a n (SD / X) 3.17 % Dep.staff: M e a n BMD = 1.033 > Average

= 3.40 %

We conclude that the SCT a p p l i e d to D P A m e a s u r e m e n t s y i e l d s b o t h a c c u r a c y and p r e c i s i o n w h i c h are in t h e same range as t h o s e r e p o r t e d for d e d i c a t e d e q u i p m e n t s in clinical conditions. Therefore, SCT is a p r a c t i c a l a l t e r n a t i v e in n u c l e a r m e d i c i n e d e p a r t m e n t s w h i c h are o n l y m a r g i n a l l y c o n c e r n e d w i t h BMD measurements.

~,UMaN POLYCLONAL IgG-99mTc (HIG) IN THE STUDY OF INFLAMMATION/INFECTION OF BONE AND SOFT TISSUE. We studied the behavior of HIG in 24 patients (pts) referred to us because Of the following conditions: suspicion of osteomyelitis (0M)(9),fever of unknown origin (FU0)(7), lung/pleural inflammation (5), vascular graft ~nfection (i), and brain and liver abscess in one case each. Imaging was performed at 6 and 24 hours post-injection of 740 MBq of 99mTc-HIG. At 6h imaging included thorax abdomen and pelvis in anterior and posterior views at " i06 counts as well as limb and head views if lesions were sus. pected in these areas. At 24h only the suspicious areas were imaged at 5x105 counts. HIS was positive in 5 cases of proven 0M and negative in 4 cases of noninfectious bone disease, therefore yielding excellent results. In pts with FU0, HIG was truly positive (TP) in one case; falsely negative (FN) in 2 cases (phlebitis due to S.epidermidis, and basal pneumonia) and truly negative (TN) in the rest. In the lung disease group HIS yielded FN images in a p t with proven empyema due to various microorganisms. Of interest are the cold images obtained in 2 pts with lung and liver abscesses. HIG was negative in a cerebral toxoplasma abscess after 2 weeks of treatment. In the vascular graft HIG was TN. We think HIG is well suited for bone infection detection with high sensitivity and most importantly high specificity. Its role in FU0 is yet to be determined and it yields some FN results in lung/pleural infections. Visualization of colonic activity in 2 pts that washed out after enemas may preclude intestinal inflammatory disease assessment with this new agent.

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M. I . i b e r a t o r e , M . C l e m e n t e , A.P. Iurilli,L. Zorzin*,M. Marini*,E. D i R o c c o , A. C e n t i C o l e l l a Section of Nuclear Medicine,Dpt.of Experimental Medicine and *Institute of Reumathology, University "La Sapienza", Rome, Italy

G Madeddu,F []ore, GC Melis, E Ftmu, A Arru, ND Azzena, AR Casu. Department of Nuclear Medicine; University of Ssssari - Italy.

SCINTIGRAPHY IN REUMATHOID AND PSORIASIC ARTHRITIS (RPA): A COMPARISON AMONG LABELLED LEUKOCYTES,NANOCOLLOIDS AND HUMAN ASPECIFIC IMMUNOGLOBULINS The 99mTc-labelled aspecific policlonal immunoglobulins (HIG) is a n e w r a d i o p h a r m a c e u t i c a l which seems to be able to localize the sites The aim of this work is to of inflammation. evaluate the clinical usefulness of this tracer in R P A b y a c o m p a r i s o n with 99mTc-HMPAO Leukocytes(WBc)and 99mTc-labelled nanocolloids (NC). 17 p a t i e n t s affected by relapse of RPA the number and were studied. In each patient sites of joint inflammation were assessed by All patients underwent clinical examination. scintigraphy with HIG. Scans with WBC were ( g r o u p i), m e a n w h i l e c a r r i e d o u t i n i0 p a t i e n t s 7 patients (group 2) were studied by NCscintigraphy. The results of the comparison between scintigraphic and clinical examination a r e s h o w n in t h e f o l l o w i n g table: +scans/+clinical e x a m i n , (n ° o f j o i n t s i t e s ~ Group 1 Group 2 HIG=40/41 WBC=25/41 HIG=34/35 NC=33/35 -scans/-c]~nical examin.(n ° of Joint sltes~ Group 1 Group 2 HIG=33/41 WBC=38/41 HIG=36/49 NC=41/49 The HIG scintigraphy seems to be more sensitive than WBC and NC scan to detect sites of joint inflammation. However some positive HIG scans were observed in c l i n i c a l l y negative joints: a clinical follow-up is m a n d a t o r y in o r d e r to explain these results.

578

SCINTIGHAPHIC AND ABSORPTIONETRIC PROCEDURES IN TP~ EVALUATION OF CARBOCALC~ (CTE) TREATMENT IN REFLEX SYMPATFETIC DISTROPHY S]~RO~ES (RSDS) Radioisotopic procecha~s were fctmd to be useful for disgrmsing and mcnitorir~ therapeutic response in RSD$. To further investigate their role we studied 24 patients affected by post-lratmatic RSDS with involvement of the upper extremities,following homerus fractures. In all of these we measured bone mineral density (BMD, mg/cm2) by dual photon absorpticgetry (N/~) in distal radius beth in affected end normal cor~trolateral ex~ities. The patients then usder%~nt dynanic and static ecintigraphic tests after i.v. injection of 99mTc-JDP (20 mCi) with the collimator of garma camera centered in both extrsmities.Three days later delayed static images were registred 30' after 99mTc-nanocolloid (i0 mCi) injecticn; this tracer can be useful for detecting inflam~tion. BMD values were significantly (p~0.001) lower in the affected sides (318.4 +- IS2.4 mg/cm2)'when corspared to normal controlateral cries (38a.8 + 137.2 mg/cm2). Time activity curves with NDP showed a higber flow in the involved extremity.A significant increase of the blood pool and. pf the bone uptake was also noted. Moreover, 99mTc nenccolloid uptake showed a significant increase in affected sides.After CTE treatment (80 U/q.d.i.m. in 12 cases end 40 U/q.d i.m in the other 12 cases for a month) all the patients presented the improvement of clinical s/mptc~s and a significant increase of BND that was bnsnght into normal r~-ge in 7 of the patients who had a icier treatment (40 8/q.d. i.m. for 2 n~nths). Both local blood flow and bone uptake in the affected side significantly decreased after CTE while bone avidity index Increased in respect of the acute phase in those patients in whom this parameter had been measured (3.93 + 3.70 v.s. 1.28 + 0.22; p~:0.05). The decrease was also sigr/ficant in colloid static imsges.0ur data confirm the usefulness of radioisotopic proce~ in Dost-traumstic }%~33 both in diagnosis,by demostrating Increased local blood flow,early bone demineralizatien end inflammatory associated processes,as well as in monitorir~ resp
Monday, 2 September 1991

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P Martin, M Verhas, C Als, J Paternot and P Bergmann. Dept Nucl Med, Brugmann Univ Hospital, 4 pl. A Van Gehuchten, 1020 Brussels, Belgium.

WJG Oyen, IE Arntz, RAMJ Claessens, DJMJ Immerzeel, JWM van der Meer, RJA Goris, and, FILM Corstens. University Hospital Nijmegen, Dpts. of Nuclear Medicine, Surgery , and Internal Medicine, Nijmegen, The Netherlands.

BONE MINERAL DENSITY (BMD) AFTER ESTROGENS OR FLUORIDE THERAPY IN POSTMENOPAUSAL WOMEN. We measured BMDbefore and after estradiol or fluoride therapy in 3 groups of postMNP women: 40 women (57 _+5 y)" without crush fractures treated with estrogens (gr.l), 10 women (55 ._+4 y) with vertebral crush fractures treated with estrogens (gr.2) andl8 older women (68 _+7 y)with crush fractures treated with NaF (gr3). 'Ihey were seen sequentially up to 36 months. A monthly increment was calculated as I(g@= BMD (time'I) - BMD (To)/months. Sites of measurement included the radius (metaphysis, shaft) (M#Isgaard BMA1100, arbitrary units) and lumbar spine (I.2-L4) (Novo Lab 22a, g/cm2). Results: ! BMDpre [ BMDore (M') I_ BMDpre (S) arbitrary units % a:u. % (L2-L4)g/cm 2 % Grl 1,2+0,2 0,22 1,8+0,3 0,09 0,8+0,1 0,29

DETECTION DYSTROPHY MOWSPECIFIC

Gr2

1,1+0,3 0,27 1,8+0,3 0,05 0,67+0,1 0,43 n.s. n.s. p<0,005 Gr3 0,84+_0,2 0,22 1,34+--0,4 0,09 0,64+_0,16 0,68 p<0,001 p<0,00l p<0,00t At lumbar site, a negative correlation existed between the monthly increment and BMD before treatment: I= 1,23-1,2 BMD (r=0,55, p<0,001 ) (gr.1), I=2,4-3 BMD(r=0,67, p<0,001) (gr.2) and I= 1,8- 1,8 BMD (r=0,53, p<0,001)(gr3). No significant relation was found at radial sites. (bnclusions: At lumbar site, BMDis significantly decreased in gr. 2 and 3 as compared to gr.1. It is not different in gr2 at radial sites but well in gr3, in an older population. "lhe increment is more important in regions rich in trabecular bone.'lhe negative relationship between increment and BMDcould be due to the fact that in case of important bone loss, the greater mechanical stress on remainig bone could induce a more important response to treatment.

OF INFLAMMATION ~M REFLEX SYMPATHETIC (RSD) WITH INDIUM-111 LABELED HUMAN IM~F~NOGLOBULIM G (In-111-IgG) SCINTIGRAPHY.

RSD is a serious medical condition, that can occur in the upper or lower extremity after relatively minor surgery or t~auma. It may lead to severe pain in the affected extremity and loss of function. Since the classical symptoms of inflammation are present in the acute phase of RSD, Sudeck hypothesized an excessive inflammatory response to injury. Presently it is assumed that RSD is caused by an abnormal reflex of the sympathetic nervous system. In this study the inflammatory component of RSD was assessed with In-lllIgG scintigraphy, a relatively new technique to evaluate inflammatory processes. Twelve patients with RSD of the upper extremity were studied. Irmmediately after intravenous administration of 75 MBq In-lll-IgG dynamic images were obtained. Static images were obtained 5 min., 20 min, and 4, 24 and 48 hours after injection. Focally increasing activity over time indicated increased extravasation of In-lll-lgG and was considered to be indicative of inflar~nation. In 6 of 8 patients suffering from RSD for less than 5 months, a positive In-lll-IgG scintigraphy was found. In contrast, only 1 of 4 patients with RSD existing for more than 5 months had a positive In-lll-IgG scintigraphy. None of the non-affected extremities showed any abnormal uptake. We conclude that - in contrast with current consensus a prominent characteristic of inflammation i.e. increased vascular permeability is present in early RSD. Further studies are necessary to evaluate whether presence or absence of In-lll-lgG accumulation has any significant predictive value on the outcome of a therapeutic regimen.

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Castelo-Branco C, P o n s F*, F u s t ~ P, M a r t i n e z de O s a b a M J ' , P a l a c i o M. G o n z ~ l e z - M e r l o J. Dept Obstet & Gynecol, * Dept Nuclear Med. Lab Hormons. Hospital Clinic de Barcelona.

J. Roland, L. Williame, P. Herregods, R. Chappel, J. Vandevivere. Middelheim General Hospital, 2020 Antwerp, BELGIUM.

Effectiveness of four hormone replacement therapy (HRT) regimens as assessed in postmenopausal women by dual photon absortiometry. A total of 84 postmenopausal women were randomly assigned to 4 groups: G r o u p i: 20 w o m e n w h o r e c e i v e d 0 . 6 2 5 m g / d a y of Conjugated Equine Estrogen (CEE) cyclically (25 d a y s / m o n t h ) . G r o u p 2:23 women who received 0.625 mg/day of C E E c o n t i n u o u s l y . (each day/ m o n t h ) . G r o u p 3: 17 w o m e n w h o r e c e i v e d 50 ~ g / d a y of t r a n s d e r m a l 17-B-Estradiol cyclically. (24 d a y s / m o n t h ) ( T T S ) . G r o u p 4: 24 w o m e n w h o did not take any treatment. All treated groups received 2 . 5 m g of M a e d r o x i p r o g e s t e r o n e Acetate sequentially f o r t h e l a s t 12 d a y s of H R T . Dual photon absortiometry was carried out befo re t h e r a p y and repeated a f t e r 1 y e a r in a l l t h r e e t r e a t m e n t g r o u p s a n d in c o n t r o l g r o u p . T h e c h a n g e in b o n e m i n e r a l c o n t e n t (BMC) w a s : BMC C E E c y (i) C E E co (2) TTS (3) Control(4) |

p <0,01

basal

i,i12 1,070 1,039 1,154 *

~ ± ± ~

0,153 0,157 0,185 0,171

p < 0,05

BMC

1 year

1,126 1,109 i,ii0 1,123

± + ± ±

%

0,189 1,3 0,152". 4,4 0,193 * 7,1 0,157" -1,5

2 - 4 3 - 4

In c o n c l u s i o n , TTS was found to be effective for bone maintenance producing unexpectedly large increase

p < 0,05 p < 0,01

A COMPARISON OF A DUAL HEAD VERSUS A THREE HEAD GAMMA CAMERA IN THE DETECTION OF BONE LESIONS OF THE SPINE : ARE SYSTEMATICAL TOMOGRAPHIC ACQUiSITiONS USEFULL ? Since tomographic acquisitions are rather time consuming, we wanted to evaluate if it is usetuil to perform systematically tomographic acquisitions of the lumbar spine, even if the planar bonescintigraphy is normal. Patients, referred for the investigation of low back pain as well as those referred for the investigation of metastasis were entered in the study. All patients underwent a planar bone scintigraphy, using a dual head gamma camera (Siemens, Whole body), three hours after the injection of 900 MBq of Tc-99m MDP. If the planar images could not reveal bone lesions of the spine, we performed a tomographic acquisition of the lumbar spine ( total acquisition time 25 minutesl, 3° projection images, ultra-high resolution collimator) using a three head gamma camera (Trionix, Triad). Images were reconstructed into a 64X64 matrix using a filtered backprojection algoritm (Hamming filter, cutoff frequency of 1 cycles/cm). If possible, the tomographic acquisition was performed on the same day as the planar images. In this way 40 consecutive patients with a normal planar bone scintigraphy were evaluated. The tomographic images revealed bone lesions in 60 % of the patients with low back pain, even if the planar bone images were normal. Most lesion were either Iocalised behind the corpus vedebrae or between 2 vertebras, corresponding with active bone formation in longitudinal ligaments. The tomographic images revealed bone lesions in 40 % of the oncological patients, even if the planar bone images were normal, in half of the patients this finding had therapeutical consequences. in conclusion, we can say that, although it may be time consuming, if is advocated to perform systematically tomographic acquisitions of the spine even if the planar images are normal.

the more and for in B M C

579

Monday, 2 September 1991

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L.Rosenthall, M. (lhazal, E.Brooks. McGill Universitv, Montreal General Hospital, Montreal, Canada

J. Spitz, H. Becker, H. Weigand, K. Tittel. Municipal Hospital, Wiesbaden, FRG

NORMAL T~IMPORAL UPTAKES OF MDP ADJACIgZf TO THE ACETAB~ AND FEMORAL C O M ~ S OF POROUS-COATED HIP PROSTHESES The MDP concentrations in bone adjacent to a porouscoated AML (TM) hip implant in a s ~ t o m a t i c patients were determined as a function of time. The median Harris hip score for function was 94. 62 hips were studied with implants of 1.6 to 49 months duration. Numerical ratios of the uptake in the superior, middle and inferior acetabular zones to the reference sacroiliac joints(SIJ) were obtained with ccmputer assistance. Similar ratios were procured for the fenDral stem, greater trochanter, lesser trochanter and calcar, stem h i p a n d normal femur. Stem tip/stem, and stem/(normal fe~mlr) in unilateral ir~olants, were also derived. The moans of all ratios for implants less than 12 mo. were significantly greater than those 12+ mo. of age, except for the normal f 6 ~ r / S I J ratio. In the 12+ age group there was no correlation between the various ratios a n d t h e age of the implant, indicating a stabilization of bone remodeling after one year. Two exceptions were stem tip/stem and lesser trochanter/SIJ, which showed a w e a k b u t significant decrease with age. The former declined 24% between 12 and 49months. These nornml MDP uptake ranges are vet to be proved of value i n t h e disclosure of ir~lant icosening,-andthere is evidence that differently designed porous-coated ir~plants may have different means.

PATHOPHYSIOLOGY OF BONE REMODELING AFTER TRAUMA OF THE LIMB, DEMONSTRATED BY SCINTIMETRY WITH TC-99m-HMDP.

This study was done, to evaluate the different factors, which are responsible for the time depending changes in the scintigraphic appearance of fractures of the limb. Material and method: 120 patients after a trauma of the wrist (68 fresh fractures, 40 soft tissue lesions and 12 miscellaneous lesions) and 30 patients from oncologic follow-up as "normals", aged 18-72 with equal sex distribution were investigated by 3-phase-scintigraphy with TC-99m-HMDP (CIS-International) on a digital gamma-camera (APEX 415) 1-700 days after the accident. RESULTS: The quantitative analysis of the results showed the following factors, leading to the typical scintigraphic images: I) The regional blood perfusion, the intensity of which is responsible for the elevation of scintimetric values short after trauma. 2) The increasing binding of labeled phosphonates to the newly built woven bone in the first two weeks after trauma. 3) The decreasing amount of woven bone in the callus after 2-4 weeks. 4) The inactivity of the extremities due to the plaster cast, which leads to a diffuse bone resorption, with increasing accumulation of the tracer after one week. 5) Duration and efficiency of inactivity, leading both to a more intense bone remodeling. Conclusion: The knowledge of the different physiological and pathophysiological factors leads the way to a correct interpretation of bone scintigramms, by that improving the diagnostic efficiency and reducing pitfalls in bone scanning after a trauma.

PO-2L1-11

PO-2L1-12

A. Vattimo, L. Burroni, P. Bertelli. Nuclear Medicine Unit, University of Siena, Italy.

M. Baehre, S. Pilgrim, K. Walter, E. Richter Clinic of Radiotherapy and Nuclear Medicine, Medical University of Luebeck, D-2400 Luebeck, Germany

WHOLE BODYRETENTION AND SPONGY-COMPACT BONE UPTAKE OF MDP-Tc99m: ITS RELATIONSHIP WITH SEX AND AGE. We used the 24-hr whole body retention (WBR) and spongy-compact bone uptake ratio (SCBUR) of MDP-Tc99m to detect the changes in bone metabolism occurring with advancing age. The study was carried out in 1664 asymptomatic patients aged 21-85 years (929 females and 735 males). WBR was expressed as % of the injected dose, whereas SCBUR was obtained by grading with a score from 0 to 2 the uptake between the proximal metaphysis (spongy bone) and the diaphysis of the femur (compact bone); in addition the score of the r a t i o between the uptake of the calvaria and cervical vertebrae was used. The WBR values were found to be higher in the younger groups (33,5 + / - 5,4 SD in females; 38.5 +/- 5.8 in males). The values decreased progressively up to the 31-35 group (32.8 + / - 6.8 and 36.3 +/- 3.6 respectivel y ) ; successively a slow increase was observed up to about the 51-55 year group in both sexes (42.2 + / - 6.2 and 42.5 + / - 5.5). This was followed by an accelerated rise in females. The difference was found higher within females than within males. A similar pattern was found as i t concerns score I , A score of 2 was found in 8% of the women more than 50 years of age and in 3% of the men. High uptake in the calvaria was found in 6.5% of women and in 0.5% of men older than 50 years. These data allow us to conclude that the changes in WBR and in SCBUR are related to the changes of bone metabolism.

580

RADIOIODINE THERAPY OF THYROID AUTONOMY: EFFICIENCY CONTROLLED BY QUANTIFIED SUPPRESSION SCINTIGRAPHY Purpose of the study: Quantified thyroid suppression scintigraphy is the method of choice to detect thyroid autonomy and estimate its functional relevance. Because there are only few investigations using this method to prove the efficiency of eliminating thyroid autonomy b~, radioiodine, we report own results. Patients and methods: This retrospective study includes 76 patients, treated with radioiodine because of relevant thyroid autonomy. All subjects had a complete investigation of thyroid function before and at the earliest 5 months after radioiodine therapy including quantified scintigraphy. Results and discussion: Autonomy could be completely eliminated in 69 patients (91%). This could be proved by quantified suppression scintigraphy in 47 individuals. In 9 individuals pertechnetate uptake before suppression (TcTU) was already within the-reference range for standard suppression regime (TcTUs < 1.6 %). In 13 of 15 cases without subsequent suppression because of cardiac risks, combination of pertechnetate uptake (TcTU) and TSH concentrations rendered remaining autonomy unlikely. Hypothyroidism was latent in 8 and overt in 2 subjects. In 7 subjects (9 %) autonomy was not eliminated completely: 1 patient developed hyperthyroidism after radioiodine, 4 exhibited an increased TcTU while TSH was suppressed endogeneously and in 2 subjects TcTUs was exceeded. Conclusions: Using the most sensitive method to detect thyroid autonomy in vivo,-the efficiency of radioiodine in eliminating thyroid autonomy could be proved. Nevertheless, quantified suppression scintlgraphy must be recommended to detect those subjects with remnants of autonomy, which may cause an increased risk of hyperthyoidism.

Monday, 2 September 1991

PO-2L1-13

PO-2L1-14

W. Bever, A. Lu, R. Montz Department of N u c l e a r M e d i c i n e University Hospital Eppendorf Hamburg, Germany

D CASARA,D RUBELLO,G SALADINI,A PIOTTO°,P BERNANTE °, A TONIATO°,b~ PELIZZO °. Radiotherapy and Nuclear Hedicine,°Surgical Department, University and General Hospital of Padua, Italy.

WITHDRAWAL AND RESUBSTITUTION OF L-T3 AND L-T4 IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA Endogenous TSH stimulates the 131-I-uptake of differentiated thyroid carcinomas(DTC). These patients are hypothyroid, and as TSH may stimulate proliferation of DTC (M~ller-G~rtner, 1990), the withdrawal and resubstitution of T3 and T4 was revised looking for a possible shortening of the hypothyroid period. Methods: Serum-TSH concentrations (sTSH) were determined by hypersensitive radioimmunoassay. Group 1 (n=14): sTSH was measured from the fourth week after L-T4 withdrawal (and end of T3 substitution) until 15 days later (131I-therapy). Group 2: measured from beginning of resubstitution with individual L-T4-dose and additional L-T3 ,in group 2A(n:8) T3 60 ug/d for 3 days, in group 2B(n=6) T3 60/40/20 ug/d for 5 days each. Resul%$: In group 1 sTSH reached it's maximum 15 days after withdrawal of L-T3 with 53,0 ± 30,3 mE/I(M ± SD). Day 10-12 showed sTSH values of 24,0 ± 16,1 mE/l(n=ll). 2 patients had extremely low values. Group 2A: after initial decrease in all patients 5 of them showed a new rise of sTSH on day 1 to 4 after stopping L-T3-application (6,1 ± 6,5 mE/l, n=8).Group 2B had significently lower values (2,4 ± 2,9 mE/l, n=6), also reaching sTSH <0,02 mE/l earlier (I0 ± 3 days) than group 2A (35 ± 22 days). Even after 15 days of additional L-T3 some increase of sTSH was found in three patients. Conclusion: the revised schema now is: Withdrawal of both L-T3 and L-T4 for Ii days, 131-I on day 12. During previous four weeks substitution with L-T3 20/40/60/60 ~g/d increasing weekly without L-T4. Beginning of resubstitution on the day after 131-I-application with individual L-T4 dose and L-T3 additional- 60/40/20/20 ~g/d, d e c r e a s i n g weekly. Afterwards L-T4 alone.

CLINICAL BOLE OF Tc99M MIBI SCINTIGRAPHY IN PARATHYROID IMAGING. A COMPARATIVE STUDY WITH TIiOI $CINTIGRAPHY, ECHOGRAPHY AND CT. Over the last i0 years,preoperative location of enlarged parathyroid glands received an important contribute from the use of the double tracer T]201-Tc99M scintigraphy (TTS).Recent]y,a new parathyroid agent, i.e. MIBI, has been proposed te be utilized for parathyroid imaging (Coakley et al,Nuc] Ned Commun 1989;i0:791). The present study was undertaken to evaluate the sensitivity,specif~ city,diagnostic accuracy, of MIBI scintigraphy (MS) in patients (pts) with hyperparathyroidism (HPT).Moreover, MS-data were compared to those ebtained with the other available conventional diagnostic techniques as TTS,neck echography (NE), CT and to surgical and histo]egic findings.At present, 15 pts were studied: 8 had primary (I ° ) HPT,7 secondary (II° ) HPT.Pts with I ° HPT: MS, NE and TTS resulted positive in 7/8 cases (89.5%),CT in 5/8 cases (62.5%).Evaluated together,MS and TTS showed a sensi tivity of 100%.Specificity was 91.6% for NE and CT,while it was 100% for MS and TTS.Diagnostic accuracy was 96.8% for MS and TTS, 90.6% for NE, 84.3% for CT. Pts with II ° HPT: MS showed 11/25 (44%) of the removed parathyroids in comparison to 48% with TTS,56% with CT and 72% with ME. Our data show that MS has high sensitivity,specific~ ty and diagnostic accuracy in pts with I ° HPT.Moreover, the combined use of MS and TTS migth give an important contribute to increase sensitivity in scintigraphic studies of abnormal parathyroids.

PO-2L1-15

PO-2L1-16

Ehrenheim Oh, Bunzend~hl H, Hundeshagen H. Abteflung Nuk]earmedizin und Klinik for Abdominal- und Transplantatlonschirurole,Medlzlnl~he Hochschule Hannover

A.Stavraka-Kakavaki ~, O.Fronistas*, G.Limouris*, H.Toumbouros ~, A.Giougi*, J.Papatheophanis**.

AS,SE&SMENT OF PANCREAS IRANSPLANT FUNOTION BY SIMULTANEOUS PANCREATIG-RENAL TRANSPLANT 801NTIORAPHY, The value of simultaneous pancreatic-renal trensplenL sclntigraphy In the essessment of pancreatic Lrensplsnt function was to be invesUgeted. PATIENTS AND METHODS. El patients received combined kidney and pancreas trensplent end were examined scinticjrsphicelly in the fellow-up. 6/8 had persisting good endocrine function, two suffered from lets par'iel thrombosis, one requiring insulin supplementetinn. 90 scintigrsphic examinations were performed after intravenous bolus injection of 370 MBq Tc-ggm-DTPA, on en everege I1 examinations per paLlent (range 5 - 24). The mean observation period was 175 days (range all 508). 5smiquentitetive visual essessment was made. RESULTS AND DISCUSSION. Initial nonvisualizetion corresponded to the clinical finding of initial nonfunction in the early postoperetive period in one case. The petlasL required Insulin supplementation during the rlrsL days. Likewise, In enother petienL pancreas visualizetion feinted eccording Lo rejection, which had been proceeded by kidney rejection some days ago. Although, organ visuelizetion disappeared in the following weeks completely in theL case, good endocrine funcLIon persisted. Sdntigraphic eveluation was easy Lo perform end corresponded to the clinical course within the early posLopereLive period (day ! - 50) However, any deterioration was unspecific. TheresfLer (day 50 - 300), organ visualizeUon feinLs. 5/0 transplants became invisible Inspire of retained endocrine function (inconsisLent visualization). One was invisible requiring insulin supplementation. Two remained visible, one with good endocrine Function inspire of partial thrombosis, and one requiring temporery insulin supplementaLIon. CONCLUSIONS. OTPA-scintigrephy is useful in the early posloperstive period. though any deterioration is unspecific. However, scintigraphy is not useful in the long-term follow-up, because of" the fainting end inconeistenL visuelizeLion.

*

Athens

University

-

Nuclear

Medicine

Department

-

Afore/on University Hospital - Athens - Greece. ** let Surgical Departm.-fzanio HospitaI-Piraeus-Greece EVALUATION OF THE VIABILITY AND FUNCTION OF PARATHYROID TISSUE TRANSPLANT IN PATIENTS SUBMITTED TO TOTAL PARATHYROIDECIOMY. The purpose of this study is the post-operative assessment of the transplanted parathyroid tissue in paLients Lhat have unergone total parathyroidectomy. The collimator Ls placed as near as possible to Lhe site of the transptant and the procedure starLs with the Dynamic acquisition, simultaneously with the administration of 2 mCi (74 MBq) of 2°III. The setLings are: Frame size 64, if required zoomed by 2, windows 20%. Time is I sec/frame for the first set of images and 5 sere/frame for the second set. Then, the Static acquisition follows by obtaining an image of 600.000 counts in 256 frame size zoomed by 2 and another one of ]00.000 counts with the addition of a lead shield over Lhe transplanL area. Then the Lhree sets of images are processed according to the protocol of our department. Candidates for total parathyroidectomy are patLenLs with primary or secondary hyperptasia of all the paraLhyroid glands. The patients are examined in the immediate post-operative period and after an intervaJ of 6-12 months. Eighteen patients were examined.From thes~ 12 (67%) had their transplant funetionning satisfaetority~ ] (16,5%) developed hyperplasia of the transplant with recurrence of the symptoms of hyperparathyroidism and

i n ] (16,5%) t h e t r a n s p l a n t was n o t f u n c t i o n i n g . C l i n i c a l and l a b o r a t o r y c o r r e l a t i o n was done f o r a l l t h e eases and t h e r e s u l t s proved t o be s a t i s f a c t o r y ,

581

Monday, 2 September 1991

PO-2Ll-17

PO-2L1-18

O.Geatti,F.Antonucci,G. Proto,E.Cattaruzzi, P.G. Orsolon,U.P.Guerra. Departments of Nuclear Medicine,Endocrinology and Nephrology 0.C.Udine(Italy).

A. Giordano, M.L. Calcagni, P. Oi Fazio, G. G a l l i . Universit~ Cattolica del Sacro Cuore. I s t i t u t o di Medicina Nucleate Largo Gemelli, 8. 00168 - ROMA

99 mTc-MIBI IN PARATHYROID SCINTIGRAPHY Thallium-Technetium subtraction scintigraphy presents some drawbacks (low count yield,poor Thallium uptake,movement of the patient,size and location of the adenoma),not completely solved. Coakley, in 1989 published his preliminary results indicating that 99mTc-MIBI can successfully localize parathyroid adenomas (I). We studied 41 people,comparing 99mTc-MIBI to 201T1 and ultrasound. Two of them were normal volunteers,one had a Plummer disease,one a multinodular goiter (with solid nodules by US),one a thyroid cystic lesion and thyrty-six were hyperparathyroid(19 primary and 17 secondary or tertiary).The majority of hyperparathyroid patients underwent CT as well. Among the patients with positive CT and MIBI scan, surgery (already done in 9 cases),always confirmed the presence of a parathyroid adenoma,ranging from 0.7 to 2.5 cm. False negative results were obtained in one patient,by Thallium (it was the smallest size adenoma) and in one by US (the lesion was deeply localized in the lower neck).In every case 99mTc-MIBI confirmed superior imaging ability than T1 and generally made useless any subtraction technique. In fact the diagnosis was eaaely done by only visual comparison of MIBI and Tc-partechnetate scans. In the non operated group all imaging modalities showed a significant agreement,but CT ar~ MIBI, always confirming each other, seem to provide the highest accuracy. 1-A.J.Coakley et AA."99mTe sestamibi - a new agent for parathyroid imaging". Nucl. Med. Comm. 10:791-794,1989

Recently contemporary dual-isotope acquisition has been proposed f o r TL/Tc parathyroid scintigraphy (PT) in o r der to improve diagnostic accuracy. Since 1987 we perform PT by standard sequential acquisition (SEq) f o l lowed by a contemporary dual-isotope acquisition (CONT) lasting 10 minutes. We intend here to compare the diagnostic r e s u l t s . SEQ=TL f i r s t (2mCi), Tc second (1.5-Z mCi) n o m a l i z a t i o n and subtraction. CONT=contemporary acquisition o f TL and Tc, normalization and subtraction. 50 consecutive subjects were submitted to the examination; they a l l underwent neck surgery. Using SEQ we obtained 97~ s e n s i t i v i t y , 50~ s p e c i f i c i t y and 86% accuracy. 5 patients had an inconclusive result due to head movement.Using CONT,performed in a subgroup of 30 subjects who volunteered to prolong the immobilization t i me, we obtained 88Z s e n s i t i v i t y , 67% s p e c i f i c i t y and 81~ accuracy. Concordance between SEq and CONT was obtained in 24/30 subjects. CONT allowed to make a correct diagnosis in 4/5 subjects who had an inconclusive SEQ result due to head movement. In conclusion: I)SEq demonstrated a s l i g h t l y higher diagnostic y i e l d than CONT; 2)CONT seems the procedure of choice in patients who cannot mantain a steady p o s i t i o n i n g ; 3)CONT may be routinely performed following SEq.

PO-2L1-19

PO-2L1-20

B.M.Grab, L.Duntas*, E.Henze, M.Clausen, W.E.Adam. Division of Nuclear Medicine and *Department of Internal Medicine I, University of Ulm, 7900 Ulm, Germany.

Kreisig T., C.R. Pickardt*, K. Horn*, G. Stalla*, F. Willemsen, C.M. Kirsch, P. K n e s e witsch. D e p a r t m e n t of R a d i o l o g y and of Internal M e d i c i n e Innenstadt*, U n i v e r s i t y of M u n i c h

*~NzTICS OF THYROTROPIN-RELKASING HORMONE DEGRADATION IN HYPERTHYROIDISM. The degradation of thyrotropin-releasing hormone (TRH) is influenced mainly by the thyroid hormones (L.Duntas et al.: Klin. Wochenschr. 68:1013-i019~1990). The aim of this study was to investigate the kinetics of degradation of exogenously administered TRH in euthyroidism and in different states of hyperthyroidism. METHODS: Ten euthyroid volunteers (EV) mean age 38 + 12y, (SD) and ten hyperthyroid patients (HT, aged 52 + 14y.) before and six weeks after antithyroid treatment because of M.Basedow (n=5),autonomous adenom (n=3) and diffuse autonomy (n=2) were included in this study. A standard dose of TRH (200pg i.v.) test was performed in each patient before and after six weeks of treatment. Blood samples for determination of TRH-immunoreactivity (TRH-IR) were collected at 0, 5 and 30 min after the injection of TRH. TRH-IR was estimated using a highly sensitive and specific RIA (Antibody K2B7, ED 1:120000, Sensitivity ipg=3 fmol/tuhe~ normal range in blood: 30-80 fmol/ml) and after extraction of blood samples in cold methanol (4:1 v/v). RESULTS: No statistic significance was observed between the basal TRH-IR in EV (TRH0: 35+9 fmol/ml, mean+SD) and in gT before (28ZII) or after treatment (34±T6) or between TRH 0 and T4,T 3 or TSH. The peak of TRH concentration (TRH~ax) was registered 5 min after TRH administration: 15317+4205 fmol/ml (EV) and 18274+ 6205 (HT). The quotients Q = TRHm,x/ TRH30min were 6.4for the EV, 5.2 for HT before and 6.2 after treatment. CONCLUSIONS: These results confirm the importance of thyroid function for the metabolism of TRH. The low Q-values in acute hyperthyroidism may indicate high enzymatic activity in hyperthyroidism and may serve as indicator of rapid TRH degradation in this disease.

PREDICTIVE VALUE OF TCTUs FOR THE OUTCOME OF IODINE CONTAMINATION IN EUTHYROID PATIENTS WITH THYROID AUTONOMY

582

201-Tl/99m-Tc (TL/Tc) PARATHYROIDSCINTIGRAPHY: SEQUENTIAL OR CONTEMPORARYDUAL-ISOTOPE ACQUISITION?

The TcTU after exogeneous TSH suppression (TcTUs) is the best a v a i l a b l e p a r a m e t e r to d o c u m e n t the q u a n t i t y of t h y r o i d a u t o n o m y in euthyroid patients. It was the aim of the study to e x a m i n e w h e t h e r TcTUs is a u s e f u l parameter to d e t e r m i n e the risk of h y p e r t h y r o i d i s m a f t e r iodine contamination. 17 p a t i e n t s (44 ± 7 years) w i t h c l i n i c a l and chemical (TSH > 0.3 uU/ml) e u t h y r o i d i s m rec e i v e d 500 ~ g i o d i n e / d a y for a p e r i o d b e t w e e n 3 and 14 m o n t h s after d e t e r m i n a t i o n of TcTUs. A p r e v i o u s iodine c o n t a m i n a t i o n had b e e n excluded. The s c i n t i s c a n s ~after TSH s u p p r e s s i o n r e v e a l e d focal t h y r o i d a u t o n o m y in 9 cases. I0 p a t i e n t s r e m a i n e d e u t h y r o i d w i t h n o r m a l TSH (group A). 7 p a t i e n t s d e v e l o p e d a b o r d e r l i n e h y p e r t h y r o i d i s m w i t h s u p p r e s s e d T S H b u t normal T3 and T4 and w i t h o u t any c l i n i c a l signs (group B). The TcTUs v a l u e s of g r o u p A w e r e found to 'range b e t w e e n 0.3 and 1.1% (median 0.8%), of g r o u p B b e t w e e n 1.0 and 4.1% (median 1.5%). 5 p a t i e n t s w i t h focal a u t o n o m y t o o k p a r t of g r o u p A and 4 of g r o u p B. Conclusion: In e u t h y r o i d p a t i e n t s w i t h v i s u a l ly s u s p e c t e d t h y r o i d a u t o n o m y no h y p e r t h y r o i dism after iodine contamination has to be e x p e c t e d if TcTUs is lower than 1.0%. This result is i n d e p e n d e n t of the e v i d e n c e of unifocal, m u l t i f o c a l or h o m o g e n e o u s d i s t r i b u t i o n of a u t o n o m o u s t h y r o i d tissue.

Monday, 2 September 1991

PO-2L1-21

PO-2L1-22

Graziana Lupattelli, Irene Virgolini, S.R.Li, H.Sinzinger. Dept. of Internal Medicine, University of P e r u g i a , Italy, a n d Dept. of N u c l e a r M e d i c i n e , U n i v e r s i t y of Vienna, A u s t r i a .

S. Maurea, J.C. Reynolds, A. Cuocolo, H.R. Keiser and R.D. Neumann. Nuclear Medicine Department and HypertensionEndocrine Branch, National Institutes of Health, U.S.A.

LOW DENSITY LIPOPROTEIN RECEPTORS: R E S U L T S O N "IN V I V O " S T U D Y

PRELIMINARY

Plasmatic l e v e l s of low d e n s i t y l i p o p r o t e i n s (LDL) a r e r e g u l a t e d by the r e c e p t o r p a t h w a y a n d m o s t L D L r e c e p t o r s a r e l o c a t e d in t h e liver. A r e c e p t o r d e f e c t d u e to g e n e t i c m u t a t i o n s of t h e L D L r e c e p t o r g e n e is b e l i e v e d to be t h e c a u s e of f a m i l i a l h y p e r c h o l e s t e r o l e m i a (F.H.), a d i s e a s e c h a r a c t e r i z e d by h i g h c h o l e s t e r o l l e v e l s and premature atherosclerosis. I n j e c t i o n of a u t o l o g o u s r a d i o l a b e l l e d 123I-LDL (i m g / m l ; 1 mCi) or IIIIn-LDL (i m g / m l ; 0.5 mCi), f o l l o w e d by h e p a t i c s c i n t i s c a n n i n g (sequential imaging and S.P.E.C.T.), was used to o b t a i n an "in v i v o " q u a n t i f i c a t i o n of h e p a t i c r e c e p t o r a c t i v i t y , b o t h in n o r m a l a n d h y p e r c h o l e s t e r o l e m i c p a t i e n t s . In p a t i e n t s a f f e c t e d by F.H. we o b s e r v e d no h e p a t i c increase of radioactivity with time confirming the liver L D L - r e c e p t o r defect. LDL-scintigraphy is a n o n - i n v a s i v e technique w h i c h c a n be u s e d to d i a g n o s e F.H. and to m o n i t o r t h e e f f i c i a c y of h y p o l i p i d e m i c t h e r a p y .

T h i s s t u d y w a s s u p p o r t e d by the O s t e r r e i c h i s c h e N a t i o n a l b a n k , J u b i l ~ u m s f o n d s P r o j e c t N o . 3778.

1311 MIBG UPTAKE A N D URINARY C A T E C H O L A M I N E LEVELS IN P A R A G A N G L I O M A S : COMPARISON OF BENIGN AND MALIGNANT TUMORS. We evaluated 1311 metaiodobenzylguanidine (MIBG) uptake and catecholamine (C) secretion in 28 patients (pts) (14 men and 14 w o m e n , age 3 7 4 - 1 0 (mean + S D ) ) w i t h benign (B) or malignant (M) paraganglioma (P). T w e n t y four hr urinary total C, vanillylmandelic acid ( V M A ) and metanephrine (MET) and pathologic confirmation of disease w e r e obtained in all pts. MIBG scan (0.5 mCi iv; images at 24, 4 8 and 72 hr) showed 1 or 2 lesions in pts w i t h BP and 1 to 28 abnormal foci in pts w i t h MP. Lesion uptake intensity on 48 hr images w a s measured w i t h a photographic densitometer (X-Rite Company, MI): optical lesion density (OD) and adjacent or contralateral normal tissue OD were used to calculate an intensity ratio (IR) for each abnormal focus. In pts with 2 or more lesions the average MIBG uptake w a s calculated. Results (median): (* p < 0 . 0 1 ) n MIBG IR* total C VMA MET BP 15 2.9 490 21 6.2 MP 13 5.5 514 19 7.2 (normal ranges: total C = < 1 1 5 , V M A = < 1 0 , M E T = < . 9 ) Since MIBG uptake reflects the concentration of neurosecretory granules in P, the difference in MIBG uptake between BP and MP may reflect a difference in stored C. Thus, while basal C secretion is similar in BP and MP, MP may be more prone to partial ischemic necrosis and catecholamine crises.

PO-2L1-23

PO-2L1-24

C.o Mazzi, C,a Mazzi.

J.Mihailovi~

Endocrinology Department St. Anthony Hospital Gallarate. Italy

Institute of Oncology,Medieal Faculty,University of Novi Sad,Sr.Kamenica 21204, Yugoslavia

STUDY OF ONE CASE WITH CONGENITAL ADRENAL HYPERPLASIA ORCHIDEDTOMIZED FOR BILATERAL TESTIS TUMOUR. A 2 6 - y e a r - o l d male has been studied fop the presence of normal testosterone, notwithstanding bilateral orchidec tomy top bilateral Leydig cell tumoun. Blood test (RIA) evidenced elevated ACTH, progesterone~ 17-alfa-hydroxyprogesterone, androstenedione, dehydmoepiandrosterone su iphate, supine plasma renin a c t i v i t y . PRL, TSH, T4~ crea tininaemia and e l e c t r o l y t e s were normal; LH and FSH were not suppressed; o e s t r a d i o l wasn't v e r y e l e v a t e d . I s o t o pic scanning with 1311-6beta-iodomethyl-nor-cholesterol revealed bilateral vivacious adrenal hyperplasia. We can suppose that the bilateral testicular tumour grew as a complication, even if uncommon, of congenital unknown a drenal hyperplasia. Reinke cmystalloids~ even if present in only 25-40 % of Leydig cell tumour, were not seen; ne v e r t h e l e s s the features were thought to be consistent with a Leydig cell tumour. ACTH dependence was demonstra ted with 1-17 ACTH s t i m u l a t i o n of 1 7 - a l f a - h y d r o x y p r o g e s =

METHODOLOGY AND CLINICAL VALUE OF RADIONUCLIDE ANGIOGRAPHY IN DIFFERENTATION OF "COLD" THYROID NODES

terone production and dexamethasone suppression of adre= hal androgen production. So, exists a therapeutic dilem: ma: can we get a Peal advantage out of dexamethasone tre a t m e n suppressing testosterone production ? This case highlights the need for both a functional and histological assesement of bilateral testis tumours befo re carrying out drastic treatments.

The goal of the study was to investigate if the perfusion parameters can be of value in differential diagnosis of "eold" thyroid nodes. This procedure was performed in 60 euthyroid^~atients with eold thyroid nodes.The first pass of ~mTe-pertechnetate through the thyroid nodes was investigated in this study.The quantitative parameters of perfusion through the "cold" thyroid nodes were obtained by our own computer program. Results: The ratio of perfusion between node and healthy thyroid lobe was significantly higher in carcinomas (0,8)than in benign lesions:eysts(0,1),autoimune thyreoiditis and benign solid nodes (0~4). The rate of radioactivity increasing in node was significantly higher in eareinomas(2,7)than in benign lesions(1,5).The ratio of radioactivity increasing rate between node and healthy thyroid lobe was also very significantly higher in careinomas(O,9)than in benign lesions(O,3).The efficiency of these parameters was also determined. Conclusions:The radionuelide angiography san be of value in differentation of "eold" thyroid nodes by some perfusion parameters.The ratio of perfusion between node and healthy thyroid lobe has a very high value in differentation of carcinomas and benign lesions,and systs and other solid nodes.The rate of radioactivity increasing and the ratio of radioactivity increasing rate between node and healthy thyroid lobe also may be used in differential diagnosis of ,,cold" thyroid nodes.

583

Monday, 2 September 1991

PO-2L1-26

PO-2L1-25 Kasatkin Y.N.,Mikerova T.M.,Silaev A.V. Nuclear Medicine Chair. Central Institute for Advanced Medical Studies. Moscow. USSR

THALLIUM-201 SINGLE-PHOTON TOMOGRAPHY IN PREOPERATIVE LOCALIZATION OF PARATHYROID ADENOMAS An effective means to preoperatively locate abnomal parathyroid tissue has remained a priority from time the first parathyroid exploration was undertaken. Many technique have been used to localize enlarged parathyroid glands:ultrasound (US),computed tomography (CT),radionuclide substraction scanning with thallium and technetium (TTS).But none of these modalities is ideal.During a 12-month period 27 patients were operated on for primary hyperparathyroidism. SPECT was performed in these patients after i.v. administration 2 mCi of TI-201.A rotating gamma-camera tomographic unit (GCA-90B,Toshiba) was used acquisition (180°rotation,32 projections for 30 sec. each, 2 hardware zoom, 128x128 matrix).Transaxial tomograms were reconstructed by filtered backprojection and reorganised into sagital and coronal sections.These sections were analysed visually the presence of thallium uptake. SPECT has advantages as compared with TTS: only one izotope is used, the length of investigation becomes shorter, scheme of processing more simple. This method includes more exact distingish between thyroid nodules and parathyroid adenomas, location of eetopic parathyroid tissue.Greater aceurancy is obtained when TI201 SPECT is used.

SCINTIGRAPHIC ANO ULTRASONOGRAPHIC ASSESSMENT OF HYPERPARATHYROiDISM(HYP}

SECONDARY

Both scintigraphy (SC) end schography (US) provide an accurate parathyroid localizationin primaryHYP, showing s safer surgical approach. In secondary HYP~ however, diagnostic role of those techniques seems less relevant since al} parathyroidglands (P) are necessarly explored by surgeon. This study sims at assessing reliability of SC and US in secondaryHYP. Out of 188 patients undergone to paratbyroidectomy for HYP, 64 patients executed both SC and US for P assessment. SC was carriedout according to the double tracerstechnique (TI-SOl and Tc-ggm pert.); US was performed by means of a 7,5 MHz probe. Removed P not previouslydetected by SC )averagediameter 10.5 mml had a diameter ( or = 6 me in ig~ of the case~, within ? and i0 mm in %~, within ii and 15 in 28~. Removed P not visualized by US iaverage diameter I0.2 ms} had a diameter < or : 6 ms in 15~ of the cases, within 7 and I0 mm in 55X, within II and 15 mm in 24X. The following table reports our findings in detectinghyperplastic P (diameter > 6 mm):

SC US SC+US Sensitivity 5~ 53~ 65~ Specificity g2~ 92~ 84~ Accuracy 65~ 65X 71~ Eterotopic P was localized in IIX of patients, while in 19X of the cases concomitantthyroid abnormalitieswere identified. Sensitivityof both SC and US was considerably low (due to small dimensions of hypsrpiastic P), but associationof both modalities allows a considerableimprovement. The very low false positive rate )high specificity) is an accuratm index sf P enlargement. But more important seems the identification of eterotopic P, since this abnormality affects a considerable percentage of our cases.

PO-2L1-28

PO-2L1-27 A V I L A , MIGUEL (3. Cons. Med. Nuclear, Libertad 666, 4200 Santiago del Estero, Axgentina E V A L U A T I O N OF PORTOSYSTEMIC S H U N T I N G T H R O U G H LOWER MESENTERIC VEIN IN LIVER DISEASES Equipment: gamma camera - data collector. Radiopharmaceuticah • I n - l l 3 m D.T.P.A. in 100 e l , pH5,5. Dosis: 407 MBq. Via: "per rect u m " through a catheter. Data collection: Since the first 10 minutes after the radipharmaceutical was given, up to 60 minutes. The detector was placed in liver and lung areas. Investigation time: Oct. 20/89 -Jan. 25/90. Patients for control and p r o b l e m s groups: 57 people (40 females, 17 males). Age: 46 to 78 years. All of t h e m underwent clinical investigation and lab tests. Equations used: a) shunt index=NO counts of lung/NO counts of lung--No counts of liver. b)slope correlation=(A1 • e -kmt) • (A2 • e -kst) where A 1 and A 2 intercept -- k~ and k2 are slopes of the exponential element (t 1 and t 2 are time). c) t student test, to prove significant difference between kl and k2. NO Shunt Correl/ t student (1 ¢0 ) Groups studied cases index slope G1 Control 10 0 1,112 No sig. dif. G2 Hepato-pancreatic 9 0 1,134 Sig. dif. t u m o r (I--II) G3 Hepato-pancreatic 11 43 -*4,29 3,99 Sig. dif. t u m o r (III--IV) G4 Benign Infest. 10 0 1,018 Sig. dif. pathology G5 Cirrhosis 19 72+-8,31 5,0 Sig. dif. Discussion and conclusion: The formulas were USed in all the patients and the shunt index was 0 in the control group, it was also 0 in the group 2 grades I and II (microscopic tumors), but a lack of correlation between kl and k 2 was observed. In the group of benign intestine pathology (polypus, etc.) the shunt index was 0 with a significant slope difference for time variation. The different stastitical tests resulting from mathematical analysis of magnitudes obtained from the biological m o v e m e n t of the studied system are a double set with a difference and a non-constant cyclic identity; the repeating time stops in the critical m o m e n t of our interest; they lead to the objetification of the efficacy of a disciplined evaluation of the suggested method.

584

Zsgni P., Bellanova B., Franchi R., gondi M., Marengo~., *SantoroA., Nonetti N. Servizis di Msdicina Nucleate, *Divisionedi Nefrologiae Oialisi Policlinicn S.Orsola-Malpighi,Bologna - Italy

J.Banzo, M.D.AbOs, E.Prats, M. Delgado, T.Escalera and M. Garc~a Miralles. Servicio de Medicina Nuclear. Hospital Cllnico Universitario. Zaragoza. Spain. "i.IEPATIC RADIONUCLIDE ANGIOGRAPHY IN THE DIAGNOSTIC OF THE ACUTE CHOLECYSTITIS"

The aim of this study was to establish the sensitivity and specificity of hepatic radionuclide angiography (HRA) in a large prospective serie of patients with suspected acute cholecystitis (AC). Methods: HRA and hepatobiliary scintiqraph~ (HS) were .performed .... w:ith a bolus injection "of Yym To-DIS I DA (185-222 MBq) in 167 patients. HRA results were considered positive for AC if there was a perichmlecystic hepatic irlcreased perfusion (PHIP) during the arterial phase. HS results were considered positive for AC if the gallblader was net seen within 4 hours, or a persistent nonVisualization of the gallblader at 30' postmorfine injection was noted (74 patients) or a "rim sign" was observed. All cases of AC were surgically and pathologically stablished. The diagnosis of "not AC" was considered by clinical, radioloqical and laboratory findings. Results: AC was co'nfir reed in 90 patients. Sensitivity and especificity of PHIP, nonvisualization of the gallblader and "rim sign" were 0.4~ and 0.9~, 0.94 and 0.,87, 0.$0 and 0.97~ respectivelly. In 11 of 9# patients with AC, gangrene (3), perforation (4) and empieme (4) was confirmed. In 8 of these 11 patients (72.7%) positive PHIP and/or a "rim sign" was seen. A correlation (p<0.001) between PHIP and "rim sign" was observed. Conclusions: i.- PHIP is an speciphic sign of AC. 2.- PHIP is more sensitive than "rim sign" and 5.- A positive PHIP associated with a "rim sign" may preclude the necessity of obtaining delayed images and the morfine administration.

Monday, 2 September 1991

PO-2L1-29 G,Barzen, W.Rlchter, De Brand-Passard, M. R.Felix

PO-2L1-30 P.Thies, 3. H i e r h o l z e r , A d l e r , H. E i c h s t ~ d t ,

Depsrtment of Radiology and Internal Universit~tsklinikum Rudolf Virchow, Free University of B e r l i n

A.

Medicine, Chbg

PORTALSYSTEMIC SHUNT FRACTION QUANTIFICATION USING TRANSRECTAL ADMINISTRATION OF IODINE-123 - HIDPM I N P A T I E N T S WITH LIVERDISEASE5

I n t h i s s t u d y , we i n v e s t i g a t e d t h e p o r t s l systemic shunt f r a c t i o n q u a n t i f i c a t i o n f o r o l i n l o a l u s e f u l l n e s and ~ p p l i o a b i l i t y . We examlned 41 p a t i e n t s w i t h d i f f e r e n t s t a g e s of l i v e r o i r r h o s i s (nutritional n=21, p o s t i n f e c t i o n a l n=2O). 2 6 p a t i e n t s had oesophageal bleeding, 2 suffered additional from hepatocelluiar carcinoma. 4 Patients were examined before and after livertransplantation. P o r t a l s y s t e m i c shunt q u a n t i f i c s t i o n was done by t r s n s r e o t a l a p p l i c a t i o n of 5 0 - 6 0 MBq i o d i n e 123 amphetamine which i s absorbed i n t h e rectum and t r a n p o r t e d v i ~ i n f e r i o r mesenteric vein to the liver =nd extr=oted. In case of port~lsystemic s h u n t i n g , i o d i n e 123 i s e x t r a c t e d i n t h e lung. By t h e r e g i o n o f i n t e r e s t t e c h n i q u e shuntindex ( l u n g ~ c t l v i t y / l u n g ~nd l i v e r ~ o t i v i t y ) qumntification is possible. Results: The shuntindex wms b e t w e e n 2 5 ~ mnd B 7 ~ i n p a t i e n t s with c i r r h o s i s stage A - C (healthy v o l u n t e e r s 0~ - 2 ~ ) . P a t i e n t s w i t h episodes of g a s t r o i n t e s t i n a l b l e e d i n g showed no d i f f e r e n t shuntlndex v a l u e s , compared w i t h those w i t h t h e same stmge and no episodes o f g a s t r o i n t e s t l n ~ l b l e e d i n g . P a t i e n t s w i t h extended a s c i t e s , low ~ibumin l e v e l s and low C h o l i n e s t e r m s l s l e v e l s had h i g h e r shuntindex v ~ l u e s {68~ - 87~) th~n p m t i e n t s w i t h o n l y s h l i g t l y diminished v a l u e s .

T.Szego, C . A . B u c h p i g u e l , V . R o p o l t o Nero, R.Abe,J. G a m a Rodrigues, H . W . P i n o t t i : - C e n t e r of N u c l e a r M e d i c i n e and D e p t o of G a s t r 6 e n t e r o l o g y of the Sac P a u ~ o U n i v e r s i t y M e d i c a l S c h o o [ - Brazil S C I N T I G R A P H I C E V A L U A T I O N OF THE G A L L B L A D D E R F U N C TION IN P A T I E N T S S U B M I T T E D TO V A G O T O M Y U S I N G 99mTc-DISIDA. The authors analyse the gallbladder (GB) emptying in 15 normal volunteers (NL) 15 pts submitted to proximal gastric vagotomy (PGV), i3 pts submitted to truncai vagotomy (TV), 14 to selective vagotomy (SV), both associated to hemigastrectcmy and gastroduodenostomy. Hepatobifiary imaging was obtained after intravenous injection of 185 MBq of 9.gmTedisida. 70' after the injection a standardized fatty meal was ac~ninistered. The area of resting GB as wei~ as the ejection fraction (EF) 30,45 and 60 minutes after meal were measured. Our results can be straarized as follows: the resting area of the GB was similar in a~L groups showing there was not dilatation of the GB. The GB emptying was similar in all groups until 30' after the fatty meal. There was a reduced emptying rate in TV and SV groups after 30'. PGV group showed similar GB emptying compared with the NL and both were different from the other two groups as they maintained the GB emptying after 30'. Conclusion: PGV do not interfere with the emptying of the GB after a fatty meat stimulus. In groups submitted to TV and SV associated to gastric ressection there was an interrzDtion in the GB emptying after 30' of the fatty stimulus. Facing these results a question raises whether the vagotomy, the gastric ressection or both are responsible for the ~GB motor alteration.

PO-2L1-31

PO-2L1-32

B.Caner M.T. Ercan, 6. Kapucu, G. Tatar, S. Nald6ken.. G. Erber~i, C.F.Bekdik. Dept. of Nuclear Medicine, Hacettepe University, 06100, Ankara, T~irkiye

.CA__STEL~NIM~R,AUDISIORAt CRIPPAF, MAFFIOI,IL, BURAGGIGL, Nuclear Medicine Division and *Surgical Onco]ogy "A" Division National Cancer Institute - Via Venezian,1 Milan

COLON SCINTIGRAPHY IN PATIENTS WITH IRRITABLE BOI~L SYNDROME USING 99mTc-LATEX PARTICLES

EARLY IIEPATOBILIARYEXAMINATION IN MAJOR HEPATIC RESECTION FOR CANCEROF q'Hl",LIVP,R ~-

Initial experience with 99mTc-latex particles (LP) to study colon transit was reported previously. Zn this study,we have investigated the use of 99mTc-LP in 20 pts with a clinical diagnosis of irritable bowel s~mdrome(IBS) in comparison to ii normal volunteers. Constipation was the predominant symptom in all the pts. After an overnight fast, the subjects were given orally 150 ml of water containir~. 37 MBq of 99f~TcLP.~,terier (A) and posterior(P) views of abdomen were obtained at 4, 5, 6, 7, 24 and 3i h. Percentage of radioactivity (RA) retained (% R) in the entire colon was calculated by the geometric mean of A ar~J P images after drawing_ ROI over the entire colon at each time interxml. % R (isd) is as follows: 6 h 24 h 31 h

In a previous report (*) we investigated the usefulness of hepatobiliary scan to confirme elinical or X Ray evidence of biliary fistula or collection in patients who underwent hepatic resection for eaneer (primary or metastatic) of the liver, In this prospective we subsequentially performed blindly (before X-Ray examination) the Br-IDA seen 8 10 days after major surgery to investigate : l I the status of biliary flow, 2] the presence of oeeult bile leakage or collection, {31 the correlation between scintigraphie findings and clinical (bioehemiea] liver funetion, bilirubin amount in the abdominal drainage of the right lobe) or radiologieal examinations (US or C'r}. I~'rom Oct '89 to Jan '91 we evaluated 41 pts who underwent major resectkm of the right lobe or resection of 3 or more liver segments. The mean amount of bi[irubin in abdominal catheter was 3 mg/lOOmh Liver function tests was normal in 32, abnormal in 9 pts. IDA seen was normal in 18 pts. In lg pts there was evidence of small bile leakage from the resection surface. In 3 cases there was evidence of dilatation of bile ducts with delay of intestine visualization. In one of these cases this finding worsened in a seeond ]DA examination and tile patient later underwent biliary percutaneous drainage. In g cases biliary leakage or eol]ection of a mild or high degree was observed: in 5 eases with visualization of abdominal eatheter; in 3 cases the collection was confirmed by C']' examination and eonsequently draiued by positioning a new bile catheter. In conclusion, 1DA scan confirmed the usefulness in monitoring patients after liver resection and helped in reducing the morbidity of major surgery.

IBS ....... 73.3 (22.6) 66.5 (23.70) 59.50 (38.0) Normal ...76.5 (18.6) 46.1 (27.13) 21.25 (9.7) p value , >0.05 >0.05 <0.05 Therefore, we concluded the.t: i-In patients, RA progress was slow, particularly in the ascer~ing colon compared to the normals. 2-A focal persistence of RA at ileocecal valve ~ra~ noticsd up to the termi1~ation of stz~dy in 30 % of the patients, but not in normals. Small bowel transit time was fot~d to be 233±72 min and 241+81 rain for normal and patient groups, respectively (p>O. 08). We t h i ~ that, 99~nTc-LP is a suitable agent to study the pathophysiology of colon in patients with IBS which warrants further studies.

(*) Castellani MR et el, t';ur O Nucl Med, vol 15, N 8, 532 (abstr), 1989

585

Monday, 2 September 1991

PO-2L1-33 C. Corbelli r P. Zagni. M; Dondi, C. Tosetti °, V. S t ~ e l l i n i ~ E. Rea o ; Nuclear Nedicine dept. o CI. Ned. i" Pol. S. Orsola-Malpig~hi Bologna Italy

PO-2L1-34 C. Corbelli, M. Dondi, M. Levorato, M. Campieri," P. Gionehetti~ G. Brunetti ; Nuclear Medicine dept. o CI. Ned. i Pol. S. Orsola-Malpighi Bologna Italy

GASTRIC EMPTYING EVALUATION FOR THE ASSESSMENT OF O P T I M A L C I S A P R I D E D O S A G E IN I D I O P A T H I C GASTROPARESIS TREATMENT.

C O L O N I C D I S T R I B U T I O N A N D R E T R O G R A D E S P R E A D OF A S A C O L F O A M A N D A S A C O L E N E M A IN U L C E R A T I V E COLITIS PATIENTS

C i s a p r i d e is a p r o k i n e t i c a g e n t w h o s e e f f i c a c y h a s b e e n d e m o s t r a t e d in c o n t r o l l e d c l i n i c a l trials. T h e a i m of t h i s s t u d y w a s to e v a l u a t e the correlation between blood cisapride c i r c u l a t i o n c o n c e n t r a t i o n and s c i n t i g r a p i c g a s t r i c e m p t y i n g (GE) in s e v e n t e e n p a t i e n t s (3M,14F; 20-62 yrs) w i t h o u t organic, s y s t e m i c a n d m e t a b o l i c c a u s e s of d e l a y e d GE. GE h a l f t i m e s (TI/2) w e r e h i g h e r t h a n 140 m i n u t e s (m+2SD of a c o n t r o l p o p u l a t i o n ) in all cases. A three-way-crossover double-dummy study with t h r e e 4 - d a y t r e a t m e n t phases, s e p a r a t e d b y at l e a s t 3 d r u g - f r e e days, w a s c a r r i e d out. P o s t p r a n d i a l GE of a s t a n d a r d t e s t m e a l l a b e l l e d in the s o l i d c o m p o n e n t (Tc99m cell c h i c k e n liver) w a s m e a s u r e d b y a g a m m a - c a m e r a (5 h o u r s a f t e r b r e a k f a s t ) in b a s e l l n e c o n d i t i o n s a n d in e a c h t r e a t m e n t period. D a t a w e r e f i t t e d by a p o w e r e x p o n e n t i a l f u n c t i o n and the r e s u l t s e x p r e s s e s as TI/2. B l o o d s a m p l e s w e r e d r a w n at b r e a k f a s t , l u n c h time and 1,2,3,4 and 5 hrs thereafter. Cisapride circulating c o n c e n t r a t i o n s w e r e m e a s u r e d by HPLC. C o m p a r e d to baseline condition [Tl/2=185+-10.6min.;m+-SEM), a significant i n c r e s e of GE was i n d u c e d by c i s a p r i d e 10mgx2 ( 1 2 4 . 2 + - 1 3 . 5 ; p = 0 . 0 0 2 , WRST) and 2 0 m g x l ( 1 5 0 . 4 + - 2 0 . 7 ; p = 0 . 0 5 ) , but not 10mgxl (180.5+-40.5). C o n c l u s i o n s . In the t r e a t m e n t of i d i o p a t h i c g a s t r o p a r e s i s : a ) c i s a p r i d e i0 m g b.i.d, is a s u b o p t i m a l dose; 2 ) b o t h 20 m g b r e a k f a s t and i0 m g b e f o r e m e a l s a c c e l e r a t e G E at l u n c h time; c ) t h e p r o k i n e t i c e f f e c t at l u n c h t i m e is m o r e c o n s i s t e n t w i t h i0 m g b e f o r e meals, d ) c h a n g e s in G E are s i g n i f i c a n t l y r e l a t e d to c o s a p r i d e p l a s m a levels.

R e c t a l a d m i n i s t r a t i o n is the b e s t w a y to a d e q u a t e l y t r e a t d i s t a l s i t e s of c o l o n i n f I a m m a t i o n . To i m p r o v e d r u g d i f f u s i o n and d i s p e r s i o n in the colon~ a n e w r e c t a l f o a m containing mesalazine with inert propellents (asacol foam) has b e e n d e v e l o p e d . The a i m of this s t u d y w a s to c o m p a r e the c o l o n i c d i s t r i b u t i o n and r e t r o g r a d e s p r e a d of b o t h A s a c o l f o a m 4 g and A s a c o l e n e m a 4 g/100ml, in i0 p a t i e n t s w i t h a c t i v e u l c e r a t i v e colitis. Each p a t i e n t w a s a d m i n i s t r a t e d the p r e p a r a t i o n s l a b e l e d w i t h I00 M b q T c 9 9 m coll 3 d a y s one f r o m t h e other, u s i n g c r o s s o v e r metod. A n t e r o - p o s t e r i o r s c a n s w e r e t a k e n at 5 , 3 0 , 6 0 , 1 2 0 , 1 8 0 a n d 240 min. In 4 p a t i e n t s scans w e r e a l s o t a k e n at 8 and 20 hrs. The b o w e l was d i v i d e d into 5 areas: rectum, sigmoid, d e s c e n d i n g , t r a s v e r s u m a n d ascending. Activity recorder over each segment was e x p r e s s e d as the p e r c e n t a g e o f ' w h o l e a b d o m e n radioactivity. Results: 6 patients showed the same s p r e a d w i t h b o t h p r e p a r a t i o n s ; a w i d e r foam spread was observed in three patients w h i l e e n e m a s p r e a d w a s i m p r o v e d o n l y in one. In one c a s e the foam d i d not r e a c h t h e s p l e n i c f l e x u r e , u n l i k e 3 of t h e e n e m a administrations. Maximum spread occured within 30 m i n in 9/10 p a t i e n t s w i t h f o a m and in 7/10 w i t h enema. C o m p a r e d to enema, foam s h o w e d a m o r e u n i f o r m a n d p e r s i s t e n t a d h e s i o n to the colonic mucosa and more favourable c h a r a c t e r i s t i c s for l o c a l i z e d t r e a t m e n t of u l c e r a t i v e colitis.

PO-2L1-35

PO-2L1-36

Mikael Ekraan, Martha Fj~tlling, Hans Person. Dept of Radiation Physics, Nuclear Med., Transplantation Surgery, Sahtgrenska Hosp. 413 45 GSteborg, Sweden.

E.Xynos.A:FouD_tos.E.Sbonias.A.M~ntides.J.SVassilakis ~qur~_~icalUnit and ~/clear Medicine Department of the Athens Navsl and Veterans Hospital. Greece

LIVER UPTAKE FUNCTION BY 1ODIDA CLEARANCE C A L C U L A T I O N IN LIVER TRANSPLANTED PATIENTS

I~Y~AROMYCIN ACCELERATES THE DELAYED GASTRIC ]B4PTYING IN PATIENTS WITH FUNCTIONAL DYSPEPSIA It has been recently shown that ei~rthromycin, acting as a motilin agonist, enhances the gastric emptying_ of solids in normals and patients with disbetic gastroparesis. In the present stud),, the effect of e1-ythromycin on gastric emptying of a standard radiolabelled solid meal in i0 r%ol~malst[bjects and on delayed gastric emptying of the same test meal in 8 p~tients with functional dyspepsia wss exomined. When placebo was administered patients with functional dyspepsia had a significsntly delsyed emptying of solids as compared to normels [a] duration of lag period (p<0.001]. b) overall tl/2 (V~0.00011 c) postleg tl/2 (p~0.05) and d) percentage of solid meal remaining in the stomach at 6 0 (p<0.0001) and 120 min (p<.0.001)]. 200 ~ of I V e
Choleseintigraphy with 99raTc-IODIDA is used to assess hepatecyte function and to visualize the hepato-biliary system (HBS).IODIDA, an iminodiacetic acid derivative is excreted mainly via the HBS, raaking cholescintigraphy possible even with very high bilirubineraia. By dynamic registration and by developing methods for IODIDA clearance rate(k) calculation, methods for quantitative assessment of uptake function of the liver are presented. Material and Methods: 28 cholesc, were performed on 18 liver transplanted patients. 200 MBq 99mTc IODIDA was given by bolus inj. and data aquisition was 10 see/frame during 30 rain, followed by static images. Two time - activity curves were generated; one from a Region Of Interest (ROI) over the blood pool and another from a ROI over the liver. Based on these curves two methods were developed for calculating clearance rate as percent of the blood pool cleared from radioactivity per minute (%/rain),kblood and as percent of the blood pool cleared by the liver per minute, kaiser. Results:Mean kblood for the patients without any complications was 15 %/min (sd=3).Two patients with rejection had BClr 6%/rain and repeated scans showed improvement during treatraent.Patients who presented with leakage had initially unaltered !Colood.The correlation coeff, between kli,~ - Icoloodwas 0.89 and the linear fit was kli~r=0.06+0.9 l*!co]ood respectively. Conclusion: By introducing a raethod for clearance rate calculation quantitative analysis of liver uptake function is possible. The linear fit between kliverand kblood shows that IODIDA is mainly excreted via the HBS.Therefore ~lood can be used to quantitate uptake function of the liver.

586

Monday, 2 September 1991

PO-2L1-37

PO-2L1-38

Frusciante V., Caruso N., Annese V., Modoni S., Barbano F., Perrone E., Petraeca Ciavarella G., Varraso A. Depts. of Nuclear Medicine and Gastroenterology Hospital C.S.S., S. Giovanni Rotondo (Fg), Italia

D.J. G ~ M B I N I , M . B O U C H A C H A , G.N. F R A N C O U A L , F. BRAGA, A. BERGER, M.A. C O L L I G N O N LE B O U E D E C , P. C U G N E N C , J.Ph. B A R B I E R , L. B A R R I T A U L T S e r v i c e de M i d e e i n e N u c l 4 a i r e , H 6 p i t a l L a @ n n e c , Paris . R A D I O E S O P H A G O G R A M OF G A S T R I C T R A N S P L A N T AFTER ESOPHAGECTOMY . The a i m of the s t u d y is to c o m p a r e e s o p h a g e a l g r a f t t r a n s i t a s s e s s e d by s c i n t i g r a p h y a n d m o t i l i t y a n d s e c r e t i o n of the g r a f t a f t e r e s o p h a g e c t o m y (AKIYAMA) . 16 p a t i e n t s a r e studied, 12 m a l e a n d 14 f e m a le, 55 to 81 y e a r s old, t h r e e m o n t h s to two y e a r s a f t e r the o p e r a t i o n p r o c e d u r e . S t u d y of the p r o g r e s s i o n of a b o l u s f o l l o w i n g a s i n g l e s w a l l o w of 30 M B q of 9 9 m T c - D T P A in 10ml of w a t e r is p e r f o r m e d . M o t i l i t y of the t r a n s p l a n t is s t u d i e d w i t h a standard three lumen system using a low comp l i a n c e p e r f u s e r . 24 h o u r s P h m e t r y is p e r f o r m e d w i t h an a m b u l a t o r y system. Total r a d i o n u c l i d e t h o r a c i c (I to 3.5s) t r a n sit times a n d t h o r a c o a b d o m i n a l (2 to 4.5s) are n o r m a l as c o m p a r e d to e s o p h a g e a l t r a n s i t times. In c o n t r a s t , an i n c r e a s e of the r a d i o n u c l i d e s e g m e n t a l t r a n s p l a n t e m p t y i n g time is f o u n d in all s u b j e c t s (4 to 19.5s) as c o m p a r e d to n o r m a l v a l u e s (<2.5s). G a s t r i c t y p e m o t i l i t y of the t r a n s p l a n t is f o u n d in 7 cases. The p e r c e n t a g e of time of Ph<4 is 54±8%, c o n f i r m i n g the p r e s e n c e of a residual g a s t r i c s e c r e t i o n t h r o u g h the c h i r u r g i cal v a g o t o m y . No s i g n i f i c a n t c o r r e l a t i o n is f o u n d b e t w e e n t r a n s i t a n d e m p t y i n g times, m o t i l i t y of Ph of the t r a n s p l a n t . The r a d i o n u c l i d e study shows the c l a i r a n c e a b n o r m a l i t i e s of the l o w e r t h i r d of the e s o phagoplasty

SCINTIGRAPHIC CLEARANCE ASSESSMENT CISAPRIDE TREATMENT

BEFORE

AND

AFTER

Aim of this study was to assess the effect of a recently developed prokinetic agent, Cisapride, on esophageal clearance in GER patients and to correlate motor findings with clinical performance of the drug. We have evaluated 10 controls and 30 GER patients (type I or II according to Savary-Miller classification) treated by cisapride. GER patients have been evaluated before the beginning of cisapride treatment and after 12 weeks of treatment (10 mg QID). After an overnight fast patients were administered 37 MBq of Tc99m sulphur colloid diluted in 15 ml of water; subjects were instructed to perform dry swallows at 15 sec intervals. 1 sec frames were acquired from 1 to 75 sec and 15 sec frames from 75 sec until the end of the test. Retention percentage (m±sd) at 15 sec was: controls 18.9±12; patients before treatment 42.1±22; patients after treatment 22.1±14.47. Data were compared by Student t test for unpaired data (controls vs.patients before treatment) and by Student t test for paired data (patients before vs. patients after treatment). A highly significant statistical difference was found between controls and GER patients before treatment (p<0.005) and also between patients treatment and patients after treatment (p<0.0005). In 24/30 pts. endoscopy detected no mucosal lesions after 12 weeks of treatment; in 3/6 pts. yet affected by lesions esophageal clearance was within normal range (mean+2sd of controls) while in other three pts. esophageal clearance was substantially unmodified.

PO-2L1-39

PO-2L1-40

G. Grimon, L.Andre, O.Bernard, F.Archambaud, B.HelaI,R. Lebtahi,B. Raffestin, A. Desgrez

M.S.Jovanovidl,B.Zmbova iThe B o r i s

Kidri~

Departments of Nuclear Medicine and Pediatric Hepat01ogy, H6pital de Bic@tre, 94275 BICETRE Cedex - FRANCE

Vin~ Faculty

DETECTION ANDQUANTIFICATION OF INTRAPULMONARY SHUNTS IN CHILDREN WITH CIRRHOSIS

BIOLOGICAL 99mTc

The s e a r c h for i n t r a p u l m o n a r y shunts (IPS) in c i r r h o s i s c h i l d r e n a w a i t i n g for liver t r a n s p l a n t a t i o n (LT) is s y s t e m a t i c : small IPS m a y ind i c a t e u r g e n t LT, w h i l e large IPS is u s u a l l y a contra-indication to LT. W e s t u d i e d scintig r a p h i c d e t e c t i o n of t h e s e small IPS. MATERIAL AND METHODS : 137 c h i l d r e n (age 6 ± 5years, 2 m o n t h s - 17 y) w i t h cirrhosis, w e r e d i v i d e d into 3 g r o u p s (gr) a c c o r d i n g to m e a s u r e m e n t of P a O 2 at rest u n d e r 21% (Pa21) a n d 100% (Pal00) 02 b r e a t h i n g : * g r I: 80 < Pa21 : n o r m a l * gr 2: 70
pts 91 9 37

CONCLUSIONS

I B/L 0.4 0.4 7.1

index ± 0.25 _+ 0.3 _+ 5.6

I pts w i t h B / L > 0 . 9 1 (1.4 %) 1 (ii %) 20 (54 %)

:

* B / L can d e t e c t IPS w i t h h i g h s p e c i f i c i t y , * the upper normal value of B / L is 0.9 (m+2SD), * scintigraphy c o u l d b e c o m e u s e f u l for t h e d e t e c t i o n a n d q u a n t i f i c a t i o n of IPS in t h e s e c h i l d r e n .

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"in vivo"

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decreases

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studied

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OF C A P T O P R I L

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587

Monday, 2 September 1991

PO-2L1-41

PO-2L1-42

Y . K u n i y a s u , S.Higashi, Y.Niio, J.Tomita, H . T a k i g a w a , and M . Y a m a n a k a . T e i k y o U n i v e r s i t y S c h o o l of M e d i c i n e , Tokyo.

N.S. Lin, C.J. Huang, Y.L. Wang, S,Q. Liao, S.J. Wang, R.S. Liu and S.H. Yeh. Department Nuclear Medicine,Taiehung Veterans General Hospital, Taiwan, ROC.

E V A L U A T I O N OF H E P A T O C E L L U L A R F U N C T I O N IN CHRONIC LIVER DISEASES WITH DECONVOLUT!ON ANALYSIS. -ANALYSIS USING THREE COMPARTMEMT MODEL-. A d i r e c t n o n i n v a s i v e t e c h n i q u e was dev e l o p e d to q u a n t i t a t e h e p a t o c e l ! u l a r f u n c t i o n w i t h c o m p u t e r a s s e s s m e n t of h e p a t o b i l i a r y s c i n t i g r a p h y o b t a i n e d a f t e r a d m i n i s t r a t i o n of t e c h n e t i u m - 9 9 m - P M T in 59 p a t i e n t s : 5 p a t i e n t s w i t h n o r m a l livers, 12 p a t i e n t s w i t h c h r o n i c i n a c t i v e hepatitis, 13 p a t i e n t s w i t h c h r o n i c a c t i v e hepatitis, 9 p a t i e n t s w i t h c o m p e n s a t e d liver cirrhosis, a n d 20 p a t i e n t s w i t h d e c o m pensated liver cirrhosis. Time activity curves of heart, w h o l e liver e x c l u d i n g b i l i a r y tract, b i l i a r y t r a c t and i n t e s t i n e w e r e g e n e r a t e d for 60 m i n u t e s a f t e r i n t r a v e n o u s i n j e c t i o n of 5 mCi (185 MBq) of T C - 9 9 m - P M T and w e r e s u b j e c t e d to d e c o n v o l u t i o n a n a l y s i s to d e t e r m i n e the m e a n t r a s i t time (MTT) in the l i v e r of the t r a c e r u s i n g m a t r i x algorithm. T h r e e c o m p a r t m e n t m o d e l w a s u s e d to a n a l y s e the c o r r e l a t i o n of k v a l u e s of the t r a n s i t i o n a l c o n s t a n t s b e t w e e n M T T s in c h r o n i c l i v e r diseases, and serial liver f u n c t i o n tests. D e c o n v o l u t i o n a n a l y s i s a n d three c o m p a r t m e n t a n a l y s i s can e l i m i n a t e the e f f e c t of t r a c e r r e c l r c u l a t i o n a n d d y s f u n c t i o n in b i l i a r y t r a c t a n d small intestine. Thus, p e r m i t t i n g d i r e c t m e a s u r e m e n t of h e p a t i c u p t a k e of t r a c e r a n d three c o m p a r t m e n t a n a l y s i s a p p e a r to p r o v i d e f u n c t i o n a l i n f o r m a t i o n u s e f u l in e v a l u a t i o n of p a t i e n t s with chronic liver diseases.

SEHIQUANTITATIVE TC-99M H~AO LEUKOCYTE IHAGING TO DIFFERENTIATE PERIAPPENDICEAL ABSCESS FROM ACUTE APPENDICITIS

Clinical management of periappendieeal abscess(ABS) and acute appendicitis(APP) is quite different. The latter need early appendectomy while the former requires conservative treatment followed by elective interval appendectomy. The purpose of the study was to differentiate ABS from APP by Tc-99m'H~AO leukocyte image(TC-WBC). Twenty-five patients(pts) were referred due to atypical symptoms and signs of APP(M:F=20:5, mean age=44 y/o). The leukocyte was labeled with the method of Ono st al,(J Nme] Med 1987;28:648). The mean labeling efficiency was 75-1-9% (56-88%). At 4 hours after injection, 800K counts static image over anterior abdomen was obtained. All patients were asked to void before imaging. Two ROIs were defined, one over the lumbar spine bone marrow(BM) and the other over the appendieeal zone(AZ). The mean pixel count of AZ/BM ratio(ABR) ~ s calculated. Six pts were diagnosed with gPP and 9 pts with ABS by exeisional biopsy. Ten pts with acute abdomen but with no appendicitis served as controls(CON). The mean ABR for CON, APP and ABS was 0.75034-0.0826, 0.84444-0.0930 and 1.14874-0.2142,respectively. The Rank test showed the ABR for ABS was significantly different from ~P and CON(P
PO-2L1-43

PO-2L1-44

Frusciante V., Annese V., Federici T., Caruso N., Modoni S., Barbano F.,Perrone E.,Valle G., Varraso A. Depts. of Nucl. Medicine and Gastroenterology, C.S.S. Hospital, San Giovanni Rotondo (Fg), Italy.

E.Oster-Jor~ensen. N.Qvist, S.A.Pedersen, C.P.Hovendal and L.Rasmussen. University Hospital, DK-5000 Odense C, Denmark.

Is'rm~m~w,M.. ESOPB[&GUS?

THE RELATION OF POSTPRANDIAL GALLBLADDER EMPTYING TO FASTED INTESTINAL MOTILITY IN HEALTHY YOUNG MEN.

DEFECT ] [ ] i & ~ l . . k ~ I . A L ' m ' [ ' T J W ( ] i ] ~ ' l " O ' n ~

Increasing evidence suggests that achalasia (A) is not restricted to the esophagus (Eckardt, 1989). We have investigated in I0 A pts. the gallbladder function by cholescintigraphy (CS) in the steady state and in response to CCK (i Ivy-dog Unit/kg in 5 min.) and the scintigraphic gastric (GS) emptying of a liquid caloric meal (Ensure plus 150 ml., 225 Kcal. instilled in the fundus via a naso gastric tube). Resnlts: No abnormalities were found during the filling phase of the gallbladder, but the ejection fraction was decreased (39.4±30.4 vs. 80.3±8.3)(M+SD) (p=0.007, Wilcoxon test) and the ejection phase was slower (9.1%[min±6.6 vs. 18.1±4.5, p=0.02) than in the controls. Three pts. showed normal values with CS. Eight pts. had an accelerated gastric emptying, with a steeper curve (Beta parameter 1.4±0.2 vs. 17±0.2, p=0,016) and a shorter TI/2 (41.5±15 min. vs. 74.7±11, p=0.007). None of t h e patients complained of g-i symptoms except for dysphagia. Upper g-itract endoscopy and liver ultrasonography were normal. Concl~io~m: In some pts. with A an extraesophageal involvement may be shown. This could be related to pathophysiological heterogeneity, different stages or different etiologies of the disease. The clinical significance of these findings is uncertain since none of the our pts. were symptomatic.

588

MATERIAL. Two groups of healthy young fasting males, six subjects in each group. METHOD. Bile kinetics was investigated by contineous infusion of 99m-Tc-HIDA and gamma camera recordings with analysis of areas of interest. From the time-activity curves it was registered when gallbladder emptying began following the ingestion of an omelette and a glass of water. Intestinal motility was recorded with a nasoduodenal six-channel tube by the continuous flow princip. The three phases of the migrating motor complex (MMC) were defined. In group A the meal was ingested in MMC-phase II. In group B the meal was ingested in MMC-phase III or immediately after. RESULTS. In groupA the gallbladder emptying began simultaneous with the ingestion in four and 4.5 to 13.5 min following the ingestion in two. In group B the emptying began 9 to 22.5 rain following the Ingestion. The difference was significant (p = 0.02). The emptying rate was calculated, hut no significant difference among the two groups was observed. CONCLUSION. The time for the commencement of gallbladder emptying following a meal relates to the phase of MMC: If ingested in phase II emptying begins almost immediately. If ingested in phase HI or phase I emptying begins after a lag period of 9 to 22.5 rain.

Monday, 2 September 1991

PO-2L1-46

PO-2L1-45 M. Pa~5~, *F. Nagy , J. L~ng, L. Csernay Albert Szent-GySrgyi Medical University Department of Nuclear Medicine, *Szeged Hospital, Szeged

Szeged, County

I~Popescu, G. Jovin, E. Timis, S. Giorgioni, N. Mocanu T. Safta-Fundeni Clinical Hospital, Bucharest, ROMANIA

HEPATO - PELVIC INDEX AS A FUNCTIONALITY TEST OF MONOCYTE PHAGOCYTIZING SYSTEM

THE V A L U E OF THE 99MTC-HMPAO-LABELED WHITE B L O O D CELL SCINTIGRAPHY (WBCS) IN INFLAMMATORY B O W E L DISEASE (IBD) WBCS was performed on 61 occasions in 43 patients with IBD. 18 patients had Crchn's disease, and 25 ulcerative colitis. Autolcgous leukocytes were labeled in vitro with 99mTcHMPAO. The mean lab~llng efficacy was 54.76 %. Images were taken 30 minutes, 2 and 4 hours after reinjection of the labeled cells. The leukocyte uptakes of six segments (jejunum, ileum ascending, transverse and descending colon, recto-sigmoideum) were assessed as negative, moderate, medium o r high. The whole activity determined by W B C S w a s compared with the Crohn's disease activity index (CDAI), and with the laboratory parameters of the inflammation. Colonoscopy- and biopsy w a s done and compared with the W B C S findings in 46 cases. A weak correlati6n w a s found between the WBCS activity and the laboratory results (for the fibrinogen and alpha2-globulin levels, r=0.35 and 8.39); no correlation w a s found with the CDAI. A comparison of the segment localization of the disease determined by WBCS and colonoscopy showed the sensitivity, specificity and accuracy to be 72.2%, 79.2% and 75.4%. Conclusion. WUBCS is a valuable method indicating the involved bowel segments in IBD. The W B C S activity of the bowel wall did not correlate with the CDAI, and weekly correlate with acute phase proteins.

Bone marrow scintigraphy of the pelvic zone was performed with 370 MBq colloidal 99Tc, where the time required ( s ) for hepatic scintigraphy and that for hone marrow of pelvic zone were noticed. The ratio of hepatic time / pelvic time was called " the hepatic pelvic index". The scintigraphies were performed in 28 neoplasic patients without liver methastasis or irradiations on pelvic zone, showed that this ratio was 0.030 +/- 0.001, varying between 0.02 - 0.05. This group represented "normal" values. Next, we performed seintigraphies of bone marrow of pelvic zone on 33 neoplasie patients, which were irradiated on pelvic zone or had medullar aplasia. These patients had a decrease ratio, due to the increase of the time required for bone marrow scintigraphy. Mean values of the index were 0.017 +/- 0.001 ranging between 0.007 0.038. Compared with "normal" values, the last index is statistically different. Oppositely, scintigraphies on 13 patients with hepatic cirrhoses showed an increase of the index due to the increase of the type of liver seintigraphy. Mean values were 0.079 +/- 0.009 ranging between 0.040 - 0.147, also statistically different compared with normal values, Our study showed that the hepatic - pelvic index indicate the ratio between liver monocitophagocitizing activity and that of bone marrow of pelvic zone. This ratio is constant in normal persons and provide informations concerning damage of these two organs, so this index is in objective and reproductive parameter.

PO-2L1-47

PO-2L1-48

N.Prandlni. L.Feggl, D,Cantarinl, G.Mandrloll, F.Maearlo, R.Reverberl

P.M.Cervl,

K. Seybold, A. Schmassmann, L.D. Frey, J.T. Locher, H.F. Fehr Departments of Nuclear Medicine and Gastroenterology, Kantonsspitul Aarau, Switzerland

St.Anna Hospital, Ferrara, Italy. RADIOLABELLED LEUkOCYTES AND SPECT IN INFLAMMATORY BOWEL DISEASE (IBD) Selntlgraphy with radlolabelled teukocytes is considered an indispensable teehnlque in the diagnosis and follow-up o f IBD. From Genuary 1990 to February 1991 we s t u d i e d 81 p a t i e n t s (13 M and 18 F, mean age 39.8) a f f e c t e d b y IBD. Eight p a t i e n t s had been g i v e n a hemieoleetomy and 2 a Intestlual by pass. The sclntigraphlc scans were performed with planar and SPECT technique. Twenty six patients were given an endoscopy (ES) with biopsy, 25 were given on X-ray and in 16 cases an uitrasonography (US) was performed. The presence and activity of the disease was confirmed in all the cases by clinical examinations and in one case by surgery. We found 22 cases of Crohn's Disease, 7 of ulcerative colitis (UC), one of non specific inflammatory disease and one negative case. Of the 211 segments studied 71 out of 80 resulted positive: the specificity of the scan for diseased segments was 100%, the sensitivity 88.7%. In 4 eases selntlgraphy identified th$ site of the disease only throught the use of the SPECT technique. ES 'had a s e n s i t i v i t y of 65.6% and it proved to be more accurate In p a r t i c u l a r in the t h a n s c i n t i g r a p h y In UC, examination of the rectum and sigmold colon. The s e n s i t i v i t y of t h e X-ray e x a m i n a t i o n was 53.4%, showing in o n l y one c a s e a diseased segment not previously identified as such by the selntigraphie scan. US proved to be the technique with the lowest sensitivity (43~). T o conclude selntigraphy may fall to diagnose the n a t u r e of the inflammation, but it is the most useful technique for identifying the sites affected and the degree of activity involved. SPECT is very useful, in the study of sites deep In the pelvis and of areas of low activity.

COLONSCINTIGRAPHY OF Tc-99m MAA/5-AMINOSALICYLIC ACID ENEMA INSTILLATED THROUGH A COLON TUBE INTO THE ILEOCECAL REGION IN SEVERE COLITIS Introduction: In severe colitis, effective 5-aminosalicylic acid (5ASA) therapy is severely compromised because of" severe diarrhea and low bioavailability of the drug in the colon mucosa. To overcome these pharmacological drawbacks a new therapy concept was investigated using a colon instillation tube. M e t h o d s : The tube (200era, 9-french) was coloscopically introduced into the ileocecal region in 6 patients with severe ulcerative colitis. 4 g 5-ASA enema (Salofalk®, 60ml.) was mixed with 185 MBq Tc-99m macro-aggregated albumin and instillated through the tube. Scintigraphy was performed at 0, 1, 4, 8 and 24 hours after instillation. Radioactivity was measured in the total colon and in 5 different anatomic regions by ROI-technique. The half-life was calculated according to linear regression. Results: Kinetic data showed no absorption of radioactivity and good correlation between colonoscopie and scintigraphic enema location. Despite a great individual variability 50% of the enema was calculated to be lost after 7 hours by bowel movements. The highest enema concentration (radioactivity / area) was found in the ascending colon for at least 8 hours, suggesting proximal colonic stasis. Radioactivity in the descending and sigmoid colon was clearly lower at all time points suggesting a more rapid transit through the left-sided colon into the rectum. The regional activity in percentage integrated over time was about 35% for ascending, 15% for the transverse, 15% for the descending, 15% for the sigmoid and 20% for the rectum. Conclusions: A therapeutical instillation of 5-ASA enema into the ileocecal region allows high 5-ASA concentrations in the total colon. Because of proximal colonic stasis the enema concentration is higher in the right-sided than in the left-sided colon. To maintain high 5ASA concentrations in the colon lumen, the dose interval should not exceed 12 hours.

589

Monday, 2 September 1991

PO-2L1-49

PO-2L1-50

P. Thouvenot, J-M. Antoine, M-H. Laurens, P. Maincent, A. Bertrand Nuclear Medicine Dpt., CHRU Nancy, 54511 Vandoeuvre, Prance.

Irene Virqolini*, Ch.M~ller**, P.Angelberger***, J.H6bart*, H.Bergmann*, J.Pidlich**, H,Sinzinger* *Dept. of Nuclear Medicine and **Gastroenterology, University of Vienna, and Chemical Institute, Research Center Seibersdorf, Austria.

DOUBLE LABELLING STUDY OF THE BIO-AVAILABILITY

~2RTIFICATION OF HEPATIC BINDING ~mTc-GAI~ACTOSYL-NEOGLYCOALBDMIN(NGA)

OF MINERAL WATERS. The aim was to study the in[re-corporeal fate of water as a function of their mineralty and of aeration. Twelve healthy volunteers drank 660 ml of water l a b e l l e d with Deuterium and with 1,85 MBq of m99Tc-Sulfur Colloids (with the p e r m i s s i o n of e t h i c s c o m m i t t e e ) . G a s t r i c emptying (GE) was monitored by stomach area scintigraphies every 10 mn over a period of 2 hours. Blood s a m p l e s were drawn e v e r y 15 mn and urines were collected after 60 and 120 a n . Plasma and urine d e u t e r i u m were d e t e r m i n e d by infra-red s p e c t r o m e t r y . Three water sorts were tested: A= l i g h t l y m i n e r a l i s e d and n o n - a e r a t e d water, B= l i g h t l y m i n e r a l i s e d and a e r a t e d water, C : s t r o n g l y m i n e r a l i z e d and a e r a t e d water. One hour after intake, the GE was 63 +- 5% for A, 72 +- 3% for B and 89 +2 % for C. However, the plasmic concentration of deuterium was the same for the three waters, The volumes of the A, B and C waters found in the urine according to urinary d e u t e r i u m c o n c e n t r a t i o n were respectively: 199 -+ 34, 212 + 40 and 146 -+ 29 ml, and were statitically different (p<0,01) between s t r o n g l y and w e a k l y m i n e r a l i s e d waters. The double labelling study allows us to conclude that: 1) the GE is faster for aerated waters and for h i g h l y m i n e r a l i z e d waters, 2) the w e a k l y m i n e r a l i s e d waters are r a p i d l y e l i m i n a t e d and participate, to a lesser extent than the strongly m i n e r a l i s e d waters, in the e x c h a n g e s with the interstitial compartment.

PROTEIN (HBP) V I A LIVER ECINTIGRAPHY

99mTc-NGAwas synthetised by covalent coupling of 2-imino -2 -methoxyet hyl- l-t hio-~-D -galact o-pyr anoside to the primary amino groups of human serum albumin and purified ~y ultrafiltration and size exclusion EPLC. Injection of ~mTc-NGA(150 MBq) at a rate of 3.5 mg (50 nmol; 1 ml) demonstrated the liy@r to be the exclusive site of uptake. Simulation of ~mTc-NGA-kinetics allowed quantification of HBp. We studied >250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and C stage cirrhosis had a lower HBP-concentration in the liver as compared to control individuals (0.85-1.2 umol/l). The group with the most advanced cirrhosis (Child C) had a significantly lower HBP-concentration (0.20-0,45 umol/ i) than Child A patients (0.60-0.85 umol/ i; p<0.01) and Child B patients (0.45-0.60 umol/l; p<0.05) . In patients with biopsy proven liver fibrosis (0.80-1.22 umol/l) no difference in receptor concentration to normal individuals was estimated. Patients with r e c e n ~ d i a g n o s e d acute viral hepatitis underwent repeated =="~c-NGAscanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged. The values obtained for HBP-concentration in the liver amounted to 0.30-0.50 umol/l liver for patients with hepatoma, to 0.40-0.60 umol/l in patients with liver metastasis and to 0.901.20 umol/l in cancer patients without liver malignancy. It is concluded that scintigraphic evaluation of functional hepatic cell mass using the new receptor-tracer ~mTc-NGA could provide an in vivo diagnostic mean allowing quantitative data on liver function beside assessment of liver morphology.

Abstracts PO-2L1-50A and PO2L1-50B see page 688

PO-2L1-51

PO-2L1-52

H. M a c a p i n l a c , C. Caluser, J. F i n l a y , C. L i n d s l e y , G. Krol, S. Yeh, S. L a r s o n and H.Abdel-Dayem. Memorial Sloan Kettering C a n c e r Center, N e w Yo~k, N Y USA

CASTI~I,[AN[MR*. ZAI4"ARONIG**, GASPARINIM*, DELL'AGNOLA**,SERI'IGNI g*, MARRAG***, MAH?IO1JI,*, BURAGGIGL*. *Nuel Ned. [)iv. NationalCancer Institute Milan, f* Pediatric Surg. Div. and *** IV Pediatric Div. of University of Milan - Italy. MAG3 SC1NTERAPHY IN INFANTS WITH CONGENITAL DIAGNOSIS 0f'

T I - 2 0 1 B R A I N S P E C T . C O R R E L A T I O N W I T H MRI I M A G I N G IN THE P O S T - T H E R A P Y E V A L U A T I O N OF PEDIATRIC PATIENTS WITH PRIMARY MALIGNANT B R A I N TUMORS. We e v a l u a t e d the a b i l i t y of T I - 2 0 1 b r a i n S P E C T in 8 p e d i a t r i c p a t i e n t s (6 children, 1 a d o l e s c e n t , a n d 1 y o u n g adult) a g e d 4-23 y e a r s to d e t e c t r e s i d u a l v i a b l e tumor, in c o m p a r i s o n w i t h M R I - G d - D T P A , following irradiation with conventional c h e m o t h e r a p y (2) or h i g h - d o s e c h e m o t h e r a p y with autologous marrow rescue(6). SPECT images were acquired after i n j e c t i o n of 2-3 m C i of T I - 2 0 1 a n d t u m o r to n o n / t u m o r r a t i o s w e r e o b t a i n e d i n attenuation corrected images whenever v i a b l e tumor was seen. C u r r e n t N R I - G d - D T P A s t u d i e s w e r e u s e d for c o m p a r i s o n . In 3 p a t i e n t s w i t h (+) S P E C T ( r a t i o s 15-17:1) c l i n i c a l f i n d i n g s and MRI w e r e s u g g e s t i v e of p r o g r e s s i v e d i s e a s e i n 2 a n d s t a b l e in i. In the 5 p a t i e n t s w i t h (-) SPECT, all had s t a b l e c l i n i c a l f i n d i n g s of 3-16 m o n t h s d u r a t i o n , but 4/5 s h o w e d a r e a s of G d - D T P A e n h a n c e m e n t of u n c l e a r significance. Our l i m i t e d s t u d y i n d i c a t e s a p o t e n t i a l l y i m p o r t a n t r o l e of T I - 2 0 1 b r a i n S P E C T in d i s t i n g u i s h i n g p o s t - t h e r a p y c h a n g e s from r e s i d u a l v i a b l e t u m o r in pediatric patients following aggressive t h e r a p y for m a l i g n a n t b r a i n tumors

590

IIYDR(INI
confirm file congenital (in ulero or neona{al) ulkrasonographie (US) diagnosis of monn (42 pts) or bilateral hydronephrosis 18 pts were 1 2 weeks old, 30 pts 3-4 weeks old, 10 pts 5 7 weeks old and 10 pts 8 10 weeks old In each patient relative renal uptake (RRU) at 2nd rain., level {high or low) of obstruction and response to diuretic Lest (DT) were evaluated 36/68 pts (5:3%)had bilateral hydronephrosis. In 32/68 pts (47%) an abnnnnal dilatation of ureter was observed: monolateral in 14 and bilateral IB in cases. In 2 cases there was no visualization of one kidney In 2,2 cases }{RUshowed a reduction of 5Z, in 4 cases of 6-10% and in 2 eases of 20%. The DT was performed in 56 pts. No response (t,1/2 > 15 min.) was observed in 26 of 87 kidneys evaluable. Scan changed the US diagnosis of monolateral pathology to bilateral pathology in 12 cases. A US bilateral disease resulted monolabral in 2 scans. The response to DT was not correlated with urn[oral dilatation or with a reduelion of RR/] lower than 10%. In children younger than 4 weeks the incidence of high degree malformations was higher than in those observed one month later. This observation was probably doe to a selection of patients related to the renaldisease severity. The major ukiliLy of renal scan in our investigation appears tile diagnosis of bilateral obstrud.ion in most eases associated with bilateral ureLeral dilatation. These malformations oriented elMeians [o pcrbrm further examinations (cloturing cystourethrography, iv urography) and eventually [o surgical correclion.

Monday, 2 September 1991

PO-2L1-53

PO-2L1-54

G.Ciofetta. F.Rognene. S.Ucce!le, G.Antognoni, R.Ronchetti. Pediatric Nuclear Medleine Lab.,IV Ped. C l i n , , Universltw "La Sapienza", Rome Ita!w.

J.J.Fettich R. Kenda, T. Kenig Departments of Nuclear Medicine and Pediatrics UnivePsity Medical Centre Ljubljana, Yugoslavia

PATTERNS OF REGIONAL LUNG PERFUSION DEFECTS: DIFFERENCES BETWEEN CHILDREN AND ADULTS. No report~ are available in t h e literature, concerning the identification of age-related patterns of regional lung disease: for this purpose we reviewed 180 lun~ scans performed Patients have been during t h e l a s t 2a m o n t h s . divided into two main groups: A=aged between ]/!Z a n d i0 w e a r s a n d H : a g e d o v e r i0 wears. Group A ~as further sub-divided into three s!/b-ZPOUpS (O-~. ~-6~ 7 - i 0 w e a r s ) . All the lung scans were reviewed bY an independent tbserveP, net aware of the erizinal scan ~epore s nor the p%tient~s dla~nosis. Perfusion abnorn!a] i t i e s w e r e d e s c r i b e d simp]w reeerrin~ to t h e i m s i t e a s ~Ipper m i d d l e and lower: linglllsr-se~ment and middle-loDe descriptions w e r e a]lolwed too. Localization frequencies were then measured, welding the ~o!!owlng ~esu]ts: l) m i d d l e parts of the ]un~s e~e vePw freque~t!~ compromised in both Srol]ps A snd B (55~ and ~8Z of patients). 2) Upper zones resulted worst in the group of child~.~,~ (A) as compared to adults (~0~ 3) Irregular ~at!ern against 18~ P<0.Ol). of defects bed tO be added to the other descriptions: this pattern was mostlw found in adult patients (aS~ against 16% of children, P
VALUE OF DIRECT CYCLIC RADIONUCLIDE VOIDING CYSTOURETEBOGRAPHY {RVCG} IN VESICOURETERIC REFLUX (VUR] DETECTINON IN CHILDREN R V C G is a well e s t a b l i s h e d m e t h o d to d e t e c t a n d f o l l o w up VUR in children. VUR is an i n t e r m i t t e n t f e n o m e n o n so d i f f e r e n c e s in p P e s e n c e a n d d e g r e e of reflux on Repeated VCG have been noted. The purpose of the study was to compare the Pesults of the second consecutive filling of the bladdeP with the Results of the first RVCG and in this way establish the value of "cyclic" RVCG. 48 patients, I - 5 yeaPs of age were investigated. RVCG was carried out using a small aspiration catheteP ( S . 3 / 2 . 4 mm). I m a g i n g w a s p e r f o r m e d c o n t i n u o u s l y during the first filling and voiding as well as duping consecutive fillings of the bladder, immediately after the first investigation at I fPame/ S secs. The eatheteP was not removed between the two investigations. VUR was detected in 19 pts (40%], bllatePal in S and unilateral in 14, that is in 24 kidneys alltogether. It was seen duping both, first and second investigation in Ii kidneys (I0 pts), duping the fiPst one only in 2, and only duping the second one in Ii kidneys (7 pts). The time fop the second filling did not diffeP significantly from the first one, but the amount of the saline used during the second study was significantly greater (p<0.0S). RVCG with several consecutive filligs of the bladder can therefore increase sensitivity of the procedure fop the d e t e c t i o n of VUR. W h e a t h e r it can also dec r e a s e the n u m b e r of f o l l o w up i n v e s t i g a t i o n s in clinical follow up of patients with VUR Remains to be established.

PO-2L1-55

PO-2L1-56

K.

~ahn,

D e p t . of Hospital

S.

B. Hesse, L. Brendstrup,

Fischer

Nuclear Medicine, University Mainz, D-6500 Mainz, Germany

SCINTIGRAPHIC ATLAS NORMAL VARIANTS

Of

BONE

MATURATION

S. Munck and the BUVI group.

Dept.s Clin. Physiol. & Nucl. Med. and Ped. Neonat., Rigshospitalet and Dept. Ped., Gentofte Hospital, Copenhagen, Denmark.

AND

In 1 9 8 9 t h e P a e d i a t r i c T a s k G r o u p of t h e EANM decided to publish an atlas, includ i n g a l l p a r t s of t h e n o r m a l g r o w i n g skeleton from birth to approximately 25 years, because at the present time, such a reference is c o m p l e t e l y missing in the literature. The aim of the project w a s to help physicans who are involved in Paediatric Nuclear Medicine to know how a normal, age related bone scan looks like. Since two years we collected in collaboration with Dr. Gordon, L o n d o n , Dr. G u i l e t t , Agen, Dr. Piepsz, Brussels a n d Dr. R o s a , Barcelona about 1300 bloodpool images, whole body scans and spot images of normal b o n e s c a n s o f a l l g r o u p s of a g e . The poster will display the first results and demonstrate some examples. The atlas will be published in 1992.

IS IT NECESSARY TO PERFORM RENAL SCINTIGRAPHY, ULTRASOUND AND VOIDING CYSTO-URETHROGRAPHY IN CHILDREN WITH URINARY TRACT INFECTION (UTI) ? In a still ongoing, prospective, multicenter study of children with newly diagnosed UTI the following 3 examinations were all performed, until now in 169 children < 7 y: Ultrasound (US) of the kidneys, ureters and bladder, DMSA renal scintigraphy, and voiding cystourethrography (VCU), either X-ray or isotope. Data are shown in the table. Examination results

n

VCU+ &/or DMSA+ &/or US+ 77 VUR > 2 24 VUR > 2, DMSA-, US12 DMSA+ 40 DMSA+, VCU-, US5 US+ 41 US+, VCU-, DMSA 21 +/-: abnormal/normal exam.; VUR > severe (>grade 2) V-U reflux.

(~)

(46) (14) (7) (24) (3) (24) (12) 2:

The study shows I) that a high proportion of children with UTI have anatomical or functional abnormalities, and 2) that ultrasound and VCU both yield independent information about such abnormalities (i. e. reflux, urostasis, focal scarring, reduced fractional share of one of the kidneys in total function etc.), presently considered to be of prognostic importance and hence also of importance for monitoring of infections and intensity of prophylactic medical treatment. Scintigraphy should only be performed if ultrasound and/or VCU is abnormal.

591

Monday, 2 September 1991

PO-2L1-57 J. Kotzerke. U. v. Smekal, H. Hundeshagen Abteilung Nuklearmedizin und spezielle Biophysik Medizinische Hochschule Hannover

~t_.~l~leev~1 P . M i n e h e f f ~nd :~.Vichev~ Institute of Nuclear Medicine,Hedic~*l AcAdemy PO-2L~sSStute of p u l m o n a r y Di . . . . . . P e d i a t r i c D e p ~ r t m e n t , ? 4 e d i c ~ i Ac~de~ay, S o f i a , B u l g a r i a . z~l~Ol~hl~IN ,~ ,*CTIVITY

ERRORS IN ERPF ESTIMATION WITH HIPPURANE USING A SINGLE SAMPLE METHOD IN CHILDREN Estimation of hippurane clearance as an equivalent ot effective renal plasma flow (ERPF) is one of the important quantification methods of nuclear medicine. An enormous number of techniques are known with specific advantages and disadvantages. The distribution volume method of Tauxe and co-workers is widely used but it is not well confirmed in the situation of the small distribution volumes Vd of children. For children Tauxe (1975) proposed the equation: ERPF = 3.87 I/C(t=53) + 19.3 with a standard error of SEE = 36.5 ml/min (I = injected Dose, C(53) = plasma concentration at 53 minutes after injection). This formula is based on a mean clearance of 313+186 ml/min and a Vd of 12.1_+7.6 I. This study investigated the feasibiity of the single sample method in smaller children (n=29) with BSA <1.1 m2 (mean: 1.09, range: 0.71-1.78). Clearance calculation was done from a 7 sample- (3 - 60 min) and two compartment analysis. There was no single time point useful for all Vd. In smaller children (n=18, Vd = 5.2~1.0, ERPF=278+65), the best correlation (r=0.90) and smallest error was found at 44 minutes (ERPF = 1.6 I/C(t=44) + 134.2,SEE = 28.9 ml/min). In older children (n=10, Vd = 9.4+2.4, ERPF=4O6-+119), lhe best correlation (r=0.96) and smallest error was found at 18 minutes (ERPF = 9.9 I/C(t=18) + 4.0,SEE = 28.9 ml/min). Using Tauxe's formula errors in ERPF estimation exceeded 50 percent. In children, formulas for single sample method are different from adults because linear regression fits best. Vd has to be taken into consideration because no single equation was valid for both, small and large Vd and ERPF values. Further it is possible that for normal kidney function another equation has to be used than for impaired renal function. When further dat~ (gamma camera or probes) are available they should be implemented to improve the validity of the clearance estimation. Tauxe WN, Hagge W, Stickler GB (1975): Estimation of effective renal plasma flow in children by use of single sample method after injection of orthoiodo-hippurate. In: Dynamic studies with radioisotopes in medicine, Vol I, Viena 1974, International Atomic Energy Agency, pp. 265-276.

PO-2L1-59 ~_tjavila_M., Lancha C., Dominguez L., Bas C. ,Avila C., Diez L. Department Nuclear Medicine. Hospital RarsSn y Cajal. Madrid. Spain. DIAC~OSIS AND FOLLOW-U~ OF NEUBOBLASTOMA (NBL) PATI~/~T BY 1-123-MIBG. We have examined 49 patients (21 M,28 F) whose ages are between 6 weeks and i0 years old. 28 patients were exami ned as a diagnosis and 21 patients left as a follow-up. A total of 135 examinations were made to carry out this diagnosis, stage of the extension and the follow-up,they were made: catecholamines and metaboiites determinations in urine of 24 hours, neuron-specific enolase determinations in blood, puncture-aspiration and/or puncture-biop sy of the bone marrow (BM) , several image techniques (IT) (thorax-X-rays ,ecography,CT,NMR) and isotopic studies with 99m-Tc-MDP and 1-123-MIBG. A sensibility of 91.6% and a specificity of 100% was obteined in the 28 patientsexamined with the purpose of localizing the primary tumour using a whole body scan with MIBG. In the 103 fo llow-up studies made, the IT detected the primary tumour in 35 cases against 47 with MIBG (p 0.01). IT detected 14 metastatic lesions against 38 with 5{IBG (p 0.01). In all the patients with spreading BM diagnosed by puncture biopsy, the MIBG studies showed this infiltration. The bone scintigraphy was useful for the primary tumour diag nosis and detection of the bone lesion, do not for the follow-up of this illness. The hole body scan with I-i23-MIBG allows an appropiate assessment of the patient with NBL. The morphological techniques are reserved for an initial assessment, pre vious to surgery and after the normalization of the scan,

592

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PO-2L1-60

~

C. PIRO', 3.A.MARTIN', R.GOSALBEZ*, A.GARCIA-BURILLO, UEL, S. AGUADE, F.PORTA, F.M. DOMENECH-TORNE. SERVICIO DE MEDICINA NUCLEAR. UROLOGIA PEDIATRICA'. HOSPITAL GENERAL "VALL D'HEBRON". BARCELONA - 08035. SPAIN. PRIMARY MEGAURETER : PROLONGED RENOGRAPHY WITH DOUBLE LASIX ADMINISTRATION AND EMPTY BLADDER. INTRODUCTION : ~"Te-DTPA scan is not usualty accepted as an accurate test to detect obstruction in primary megaureter (PMU). To differenciste ureteral dilatation from obstruction, renography (RNG) was modified by infusing lasix twice and by keeping the bladder empty. RNG results were compared with the follow-up medical and surgical diagnosis as well as with intravenous urogrsphy (IVU). MATERIALS AND METHODS : 34 ch dren were studied (5 females, 29 males, 15 days to 12 years old, average 1 year 10 months), including 48 excretory tracts (ET) with PMU : 13 bilateral, 5 rightsided and 17 lelt-sided. Of them, 19 childen (25 ET) were on medical follow-up, and 15 children (23 ET) were operated upon. Altogether, 45 RNG were performed : 45 minutes duration, previous oral hydratstion, double frusemide i.v. dose infused at 15 minutes (0 5 mg/kg) and at 30 minutes (1 mg/kg), empty bladder (either by catheter or by spontaneous m ctur t on st 30 minutes). The degree of kidney response (pelvis and calyces), and also of ursteral response was evaluated, as well as separated renal function. RESULTS : A summary of global results and results according to therapy is presented : INTRAVENOUS UROGRAPHY RENOGRAPHY II Obstr. No Obstruction & uptake,no o b s t r . No o b s t r u c t i o n

9 7 12

pro

i n o n i t o r i n ~ ~ of' t r e ~

i 0 21

DISCUSSION : Of 12 "obstructive" ET by UIV, 6 were definitely non obstructive by RNG and are under medical treatment only, and 6 were operated (3 because of contralateral obstruct ve PMU). One of the ET with normal renal function did not display a correct response to frusemide and is under medical follow-up. Of the 7 kidneys with decreased uptake and positive, not optimal response to frusemide, 4 were operated and 3 continue under medical treatment. COMMENTS : Prolonged RNG with double frusemide infusion and empty bladder seems an acceptable technique in the diagnosis and follow-up of children with PMU. Assessment of such RNG must take into account the residual renal function as well as diuretic response.

Monday, 2 September 1991

PO-2L1-61

PO-2L1-62

G . L a Cava, R . S c i a g r a , M . M a t e r a s s i * , R . I e n u s o * * U . M e l d o l e s i . N u c l e a r M e d i c i n e , *Dept. of Paed i a t r i c s , U n i v e r s i t y of F l o r e n c e ; * * D e p t of R a d i o l o g y , M e y e r H o s p i t a l ; F l o r e n c e , Italy.

A. Vattimo~ L. Burroni, P. B e r t e l l i , D. Meucci*, M. Messina* and G. Tots*. Nuclear Medicine Unit and Pediatric Surgery*, University of Siena, Italy. RADIONUCLIDE EVALUATION OF COLON TRANSIT TIME IN CONSTIPATED CHILDREN Constipation is a frequent and distressing complaint in childhood. It was, previously, assessed by X-ray films of the abdomen or of the stools after the ingestion of radio-opaque markers: b u t , this is a not reocomended method because of the patient radiation burden and stool collection. In this study we evaluated the segmental and total colon transit time in 10 constipated children (aged 4-13 yrs) using DTPA-In111 (2 MBq) given orally with the usual breakfast after an overnight fast. Anterior views of the abdomen were obtained at 6, 24, 30, 48, 54, 72, 120 and 144 hrs. The colon was divided into 3 main segments: Right Colon (RC), Left Colon (LC) and Rectosigmoid Colon (RS). Total (TC) and segmental percent retention were calculated at each time and the corresponding mean transit time (MTT) were obtained. The results were expressed as Mean (+/- $0).

S I N G L E K I D N E Y E F F E C T I V E R E N A L P L A S M A F L O W IN PAEDIATRIC PATIENTS WITH RENAL SCARRING A i m of this s t u d y was to e v a l u a t e w h e t h e r the m e a s u r e m e n t of s i n g l e k i d n e y e f f e c t i v e renal p l a s m a f l o w (skERPF) can b e u s e f u l for r e c o g n i z i n g the p r e s e n c e of r e n a l i n v o l v e m e n t (= renal s c a r r i n g ) in c h i l d r e n a f f e c t e d b y u r i n a r y t r a c t i n f e c t i o n (UTI). W e s t u d i e d 163 p a t i e n t s a f f e c t e d b y UTI (mean age 3.3 ± 3.5 years) for a t o t a l of 319 kidneys.' In c o r t i c a l s c i n t i g r a p h y w i t h D M S A 56 kidneys had clear renal scarring; i0 w e r e c l a s s i f i e d as u n c e r t a i n (class 0/i). R e n a l seq u e n t i a l s c i n t i g r a p h y w i t h 1 - 1 2 3 - O I H was p e r f o r m e d and the s k E R P F w a s c a l c u l a t e d u s i n g ext e r n a l m e a s u r e m e n t s a c c o r d i n g to our method. Results: class kidneys skERPF 0 253 333 i 49 0/i i0 295 ± 15 1 21 259 ± 46 2 13 237 ± 46 3 i0 187 ± 55 4 12 52 ± 27 The s k E R P F of s c a r r e d k i d n e y s ( c l a s s e s 1 4) was s i g n i f i c a n t l y d i f f e r e n t f r o m n o r m a l s (class 0); s k E R P F of all c l a s s e s w e r e s i g n i f i c a n t l y d i f f e r e n t f r o m e a c h other, e x c e p t c l a s s 1 f r o m c l a s s 2. A l s o the c l a s s 0/i k i d n e y s had a significantly lower skERPF than normals. In c o n c l u s i o n skERPF seems to r e c o g n i z e w i t h g o o d a c c u r a c y the d e g r e e of r e n a l inv o l v e m e n t in t e r m s of r e n a l s c a r r i n g a n d s e e m s well s u i t e d for f o l l o w u p and t h e r a p y e v a l u a tion in c h i l d r e n a f f e c t e d b y UTI.

RC MTT 52.8 (28.0)

LC 67.4 (37.4)

RS 92.9 (58.9)

TC 84.6 (41.6)

Our data show that the segmental and total MTT was high as compared with that obtained in normal subjects with X-rays method(19-33 hrs), suggesting the involvement of the whole colon in determining constipation. In addition the method resulted safe from radiation burden (2.4 mSv) and simple to perform.

PO-2L1-63

PO-2L1-64

B. HauDold-~euter. ~. Buc~inger r G.K. v. Schulthess. Klinik und Poliklinik fur N u k l e a r m e d i z i n , Dep. M e d i z i n i s c h e R a d i o l o g i e , U n i v e r s i t ~ t s s p i t a l ZUrich

F. JAMAR, N. LENERS, A. FERRANT. Centre de H~decine Nucl@aire, University of Louvain Medical School, UCL 54.30, av. Hippocrate 54, 1200 Brussels, Belgium

PITFALLS IN ~ONOCLONAL ANTIBODY IMAGING OF I N F L A M M A T O R Y PROCESSES I m m u n o s c i n t i g r a p h y of i n f l a m m a t o r y p r o c e s s e s with T c - 9 9 m - l a b e l e d mcnoclonal a n t i g r a n u l o c y t e antibodies (MoAb BW250/183) is a w e l l k n o w n method. The a n t i b o d y reacts with a n o n s p e c i f i c cross r e a c t i n g antigen (NCA 95) on the s u r f a c e of n e u t r o p h i l granulocytes. NCA 95 is an e p i t o p e of the c a r c i n o e m b r y o n i c a n t i g e n (CEA) w h i c h is p r e s e n t on the surface of some t u m o r cells as well as on neutrophil g r a n u l o c y t e s . In case of the p r e s e n c e of any C E A p r o d u c i n g tumor, a "false p o s i t i v e " r e s p o n s e m a y o c c u r w h e n s e a r c h i n g for i n f l a m m a t o r y p r o c e s s e s . W e p r e s e n t two p a t i e n t s with renal cell c a r c i n o m a and the s u s p i c i o n of an i n f l a m m a t o r y p r o c e s s . Case i: r e n a l cell c a r c i n o m a in 1985, 0 2 / 8 9 p a t h o l o g i c a l fracture of left h u m e r u s f o l l o w e d by osteosynthesis, 10/90 suspicion of s t a p h y l o c o c c u s o s t e o m y e l i t i s at this l o c a t i o n . MoAb-Imaging was p o s i t i v e . Sequential X-ray examination showed a progressive osteolysis consistent with metastatic destruction. H i s t o l o g y r e v e a l e d a m e t a s t a s i s of r e n a l c e l l carcinoma. C a s e 2: renal cell c a r c i n o m a in 1987, i1/90 p a i n and p r e s s u r e s e n s i t i v i t y in the right groin with a suspicion of soft t i s s u e i n f l a m m a t i o n or m e t a s t a s i s . N e i t h e r M R I n o r MoAb-lmaging could differentiate between infection and tumor. Aspiration revealed metastasis. Conclusion: In case of an u n d e r l y i n g m a l i g n a n t disease i m m u n o s c i n t i g r a p h y with MoAb is not r e l i a b l e in i d e n t i f y i n g inflammation. A s p i r a z i o n or h i s t o l o g i c a l p r o o f is necessary.

DETECTION OF INFLAMMATORY LESIONS NEUTROPENIC PATIENTS USING INDIU]4-111 HUMAN I ~ O G L O B U L I N S (HIG)

IN FEBRILE NON-SPECIFIC

The aim of the present study was to evaluate the use of glG-Inlll in febrile neutropenic patients (pts). 13 pts were studied, I0 of whom with absolute neutropenia (
593

Monday, 2 September 1991

PO-2L1-65

PO-2L1-66

M.L. Thakur, i C.S. Marcus z, p. Hennemann2, J. Butler 2, R. Sinow z, ~. Liu I, B. B~llou 3, B.A. Rhodes 4, T. Coons 4, J. DeFulvio , L. Diggles , and C. Minami 2. Thomas Jefferson Univ., pAI~ Harbor UCLA Med. Ctr., CA 2 , Pittsburgh Univ., PA 3, aNd RhoMed Inc., NM 4

V.Ankov,

Tc-99m LABELED MONOCLONAL ANTIBODY (MAb) IN PATIENTS WITH INFLAMMATORY DISEASES. MCA-480, IgM MAb that recognizes the 5,1xl05 lactoN-fueopeutaose antigenic determinants in each human ~utrophil (PMN) membrane and has a kd of 1.6xlO---M was selected from i0 MAbs evalued. After conjugation with 0.03 ug of c-DTPA, i00 ug of MCA480 was labeled with i0 mCi To-99m reduced with 5 ug Na2S204/ul reaction mixture. Molecular filtration and ITLC revealed >70% yield, <5% unbound Tc-99m and <3% colloid. Five adult patients presenting with RLQ pain consented to i.v. administration of the agent for diagnostic imaging and biodistribution sampling. The studies were positive in all patients within 3 hr post injection and pathologic correlation demonstrated early, moderate, and perforated appendicitis, early psoas abscess, and inflammation secondary to ascariasis. In 3 patients radioactivity distribut i o n at 3 hr was liver (58%), spleen (12%), bone marrow, (6%), blood (19%), lungs (3%), kidneys (3%), and bladder(l%). Activity boundbto PMN was 14.1% in a patient wit~ PMN count 3.2xi0 and 44.2% with PMN count 14.1xlO . In all patients radioactivity associated with lymphocytes was 9.1+1.3%, platelets 2.8+1.2% and RBC 1.6+0.6%. Encouraged by th-ese promising early results we have continued with further evaluation.

PO-2L1-67 M.A.Antar, R.T. Go, W.J. MacIntyre, Luders, P. Van Ness, G. Saha.

S.Stoimenova

Sofia,

Bulgaria

HM P A 0 - S P E C T IN ? A T I E N T 8 W I T H C L O S E D C E R E B R A L T R A U M A : AN A P P R O A C H IN D I F F E R E N T I A L DIAGNOSIS The differential diagnosis between brain concussion (BC) and cerebral contusion (CO) is a real challenge in Nuclear neurology. 23 patients (pts) with closed cerebral trauma (12 with BC and ii with CC) and 8 controls were studied with Gamma Diagnost C, Philips (64x64 matrix, 64x30 sec,LEHR 2D - FFT reconstruction). Two SPECT studies after i.v. injection of 500 MBq HM PAO (Amersham) were made. The labelling procedure and quality control followed ~ e c o m pany's instructions. The I SPECT was carried out on the 1-3 day post trauma and the II - between 15-20 day. The total mean brain uptake was 4,3% and the L/R ratios(rts) for different cortical areas were in the range of 1,02~ 0,05 in the control group. In 7/12 BC pts a single corti cal areas of hypoperfusion was found separately by 3blin dad observers on the I SPECT. The L/R rts calculated were 0,~Z0,Od. The same areas showed normal rts on the II SPECT. Two or more regions of hypoperfusion (L/R rts 0,71~0,04) werefound in all pts of the CC group on the I SPECT as well as on the II SPECT. Conclusion: The transient hypoperfusion in BC oppo site to intransient in CC may be used as one objective sign in their differential diagnosis. The degree of L/R rts diminition may be used as a second objective criterion.

PO-2L1-68 H.H.

Morris,

H.

The Cleveland Clinic Foundation, Cleveland, Ohio USA

LOCALIZATION C~ EPILEPTIC FOCI ~ F-18 FDG PE~ SCAN IN SURGICAL CANDIDATE PAT~/~TS WITH COMPLEX PARTIAL SEI~: CORRELATION ~ O1~ MODALITIES.

The aim of the investigation is to evaluate the relationship between F-18 FDG PET findings, MRI and prolonged EEG findings in patients who are surgical candidates for intractable partial complex seizures (PCS). We studied preoperatively 57 consecutive patients, 29 males and 28 females, their ages ranging from 5 months to 53 years. All patients underwent prolonged EEG/video recordings to localize the epileptogenic focus which was defined by epileptiform discharges and ictal onsets. In the interictal state, 2-10 mCi of F-18 F D G w a s given IV and scans were perfo rmed at 40 minute post injection using Posicam PET system. Reconstructed tomographic images in transverse, coronal, and sagittal views were analyzed visually and semiquantitatively. EEG showed positive lateralization in 41 patients (72%) and no lateralization or bilateral activity in 16 patients (28%). PET metabolic scans were positive showing focal hypometabolism in 47 patients (82%), negative in 4 patients (7%), and equivocal in 6 patients (10%). In contrast, MRI was abnormal in i0 (18%), normal in 41 (72%), and equivocal in 6 patients (10%). There was agreement between prolonged EEG/video and PET findings in 40 of 57 patients. In I0 out of 16 patients who showed no lateralization or bilateral activity on EEG, PET showed positive focal hypometabolism] F-18 FDG PET scanning is more sensitive than MRI and prolonged EEG/video monitoring in the evaluation of patients with intractable partial complex seizures.

594

K.Goranov,

C e n t r e of N u c l e a r M e d i c i n e , Military Medical Academy,

I.G. B 6 t t q e r , H . - P . S c h l a k e * , O. S c h o b e r , a n d W. B r a n d a u . Departments of N u c l e a r M e d i c i n e and *Neurology, University of M ~ n s t e r , G e r m a n y

CBF IMAGING WITH APALLIC SYNDROME DYSFUNCTION

T c - 9 9 m H M P A O IN B R A I N AND AGONAL CEREBRAL

DEATH,

This investigation was undertaken in o r d e r to study the diagnostic Usefulness of C B F i m a g i n g (CBFI) in t h e d e t e r m i n a t i o n of brain death. 18 p., , i0 f., 8 m., a g e d 17 - 70 y., 13 w i t h clinical brain death, 3 with clinical evidence of p e r s i s t e n t vegetative state but absent neocortical functions - "apallic syndrome" a n d 2 w i t h s e v e r e coma, s t a g e IV, w e r e s t u d i e d by neurologic examination, E E G as w e l l as b r a i n s t e m a u d i t o r y , BAEP, a n d s o m a t o s e n s o r y evoked potentials, SEP, b e s i d e s p l a n a r b r a i n s c i n t i graphy (perfusion sequence plus static images in f r o n t a l a n d l a t e r a l p r o j e c t i o n s ) w i t h 500 700 MBq Tc-99m-HMPAO with a radiochemical p u r i t y of > 90 % ' a n d n o r m a l b i o d i s t r i b u t i e n . W e f o u n d C B F I (no i n t r a c e r e b r a l tracer uptake) a g r e e i n g w i t h EEG, B A E P a n d S E P e n a b l i n g c o n f i r m a t i o n of b r a i n d e a t h in 12 o f 13 p a t i e n t s . In o n e case, h o w e v e r , in w h i c h c l i n i c a l e x a m i n ation and BAEP/SEP suggested brain death, EEG and CBFI revealed only slight alterations. Two apallic patients with gross EEG alterations showed only slight BAEP/SEP and CBF abnormalities. T h e t w o p a t i e n t s w i t h s e v e r e c o m a e x h i b i t e d no B A E P / S E P , m i n i m a l E E G a c t i v i t y , y e t n o r m a l CBF. In c o n c l u s i o n , C B F I is v e r y h e l p f u l in t h e difficult determination of brain death, especially if E E G a n d B A E P / S E P c a n n D t b e u s e d as in d r u g w i t h d r a w a l and hypothermia.

Monday, 2 September 1991

PO-2L1-70

PO-2L1-69 I.G.

B6ttger,

H.-P.

Schlake*,

O. Schober.

D e p a r t m e n t s of N u c l e a r M e d i c i n e U n i v e r s i t y of Munster, Germany.

and *Neurology,

E F F E C T OF A C E T A Z O L A M I D E UPON RCBF BY H M P A O AND S P E C T IN I N T E R I C T A L MIGRAINE. The aim of this i n v e s t i g a t i o n was to study the e f f e c t of acetazolamide, a c a r b o n i c a n h y d r a s e i n h i b i t o r used in the d e t e r m i n a t i o n of v a s o d i l a t o r y capacity, u p o n d e c r e a s e d rCBF in interictal migraine. 16 a s y m p t o m a t i c p., 4 m., 12 f., aged 18 - 58 y., w i t h m i g r a i n e with, n = ii, and w i t h o u t aura, n = 5, w i t h hemiplegic, n = 8, or opht h a l m i c symptoms, n = 3, were s t u d i e d w i t h o u t as well as 15 min. a f t e r i.v. a d m i n i s t r a t i o n of 500 mg a c e t a z o l a m i d e (Diamox R) by T c - 9 9 m HMPAO, 500 - 700 MBq, and SPECT. I n t e r p r e t a t i o n of t o m o g r a m s was p e r f o r m e d s e m i q u a n t i t a t i v e l y (color scale) and in part also s e m i q u a n t i t a t i v e l y (focus v e r s u s c o n t r a l a t e r a l ROI). Of the 16 p. w i t h b a s a l l y d e c r e a s e d rCBF 13 d e m o n s t r a t e d n o r m a l i s e d rCBF in the r e s p e c t i v e r e g i o n under acetazolamide, 1 p. w i t h h e m i p l e gic m i g r a i n e r e v e a l e d an improvement, and 2 e l d e r p. w i t h m i g r a i n e w i t h o u t aura and with m a r k e d l y d e c r e a s e d basal rCBF did not show any change. U n d e r a c e t a z o l a m i d e no i n c r e a s e of rCBF a s y m m e t r i e s was observed. In conclusion, our s t u d y d e m o n s t r a t e s - in c o n t r a s t to p. w i t h T I A - intact v a s c u l a r r e a c t i v i t y ( v a s o d i l a t o r y capacity) to a c e t a z o l a m i d e in the m a j o r i t y of m i g r a i n e p a t i e n t s with i n t e r i c t a l l y p e r s i s t e n t rCBF d e c r e m e n t s and might, therefore, aid in the d i f f e r e n t i a l d i a g n o s i s b e t w e e n m i g r a i n e with aura and TIA.

B.,Deisenhammer

E.

Wagner-Jauregg-Krankenhaus W a g n e r - J a u r e g g - W e g 15 A-4o2o Linz, Austria BRAIN SPECT IN MIGRAINE, INTERICTAL AND ICTAL INVESTIGATIONS SPECTstudies with I{~DAOand I ~ permit an approximate evaluation of regional cerebral blood flow (rCBF) and - as long as rCBF is linked to cerebral metabolism - also of regional metabolism. Performing SPECT in migraine patients with and without aura we found characteristic patterns of tracer distribution" 1.Multiple small areas with increased tracer uptake (patehy-pattern) 2.Large area of increased uptake (hot focus) 3.Decreased tracer uptake in the tenporo-occipital codex, mostly SynT~tricaI (posterior decrease) 4.Large areas with severely decreased tracer uptake (defects) 5.Slight side differences of larger cortical segnents (side difference) These results were obtained in 16 patients with/and 26 without aura; we found patchy-pattern in 16/2o cases, hot focus in 2/6 cases, posterior decrease in 12/22 cases, defecLs in 6/o cases, side difference in 2/4 cases. Several patterns, including defects, were seen during attacks with aura, mere or less disappearing in the interictal state. Discussion: Though individual patterns being non specific and their interpretation scmetimes being speculative, the ccn~oination of uptake patterns are typical in migraine patients. Patchy-pattern may be indicative of smaU circumscribed metabolic disturbances. Posterior decrease may reflect the vulnerability of this region in migraine. Defects, especially i f disappearing after the attack, is prcbably the expression of circunscribed perfusion-disturbanee. Hot focus may be only a variant of patchy-pattern. The c(rnbination of patchy-pat~rn and posterior decrease seemto be pathogncmenic for migraine.

PO-2L1-72

PO-2L1-71 E.E. Camarqo, H. Rivera-Luna, S. Sostre, Saric, G.D. Pearlson, D.R. Mclec~, Z. Madary, G. Harris and H.N. Wagner, Jr. Hopkins Medical Institutions, Baltimore MD,

Brucker

R. Hoehnszabo, J. ~he Johns USA.

C~gE~gAL ACTIVATIf~N DURING THE STROOP TEST ID~gTIFIED BY ~ SPECf IMAGING. The purpose of our study was to determine whether SPECT imaging with [99m]Tc-}~4P~/9 was sensitive enough to identify the cerebral activation dzar~es created by the Stroop attentional-conflict paradigm. Five healthy, right handed, normal volunteers (22-42 yrs) were studied before and during the performance of the Stroop test. A high resolution (FWI~4: 4.7~m in air; 5-8nm in water), four detector, dedicated cerebral imaging system and 740 MBq of the tracer were used. For the baseline study, the subjects were injected while watching a series of color boxes on a video monitor. For the activation study, the subjects were injected at two n~inutes into the performance of the Stroop test. ~ne activity of 44 cortical and subcortical regions in each subject were expressed as ratio to the cerebellum. Regional changes were analyzed using MANOVA for repeat measthremen~ and were considered significant if p<0.05. Two-way subtraction images were also obtained. Significant changes (increases of 5 - 9.5%) were found in the high anterior cingulate gyrus, left putamen, left precentr~l, and left motor cortices. These regions may be involved in the processing of color naming versus reading. We also found changes in the left caudate, left thalamus, and high right temporal region. We conclude that SPECT can identify cerebral perfusion changes caused by activation studies such as the Stroop test and may be used to identify brain centers involved in the performance of other cognitive tasks.

H Caner, B. Caner, G. Erbengi, O. Ozcan, T. Ozgen, C.F. Bekdik. Depts of N e u r o s u r g e r y and N u c l e a r Medicine, H a c e t t e p e University, 06100 Ankara, T ~ r k i y e CEREBRAL BLOOD FLOW VENOUS M A L F O R M A T I O N S SP~-CT

E V A L U A T I O N OF ART£RIO(AVM) W I T H T c - 9 9 m - H M P A O

Nine p a t i e n t s w i t h C T and a n g i o g r a p h i c a l l y proved intracranial AVMs were evaluated w i t h 9gmTc-HMPAO SPECT to determine cerebral blood flow(CBF). None of the patients had significant a n g i o g r a p h i c steal. Five p a t i e n t s out of 9 und e r w e n t b o t h pre- and p o s t - o p e r a t i v e (48 h following total e x c i s i o n of AVM) gg~Tc-HMPAO SPECT study, while 4 had only p r e o p e r a t i v e study. On pre-operative images, the areas corresponding A V M were all detected as localized defects, lpsilateral and contralateral regions of h y p o p e r f u s i o n were d e t e c t e d in 6 and I patient respectively. These areas of h y p o p e r f u sion were thought to be due to steal p h e n o m e n o n of AVM, since no corresponding a b n o r m a l i t y was detected o n C T images. Interestingly, angiograhic findings of these p a t i e n t s were not sugg e s t i v e of steal phenomenon, P o s t - o p e r a t i v e regional hyperemia indicating normal p e r f u s i o n p r e s s u r e b r e a k t h r o u g h was detected i n 3 p a t i e n t s out of 5 who underwent preand post-operative SPECT evaluation. Ipsilateral and contralateral areas of hyp o p e r f u s i o n s e c o n d a r y to steal p h e n o m e n o n detected p r e o p e r a t i v e l y d i s a p p e a r e d on postoperative images. Thus, CBF studies using 9~Tc-~n~PAO S P E C T ar~ useful in the e v a l u a t i o n of pre- and postoperative h e m o d y n a m i c cba_nges of A V M and it was superior to a n g i o g r a p h y in revealing steal phe~

595

Monday, 2 September 1991

PO-2L1-73 G.Cantinho,

PO-2L1-74 J,M.Perro,

A.Levy,

Inst. Medicins Nuclear, FML Dept. Neurology, NSM, Lisbon,

F.Godinha

Catafau A., Nicolas J.=, Lome~a F., R. ~, Garcia J.R. and Setoain J.

Estruch

Portugal

APHASIA ANO NEGLECT AFTER SUBCORTICAL CORRELATION WITH SPECT HMPAD

STROKE, BEHAVIORAL

In 17 cases of subcorticsl lesions [6 hemerrhages, ll Infarcts) localized by CT or MRI,standardized neuropsycho~ logical examination and 9Bm-Tc HMPAO Spect was performed in order to study the role of cortical diaschisis in sub cortical aphasia snd neglect. In the HMPAO Spect study s semiquantitative assessment of regional cerebral blood Plow wss performed by means of s relative perfusion index between the two hemispheres. Squared regions of interest 4x4 pixel were placed in the anterior, medial and posterior cortical sreas of the brain in four consecutive transaxial slices, excluding cersbellum. Three index values for each of the four slices were calculated by the ratio between symmetrical count vsluas. Among 6 left brain damaged patients all four aphesics had lePt certlcsl hypoperfusion,and none of the non aphesics showed reduced cortical perfusion. On the ll right hemispheric damaged subjects two had neglect,but only one of these had a regional parietal hyp~ perPusion. Moreover two patients with localizeQ C@rontal) hypoperfusion Palled to show neglect. While there seems to be a relationship between le~t cortical hypoperfusion and subcortical aphasia,the link between right subcortical leslons,cortlcal diaschisis end neglect is less clear.

PO-2L1-75 Muxi A. and Setoain J. Nuclear Medicine, Neurology ~ and Infectious Diseases ~ Dpts. Hospital Clinic. Barcelona. SPAIN. BRAIN 99mTc-HMPAO S P E C T IN H U M A N POSITIVE INDIVIDUALS (HIV+).

Nuclear Medicine and Internal Medicine ~ Departments. Hospital Clinic. Barcelona. SPAIN. REGIONAL CEREBRAL BLOOD A L C O H O L I C S BY 9 9 m T c - H M P A O

FLOW SPECT.

EVALUATION

IN

CHRONIC

In order to assess the regional cerebral blood flow (rCBF) patterns in patients with chronic alcoholism we have evaluated 99mTc-HMPAO brain SPECTs performed to 38 asymptomatic alcoholic men (mean age 45 years) entering an outpatient treatment program. All patients had abstained from ethanol the two weeks prior to the examination and none had neither withdrawal symptoms nor cognitive disfunctions. Twenty control volunteers with ethanol consumption of less than 20g a day were also examined. The study protocol was approved by our Ethical Cormmittee. SPECT was carried out with a Elscint SP4 camera.For reconstruction, a Butterworth (0.5,6) filter was used, obtaining 2 pixel thick slices (4.5mm/px) in a 64x64 matrix. Statistical analysis was performed using the Student's t-Test. Twenty five alcoholics (65,8%) and two controls (10%) had abnormal SPECT (p<0.001). All brain lobes were affected in the following proportions: frontal (55%), temporal (35%), parietal (20%) and occipital (20%). Furthermore, a highly significative inverse correlation between rCBF and the amount of alcohol intake in the previous month was observed (p<0.001). We conclude that asymptomatic chronic alcoholics show frequently an impaired rCBF pattern by HMPAO SPECT, The affecting mainly frontal and temporal lobes. relationship between this impairment and the recently ethanol intake suggests an acute or subacute effect of ethanol on cerebral microcirculation.

PO-2L1-76

Catafau A.,LomefiaF.,Herranz R.,Abos J.~,Miro J . ~

I~GNODEFICIENCY

VIRUS

Brain HMPAO-SPECT was performed to 26 HIV+ (23 male, 3 female, age range 20 to 55 years), in order to assess regional cerebral blood flow (rCBF) in these patients. Patients were divided in 3 groups: A) 8 HIV+ without neuropsyehometrieal impairment (NPSI); B) 8 HIV+ with NPSI (5 Encephalopaty-Demetia Complex and 3 with only 1 abnormal NPS test); C) I0 HIV+ with intracraneal occupying lesions (SOL)(5 Toxoplasma,3 Limphoma, l Progressive Multifocal Encephalopaty (PML), 1 Criptococcus). These lesions were diagnosed by a CT scan. SPECT was carried out with a Elscint SP4 camera. For reconstruction, a Butterworth (0.5,'6) filter was used, obtaining 2 pixel thick slices (4.5mm/px) in a 64x64 matrix. Results: All SPECT on group A were normal. On group 8 7 abnormal SPECT showed decreased rCBF mainly in frontal (5/7), temporal (4/7) lobes and white matter region (4/7). Of 9 abnormal SPECT from group C, 2 m a t c h e d with CT . In 7 SPECT, the focal lesions demonstrated by CT appeared as decreased activity regions in a context of diffuse supratentorial hypoperfusion. The normal SPECT corresponded to the patient with PME. Conclusions: i.- H M P A O S P E C T does not show impaired rCBF in HIV+ individuals without NPSI, but it does in HIV+ with NPSI, even if they have only 1 abnormal N P S test . 2.- In patients with SOL, EMPAO sPEnT seems to detect changes of rCBF in cortical regions that are not explained by CT scan images.The white matter region evaluation with HMPAO SPECT should be done carefully, because some lesions in this area could be mislead.

596

Herranz R.t

R. Peyron, L. Cinot~i, P. Ryvlin, D. Le Bars, J.C. Froment* F. Lavenne, F. Turjman*, F. Maugui~re. CERMEP & *H3pital Neurologique, 59 bd Pinel, 69003 LYON FRANCE. VISUALISATION IMPROVEMENT OF HIPPOCAMPAL STRUCTURES TO ASSESS TEMPORAL LOBE EPILEPSY }I;ITH POSITRON EMISSION TOMOGRAPHY. Hippocampal origin is frequently evoked in temporal lobe epilepsy (TLE). Usually, PET images are parallel to the orbito-meatal (OM) plane. We tried to improve the visualisation of the internal temporal lobe by orienting the slices according to the direction Qf the hippocampal plane (HP) from a MRI scan. Ten patients underwent sequentially MRI and PET in the saree plane.~ using a similar headholder and dedicated headmolds. 3D-MRI, T1 weighted, was performed at 1.5 Tesla. Sagittal planes provided the OM plane by registering external landmarks adn the OM-HP angle measure. Brain metabolism was studied using 18-Fluoro-deoxyglucose and data were collected using a 7 slices TOF-PET scanner. 14 exams were performed. In each, 14 intersperced slices were collected in 0 ~ and HP orientations. The OM-HP angle varied from 320 to 52° (mean 44°). Using this technique, the hippocampus delineation wds improved on both MRI and PET. On HP oriented PET images, the ability to detect abnormal metabolism was markedly increased since the ratio between hippocampal gray and neighbouring white matter went up to 50 % (mean 28 %) withrespectto the OM orientation. PET data should be acquired in the HP orientation when the hippocampus is suspected to trigger TLE. This approach remains valid even with 3D-PET scanners since the partial volume effect cannot be totally eliminated.

Monday, 2 September 1991

PO-2L1-77

PO-2L1-78

P.Colam~ssi, C~Cittanti, M.Giganti, F,Mascoli °, V,Bui* and A.Piffanelli Cattedra di Medicina Nucleate, Clinica Chirurgica °, Clinics Neurologica * - Univ.Ferrara - Italy

R Dierckx, M Maes, C $chotte, M Vandewoude, J Vandevivere City Hospitals of Antwerp, Born Bunge Foundation U.I.A. and University Hospital, Antwerp, Belgium.

A SPELT STUDY WITH 99mTc HM-PAO OF CEREBRAL BLOOD

FLOW BEFORE AND AFTER CAROTID ENDARTERECTOMY(EA) 40 asymptomatic patients one week before and after carotid EA were studied using 99mTc HM-PAO SPECT. All patients underwent CT, Eco-Doppler, angiography (8patients with bilateral stenosis) and neurological ex~mznation (NE) before and after surgeryThe evaluation of , rCBF was attempted by using qualitative a~alysis, semiq~antitative asymmetric index(SAI) and oortico-cerebsllar ratio (CCR). The results are summarized as follows: A) pre surgery evaluation: 26140 (65%)positive SPECT w l t h qualitatlve analysis. SAI and CCR showed 25140 (62.5%) and 28140 (70%) respectively. 4140 (I0~) demonstrated pre operative alterations on CT scan.0~iy the CCR identified bilateral lesions in patients with bilateral stenosis(8/8). NE resulted negative for pathological involvement of CBF in all patlents B) post surgery evaluation: qualitative method showed 19/26 (73%) patients with scintigraphic improvement of rCBF; SAI turned out to be less sensitlve 17126 (65%); CCR had 20126 (77%) improved patients and was able to identify controlateral changes.NE did not show clinical changes after surgery. We conclude that 99mTc IqM-PAO SPECT is a useful study to identify Datients with carotid disease and simultaneously rCBF changes.The CCR is more sensitive and able to detect hilatezal lesions. The post surgery study allows us to demonstrate that EA can improve cerebral perfusion and the use of the CCR can increase sensitivity.The NE, negative before and after surgery , does not allow us to evaluate the real o h n i o a l meaning of the scintigraphic findings.A long term follow 'up could better clear up this point.

TC-99m HMPAO DISORDERS

BRAIN

SPECT

IN

UNIPOLAR

DEPRESSIVE

Twenty-five drug-free patients presenting with unipolar depressive disorders were referred for perfusion SPECT as part of their investigation including EEG~ CT-scan, Hamilton depression scale, etc. According to DSM III criteria patients were classified as suffering minor depression {group I, n=8), major depression {group II, n= 12) and melancholia (group III, n=5). Acquisition was started 15 minutes after intravenous injection of 25 mCi Tc-99m HMPAO, using a single head LFOV rotating gan~na camera {Orbiter 75, Siemens) over 360 ° rotation with 64 views, 30 seconds per view. Activities in operator-defined ROIs of 3*3 pixels of left and right premotor frontal cortex , motor frontal cortexf parietal cortex , lateral temporal cortex and visual cortex were normalized to cerebellar activity. Data of the three groups were statistically compared with values of a reference group (group IV, n=4). Premotor frontal cortical activity was increased, while parietal cortical activity was decreased significantly in group II~ with patients suffering melancholia when compared with all other groups. Tentatively, the premotor frontal cortical hyperactivity may reflect obsessional selfreflection, characteristic of melancholia. T h e p a r i e t a l cortical hypofunction in melancholia, such as shown in our group, might present an a d d i t i o n a l b i o l o g i c a l similarity between melancholia and dementia of Alzheimer's type.

PO-2L1-79

PO-2L1-80

R Dierckx, A Dobbeleir, F Borqgreve, PP De Deyn, J Vandevivere Middelheim General Hospital, Born Bunge Foundation U.I.A., Antwerp, Belgium.

M. Domper, J. Arbizu, M.J. Garcia, J.C~ Ramires, A. Maldonado, J. Marti, J.A. Richter. clinics Universitaria. Facultad de Medlcina. Unlversided de Navarra. Avda. Pie XII s/n. pamplona (Spain)

THREE-DIMENSIONAL RECONSTRUCTION OF BRAIN PEP~USION Brainperfusion images were obtained with a three-head rotating gam/~a camera system (Triad 88, Trionix) equipped with a super-fine fan-beam collimator, sensitivity 102 counts/~Ci, min, system resolution 7.3 FWHM. Acquisition was started 15 minutes after intravenous injection of 25 mCi Tc-99m HMPAO. Projection data were accumulated in a 256-128 matrix, pixel size 1.8 mm, 60 seconds per angle, 40 angles for each detector (3 ° steps, 120 ° r o t a t i o n ) . Projection images were smoothed and reconstructed in a 128-128 matrix using a Butterworth filter with high cut frequency 0.7 cyc/Cm and roll off 5. Three-dimensional reconstruction was performed using a linear ray tracing through the volume with maximum pixel value rendering for visualisaticn of peripheral sulci and gyri. Activities of distinct gyri along the convexities of the frontal, temporal, parietal and occipital lobes as well as of cerebellar structures are shown. Clinical localisatory value is illustrated in a patient presenting focal temporal hyperperfusion associated with tumoral invasion . In another patient presenting with luxury perfusion three-dimensional display revealed the concentric aspect of the hyperperfusion around the infarction. Taking 4 minutes time, with the possibility of viewing the different angles in cin~-mode, three-dimensional reconstruction may routinely be performed for purposes of easy and quick anatomofunctional correlation of peripheral lesions.

S E M ~ U A N T I T A T ~ V E . ANALYSIS OF BRAIN SPECT. EVALUATION OF DIFFERENT INDEXES IN A L Z H E I M E R ' S D I S E A S E . Brain SPECT with 99mTc-HMPAO has been performed in 39 patients with Alzhsimer's disease (An) and in 19 healthy volunteers (HV). Diagnosis of AD was based on the criteria stablished by the NINCDS-ADRDA work group. These patients were divided into three groups according to the severity of the disease (mild, moderate, severe) evaluated by the score obtained in the Mini Examen Cognoscitivo by Lobe (MEC), which is a Spanish adaptation of the Mini Mental State Examination by Folstein: mild AD, MEC > 18 (n=9); moderate An, MEc = 8-18 (n=21); severe AD, MEc < 8 (n=9). Areas of interest were manually drawn on the reconstructed transversal slicesr in different cortical regions, cerebellum, and over the whole brain slice. Three kinds of indexes were calculated: cortico-cerebellar (Icc)~ cortico-occipital (Ice) and cortico-total (Ict), Statistical analysis was performed a p p l y i n g a Student's t test. In mild AD, none of the three indexes found differences with HV in the frontal region. Ice and Ice showed a significant decrease in the temporal region (p < 0.05) and parietal region (p <0.01), However Ict only found differences in the parietal region. In moderate and severe An, only Icc end !co showed a decrease in the frontal region. In temporal and parietal regions, the three indexes showed differences (p < 0.001). NO alteration was found in the occipital region. In conclusion, temporoparietal regions are the most affected in An, while the frontal region becomes affected as the severity of AD increases. The statistical significance of the indexes increases as the severity of AD does, being Icc the most sensitive index to these changes.

597

Monday, 2 September 1991

PO-2L1-81

PO-2L1-82

H. Fritzsehe, M . K . B e n z e r , E . H i l l b r s n d ~ P.KSnig. D e p a r t m e n t of Nuclear M e d i c i n e and P s y c h i a t r y I, L a n d e s k r a n k e n h s u s Feldkirch, Austria.

F. Grfinwald, G. Hefner, A. H u f n a g e l , B. O v e r beck, B. Briele, B. Ammari, C.E. Elger, H.J. Biersack. D e p a r t m e n t of N u c l e a r M e d i c i n e and E p i l e p t o l o g y , U n i v e r s i t y of Bonn, G e r m a n y

D2-RECEPTOR

IMAGING WITH SINGLE

HEAD ECT.

Imaging of brain receptors with SPECT gains i n c r e a s i n g interest in n e u r o l o g i c a l and p s y c h i a t r i c diseases. J - 1 2 5 - p y r r o l i d i n e - m e t h y l b e n z s m i d e (IMBZ) was shown to be an a d e q u a t e compound for D 2 - r e c e p t o r imaging. 5 mCi (185 MBq) were applied i.v. and a c q u i s i t i o n started after 40 min. with a s i n g l e - h e a d E C T - c a m e r a with a 3600 r o t a t i o n s 6 4 steps 50 see. each. Ratios oF c o u n t s / p i x e l From s t a n d a r d i z e d regions of the s t r i a t u m and frontal cortex were c a l c u l a t e d from summed t r a n s v e r s a l slices (19,5 mm thickness). Average ratios of D 2 - r e e e p L o r density in 7 healthy v o l u n t e e r s {6 m, I F; ~ = 40 a) were 1.54 - 1.90, x~= 1.77, and were equal to 9 p r o b a n d s (9 m; ~ = 44 a) 4 weeks after alcohol w i t h d r a w a l with ratios of 1.67 - 1.94, ~'= 1.75. In 12 u n m e d i c a t e d s c h i z o p h r e n i c s lower ratios were Found ( p < 0~05) in the range of 1.45 - 1.81; ~= 1.67. 18 n e u r o l e p t i c i z e d s c h i z o p h r e n i c s (9 m, 9 f; ~= 28 a) showed s i g n i f i c a n t l y lower ratios (p< 0,001) of 1.17 -1.65; ~= 1.57). A weak c o r r e l a t i o n of increase in n e u r o l e p t i e dosage and decrease of ratios was observed (r=-0,57). L e F t - h e m i s p h e r i c ratios were m o d e s t l y lower in c o n t r o l s (p< 0,18) snd more p r o n o u n c e d in n o n m e d i c a t e d and n e u r o l e p t i c i z e d schizophrenics (p < 0,08). Our results indicate s u f f i c i e n t quality of D 2 - r e c e p t o r imaging with IBMZ by single head ECT for w i d e s p r e a d use.The method may serve to control D 2 - r e c e p t o r density or blockade.

H.Herzogx, C.Unger 2, T . K u w e r t 1, H.G.Fischer 2, D.Scholz 1, W.Hollmannz, L . E . F e i n e n d e g e n ' (1) I n s t i t u t e of Medicine, R e s e a r c h Centre Jillich, and (2) I n s t i t u t e of Cardiology and Sports Medicine, Cologne, FRG NOT

INCREASE

CEREBRAL

This PET s t u d y was p e r f o r m e d to d e t e r m i n e if p h y s i c a l e x e r c i s e i n c r e a s e s c e r e b r a l glucose c o n s u m p t i o n (CMRglu) which might be e x p e c t e d from p r e v i o u s work showing i n c r e a s e d c e r e b r a l p e r f u s i o n (CBF) with e x e r c i s e and a coupling b e t w e e n CBF and CMRglu u n d e r p h y s i o l o g i c a l conditions. The u p t a k e of 18F-FDG was m e a s u r e d in 10 male p a t i e n t s with a h i s t o r y of m i g r a i n e aged 23 to 61 a t r e s t and w i t h i n 1 week a f t e r bicycle e x e r c i s e . The s u b j e c t s were f r e e of m i g r a i n e symptoms a t e a c h s t u d y time. The e x e r c i s e protocol a s s u r e d a c o m p a r a b l e load for e a c h p a t i e n t . FDG d a t a were c o n v e r t e d to images el local CMRglu (LCMRglu) u s i n g s t a n d a r d r a t e c o n s t a n t s . ROIs were d r a w n o v e r t h e c e r e b e l l u m and c o r t e x in 4 p r e s e l e c t e d slices. The m e a n LCMRglu (in iJmol/min/100g) a v e r a g e d o v e r all ROIs and s u b j e c t s did not c h a n g e s i g n i f i c a n t l y (p>O.05) r a n g i n g from 39.7+_8.6 d u r i n g r e s t to 30.0+_4.3 d u r i n g e x e r c i s e , t h e former f i n d i n g not being s i g n i f i c a n t l y d i f f e r e n t from t h e mean LCMRglu of 36.9+_4.6 m e a s u r e d in 13 r e s t i n g normals. I n d i v i d u a l ROIs showed m e a n d e c r e a s e s from 1.7% to 19% b e t w e e n r e s t and e x e r c i s e . Only t h e v i s u a l c o r t e x i n c r e a s e d (5%), p e r h a p s due to visual fixation during exercise. In conclusion, in c o n t r a s t to t h e r e p o r t e d e x e r c i s e i n duced i n c r e a s e of CBF, t h e p r e s e n t s t u d y r e v e a l e d e v e n a t r e n d of d e c r e a s e of global CMRglu. This s u g g e s t s an u n c o u p l i n g b e t w e e n CMRglu and CBF u n d e r e x e r c i s e which may r e l a t e e i t h e r to a m e t a b o l i c i n t e r v e n t i o n e.g. by f o r m a t i o n of l a c t a t e a n d / o r to an o v e r a l l d e c r e a s e in m e n t a l a c t i v i t y d u r i n g p h y s i c a l exercise.

598

The a i m of the s t u d y was to c o m p a r e the value of J-123-Iomazenil-SPECT with Tc-99m-HMPAOSPECT in the presurgical evaluation of patients with m e d i c a l l y i n t r a c t a b l e seizures. I o m a z e n i l - S P E C T was p e r f o r m e d in 21 patients 90 min p.i.. 18 p a t i e n t s had l a t e r a l i z e d EEG c h a n g e s . This r e g i o n is a d d r e s s e d as focus. In 13 Of these 18 cases Iomazenil-SPECT showed a d e f e c t on the focus side, in 2 c a s e s on the contralateral side and in 3 cases no a b n o r mality. I n t e r i c t a l H M P A O - S P E C T had b e e n performed in 13 of the 18 ~ a t i e n t s and a g r e e d in 5 cases with the EEG. In 3 patients lesions w e r e found o n l y c o n t r a l a t e r a l to the focus including the 2 cases with IomazeniI-SPECT/EEG divergence. In 3 c a s e s H H P A O - S P E C T s h o w e d no a b n o r m a l i t y a n d in 2 c a s e s b i l a t e r a l lesions. In 2 p a t i e n t s w i t h b i t e m p o r a l E E G foci I o m a z e niI-SPECT s h o w e d one lateralized lesion and one n o r m a l result, w h i l e the H M P A O - S P E C T revealed bilateral lesions in b o t h cases. One patient with generalized EEG changes showed a normal Iomazenil-SPECT. H M P A O - S P E C T was not p e r f o r m e d in this p a t i e n t . It is c o n c l u d e d , that I o m a z e n i l - S P E C T c o r r e l a tes s l i g h t l y h i g h e r w i t h the E E G focus than HMPAO-SPECT. Whether this i n d i c a t e s a h i g h e r d i a g n o s t i c v a l u e of th~s m e t h o d has to be det e r m i n d e d by p o s t o p e r a t i v e e v a l u a t i o n of the patients.

PO-2L1-84

PO-2L1-83

PHYSICAL EXERCISE DOES GLUCOSE CONSUMPTION

S P E C T W I T H I O M A Z E N I L A N D H M P A O IN E P I L E P S Y

J.Hierholzer, W.Poewe*, M.Cordes**, L.Schelosky*, G,Barzen, R.Felix Dpts. Radiology and Neurology*, Institut fiir Diagnostikforschung**, UKRV-C, Freie Universit~it Berlin DOPAIVlIN D2 RECEPTOR IMAGING IN PATIENTS WITH PARKINSON'S DISEASE

The pharmacologic effects of neuroleptic drugs, such as antipsychotic and extrapyramidal effects, are khown to be basicly due to the blockade of central nervous system Dopamin D2 receptors. Since alterations in striatal D2 receptor density and/or .function are i n v o l v e d in a n u m b e r of m o v e m e n t disorders m e a s u r e m e n t s of D2 receptor occupancy by SPECT using ~ Z 3 J o d i n e - l a b e l e d Iodobenzamide (IBZM) is of high potential clinical value. l'he goal of our study was to evaluate I123-IBZM-SPECT as a tool to determine D2 receptor density in patients with Parkinson's disease. Therefore 10 patients were studied. After a dynamic acquisition 0-20 rain p.i. two SPECT series were performed 30 min and 80 min p.i. of 5 mCi I n 3 - I B Z M . . Visual and quantitative evaluation by ROI-technique of transaxial, coronal and sagittal slices with and without attenuation correction (0.122). Signal intensity within the basal ganglia (BG), parietal cortex (PC) and cerebellum (CB) was measured and ratios calculated. In addition an approximate global brain uptake was calculated. 7/10 patients showed high accumulation of the radioligand in the basal ganglia. A significantly reduced uptake was found in 3/10 patients who were on a therapeutic regime with D2 receptor ligand Lisurid. In one patient we were able to assess cerebral D2 receptor binding before application of Lisurid and a second time under therapeutic Lisurid serum levels. In conclusion I123-IBZM has proven it's usefulness in assessing D2 receptor status in patients with dopamin related extrapyramidal disorders as well as potential dynamic changes of BG-D2 receptor occupancy by 1123IBZM.

Monday, 2 September 1991

PO-2L1-85 J. Hierholzer, K.Rosenkranz, G.Barzen, A.Debrand-Passard, M. Cordes**, J.Palenker*, R. Felix, Dpts. Radiology and Surgery*, Institut ffir Diagnostikforschung**, UKRV-C, Freie Universitiit Berlin ASSESSMENT OF CEREBROVASCULAR AUTOREGULATION IN PATIENTS WITH CAROTID ARTERY STENOSIS BEFORE AND AFFER THROMBENDARTERIECTOMY; Tc99m-HM-PAO-SPECT vs. TCD. Postoperative changes of regional cerebral blood flow (rCBF) in patients with unilateral stenosis of the internal carotid artery (ICA) before and after t h r o m b e n d a r t e r i e c t o m y (TEA) were studied by T c 9 9 m - H M P A O - S P E C T and by transcranial Doppler-ultrasound (TCD) before and after stimulation with Acetazolamide (DIAMOXR). 10 patients with unilateral ICA-stenosis ( > 80%) underwent T c 9 9 m - H M - P A O - S P E C T before and 2-5 days after TEA for evaluation of r-CBF. Cerebrovascular autoregulation (CVA) was assessed by stimulation with DIAMOX R. Results were compared with those obtained by TCD. 5/10 pts. showed a significant decrcase in rCBF, 5/10 an impaired CVA and on TCD 3/10 pts. presented with reduced increase of the mean velocity (Vmean) in the middle cerebral artery (MCA) in the hemisphere corresponding to the carotid stenosis as compared to the unaffected side. In all 10 pts. Doppler and angiographic findings were normal after TEA. 2/10 pts. postoperatively showed improved rCBF, and 2/10 improved CVA whereas 3/10 pts. had unchanged reduced rCBF and 2/10 unchanged impaired CVA. Changes of r-CBF and CVA in pts. who underwent TEA for unilateral ICA-stenosis can be measured and quantified by HM-PAO-SPECT and by TCD before and after stimulation with D I A M O X R. While other diagnostic procedures (Doppler, a n g i o g r a p h y ) detect i n t r a v a s c u l a r b l o o d v o l u m e of the main intracranial blood vessels, H M - P A O - S P E C T documents intracellular tracer accumulation in the brain and therefore capillary tissue perfusion. HM-PAO-SPECT for that reason, beeing more sensitive in d e t e c t i n g r e g i o n a l cerebral blood flow changes, should always be part of the angiologic work-up.

PO-2L1-86 J.Hierholzer, U.Keske, F.Ferstl, B.Schmitz*, M.Cordes**, G.Barzen, R.Felix Dpts. Radiology and Neurology*, Institut ftir Diagnostikforschung**, UKRV-C, Freie Universit~it Berlin BENZODIAZEPIN RECEPTOR IMAGING IN PATIENTS WITH EPILEPTIC SEIZURES Benzodiazepin (Bz) are widely used clinically and are effective agents in the treatment of various neurologic and p s y c h i a t r i c d i s o r d e r s . T h e r e f o r e an a l t e r a t i o n of the Bz/GABA-receptor complex sensitivity or -density has been postulated -and in the meantime observed- in disease states where these drugs are of therapeutic value. 1 2 3 I o d i n e - l a b e l e d Iomazenil (Ro 16-0154), a Bz-receptor antagonist derivate of Flumazenil, has resently proved to serve as an imaging agent for living brain B Z - r e c e p t o r densitiy. In our study we examined a total of 40 patients with primarily unclassified epileptic seizures. SPECT was p e r f o r m e d 60 rain after i.v.-injcction of 6 mCi i 1 2 3 _ IomazeniI on a rotating gamma-camera. Transaxial, coronal and sagittal slices were reconstructed from the obtained data. Images were evaluated visually and quantitatively in ROI-technique. Results were compared to those obtained by EEG, CT, MRI. Additionally T c 9 9 m - H M - P A O - S P E C T was performed in all patients to assess regional cerebral blood flow. In paticnts with temporal lobe epilepsy results indicate a g o o d c o r r e l a t i o n between the presumed epileptic focus defined by EEG and an aerea of decreased Bz-receptor density in the human brain. No significant reduction of Bz-receptor density had been observed in patients with frontal lobe epilepsy. In c o n c l u s i o n I123-1abeled Iomazcnil d e m o n s t r a t e d high diagnostic usefulness in the clinical work-up of patients with epileptic seizures.

PO-2R1-1

PO-2R1-2

M.Aas*, D.J. Hnatowich, G. Mardirossian, T.W. Griffin, A. Salimi, T. Ito, H.S. Bushe, R.W. Atcher**, J.J. Hines**, and A.B. Brill. *The Norwegian Radium Hosp., Oslo, Norway, Univ. of Mass. Medical Center, Worcester, MA, USA, and **Argonne National Laboratory, IL, USA.

Batchelor.

II4mln-LABELED B72.3 IgG IN TUMOR-BEARING NUDE MICE. LONG-TERMBIODISTRIBUTION STUDY AND RADIATION DOSIMETRY

An extensive study has been performed of the distribution of radiation dose across the hands of staff who formulate, dispense end administer diagnostic doses in Nuclear Medicine. With possible forthcoming reductions in dose limits, it is important that as much data as possible is available on such dosemetry. It is also essential to keep all doses as low as reasonably ad,~vable and to accurately assess the doses of staff who may approach three tenths of the extremity dose limit. Special "dosemeter gloves" were made each consisting of 9 thermoluminescent dosemeters (TLDs) located at various positions on each hand. An o p t i m a l s i t e can be identified for each manipulation performed (ie formulation or dispensing of the radiopharmaceutieal) which truly reflects the mean extremity dose. Although the use of syringe shields in reducing such doses has been well documented~ the technique of prior insertion of butterfly cannulae has not been carefully evaluated. The dosemeter gloves were used to assess the dose reducing potential of employing different types of butterfly cannula. The dosemeter location, which consistently gave a reading closest to the mean whole hand dose, was at the base of the second digit. (Tables, illustrating regional variation ofabsorbed dose for both hands are presented). The mean whole hand dose was reduced to 47% for the left handand 72% for the right hand when using certain butterfly cannula. It was also found that the difference between the left hand and right hand dose during dispensing was much less when using butterfly administration technique.

The aim of the study was to assess the possibilities of using the long-lived indium isotope, ll~In (halflife 50 days), for radiation therapy. Murine B72.3 IgG monoclonal antibody was labeled with [~mln via DTPAcoupling while chimeric antibody was labeled via both DTPA and a macrocycle. The labeled antibodies were given i.v. to three groups of nude mice bearing human tumor xenografts (LS174T) subcutaneously. Four to six animals in each group were sacrificed from 3 to 36 days after injection of radiolabeled antibody. Tumor, blood and organ concentration of radioactivity was recorded. Although the biodistribution in the three groups of animals showed great similarities, there were important differences. Administratio~ of the DTPA-coupled chimeric antibody led to higher activity in tumor and lower in liver and bone as compared to DTPA-coupled murine antibody. Administration of the macrocyclecoupled chimeric-6ntibody also led to higher activity in liver and bone as compared to DTPA-chimeric, while no significant differences in tumor uptake and clearance rates were found between these two groups. Whole-body autoradiography showed that after 1 week the radioactivity was concentrated in the outer part of the tumor, while after 3 weeks it had a more patchy distribution throughout the tumor with lowest concentration in the periphery. Radiation doses were calculated based on measured organ radioactivity neglecting source to target contribution. The tumor/non tumor dose ratio was marginally favorable for therapy in the group injected with DTPA~coupled chimeric antibody.

D.

Webber

S, Baldock.

C, Penfold. A, Aric.

I, H~ggins.R

St. Thomas' Hospital, lONDON

THE MINIMISATION AND DISTRIBUTION OF RADIATION DOSE TO THE HANDS TO STAFF IN NUCLEARMEDICINE

599

M o n d a y , 2 S e p t e m b e r 1991

PO-2R1-3

PO-2R1-4

Do~an BOR*, Serdar OZQELiK, Hikmet BAYHAN" *Nuclear Training and Research Center Turkish Atomic Energy Agency, Ankara/TURKEY "*G01hane Military Medical Academy and Faculty, Ankara/TURKEY

A. DOBBELEIR, R. DIERCKX, J. VANDEVIVERE. M i d d e l h e i m General Hospital, Antwerp (Belgium).

A TECHNIQUE FOR THE REMOVAL OF RING ARTEFACTS IN SPECT IMAGES Circular artefacts in tomographic images are created from the variations in SPECT planar uniformity and their magnitute increases as the distance between the center of rotation (COR) and planar non-uniformity decreases. Flood correction technique is the common method for the correction of non-udiformities, but special care must be taken during the preparation of source and acquisition of correction image.

A simple non-uniformity correction technique was developed for SPECT. The x and y coordinates of the defective pixel in the planar matrix is found from the ring radius and its pssition over the -y- axis of the detector. The width of the ring gives the numbe¢ of defective pixel in the planar data. Following the measurement of the ring artefact amplitude (At), a correction factor proportional 1o the planar artefact amplitude (Ap) is obtained from the At vs. Ap relation and is used to change the count content of the defective pixel in the planar matrix. In order to simumte the detector non-uniformities, various artefacts of different size and amplitudes have been created at the COR and different radius in the planar images of a cylindrical phantom. A series of relations are then obtained between the amplitudes of planar and their corresponding ring artefacts. Once the tomographic acquisition of a cylindrical phantom with high count statistic is performed, these relations can be used for the correction of tomographic ring artefacts. This technique gives an absolute correction and eliminates the problem of flood correction methods. We have also demonstrated the superiority of this technique in correction the artefacts of TI-201 images, where the tomographic artefact amp!itudes are much higher and could not be removed completely by the other correction methods.

PO-2R1-5 P.R. Franken, A. Dobbeleir, R.Ranquin, J.Vandevivere. Middelheim General Hospital, Antwerp (BELGIUM). FAST-DYNAMIC SPECT MYOCARDIAL IMAGING USING A THREE-DETECTOR SYSTEM. The three-detector SPECT system (TRIAD) manufactured by TRIONIX has been used to assess its basic performances for fast-dynamic SPECT imaging of the heart. For that purpose, the system was equiped with general purpose parallel-hole collimators (sensitivity: 337 cts / I~Ci.min FWHM 15 cm with scatter: 14.0 ram). Data were acquired in continuous body-contour rotation mode with a rotation speed of 30 seconds and framed into 6 ° intervals. By repeating rotation in alternate directions, serial data were acquired for 10 minutes immediately after I.V. injection of 30 mCi Tc99m SESTAMIBI in 5 patients with recent myocardial infarction. A 9-point smoothing was applied to the projection data. Images were reconstructed into a 64x64 matrix using a filtered backprojection algorithm (Hamming filter with a cutoff frequency of 0.7 cycle / cm) and reoriented according to the ventricle long axis. The slice thickness was 7.12 mm. SPECT images obtained within the first minute after injection show artifacts due to first pass effects. Images of sufficient good quality for drawing regions of interest were obtained in all patients. The pixel count density averaged 72 counts in the noninfarcted myocardium and 40 counts in the infarcted myocardium. Myocardial and blood pool time-activity curves demonstrated rapid blood clearance of Tc-SESTAMIBI and myocardial uptake reaching a plateau 3 to 5 minutes after bolus injection. The coefficient of variation between individual measurements during the last 5 rain averaged 4.3% for normal and 7.1% for infarcted myocardium. We conclude that good quality serial myocardial imaging and time-activity curves can be obtained with acquisition time of 30 seconds using this three-detector SPECT system.

600

HIGH SPATIAL RESOLUTION SPECT USING R O T A T I N G G A M M A C A M E R A AND S U P E R FINE COLLIMATORS.

A THREE-HEAD LEAD F A N - B E A M

A t h r e e - h e a d r o t a t i n g SPECT s y s t e m (TRIONIX TRIAD) was t e s t e d in o p t i m a l and c l i n i c a l c o n d i t i o n s , We c o m p a r e d ultra-high resolution p a r a l l e l and fan-beam collimators made of lead. The spatial resolution was 7.3 ~m FWHM for the fanbeam collimator (i0.1 ram p a r a l l e l ) a n d the v o l u m e s e n s i t i v i t y w~s 0.4 k c p s / ~ c i / m l / c m (0.9 k c p s / ~ c i / m l / c m parallel) u s i n g a 20 cm d i a m e t e r u n i f o r m c y l i n d e r filled with Tc-99m. At high count density, tomographic images of a Jaszozak Deluxe p h a n t o m resolved the 6.4 ram rods with an image contrast of 57% for the fanbeam (7.9 ram, 50% for parallel). SPECT images of the Jaszczak Deluxe phantom were obtained with count d e n s i t i e s s i m i l a r to a p a t i e n t study (i GBq T c - 9 9 m HMPAO,25 min acquisition time).The reconstruction filter was adapted keeping the root-mean-square noise less then 7% in the reconstructed image~. The sphere of 12.7 ram was visible with an image contrast of 65% using the fan-beam collimator (12.7 ram, 49% parallel and 15.9 ram, 35% parallel one detector acquisition). W i t h c o u n t d e n s i t i e s s i m i l a r to a 40 m i n p a t i e n t acquisition the 9.5 ram sphere became visible with 44% image contrast using fan-beam collimators. P e r f u s i o a b r a i n s t u d i e s were a c q u i r e d in a 256-128 matrix, 3 ° step and 60 sec/image. Projection data were r e c o n s t r u c t e d in a 128-128 matrix using a Butterworth f i l t e r (high cut freq 0.7 cyc/em, roll off 5). The p e r f u s i o n images d i s t i n g u i s h e d str~ctures as the head of the caudate nucleus, the p~tamen and the insula.

PO-2R1-6 GARDIN I, COLAS LINHART N, PETIET A, BOK B. Department of Nuclear Medicine, Hospital Beaujon, F-92110 Clichy, FRANCE.

DOSIMETRY AT THE CELLULAR LEVEL OF KUPFFER CELLS AFTER Tc 99m SULPHUR COLLOID INJECTION. The radiation dose to Kupffer cells was estimated at the cellular level, after IV injection of Te-99m labelled sulphur colloids in rats. The results were then compared with those obtained using classical dosimetry. From the microscopy appearance observed using a "track" microautoradiographic method, it was shown that only 0.2 % of the Kupffer cells were actually involved in the pinocytosis of radioactive colloids. For each electronic emission from T c - 9 9 m , the fraction of the emitted energy absorbed within the Kupffer cell was calculated using the values provided by Berger (1973). About 15 % of the total energy emitted by electrons was autoabsorbed in 0.2 % of the Kupffer cells. The dose due to photons is negligible for labelled Kapffer ceils if compared to the electron dose but contributes significantly to the irradiation received by the other liver cells. If these results are extrapolated to humans, the dose absorbed b y the la'belled cells can be estimated between 0.5 and 0.9 Gy/MBq. This represents about 5,000 times the average dose to the remained liver as estimated from classical dosimetric methods. In cases like this one with evidence of an important distribution heterogeneity, dosimetric estimations at a cellular level are mandatory. BERGER MJ. Improved point kernels for electrons ~nd beta ray dosimetry. Washington DC, US Department of commerce, National Bureau of Standards, NBSIR 73-107 (1973).

Monday, 2 September 1991

PO-2R1-7 G Germano* ", EJ Hoffman', M Salvatore* * "

Istituto "Fondazione Senatore Pascale", 80100 Napoli, Italy Division of Nuclear Medicine and Biophysics, UCLA School of Medicine, Los Angeles 90024, USA

A SIMPLE, MACINTOSH-DRIVEN DATA ACQUISITION SYSTEM FOR NUCLEAR MEDICINE APPLICATIONS. We have designed and assembled a eustomizable, modular data acquisition system for the benchtop testing of detectors and electronics used in nuclear medicine instrumentation. The setup consists of standard NIM and CAMAC modules (amplifiers, discriminators, ADCs, etc.) controlled by a Macintosh IIcx through a commercially available interface board (NB-GPIB, National Instruments, TX). GPIB-CAMAC interfacing takes place inside the CAMAC crate controller. Direct memory access (DMA) allows data acquisition and transfer speeds of up to 1 MHz. Simple operation of the system is possible through the graphical user interface provided by Labview2TM,an object-oriented program (OOP) based on the dataflow-type language G. In G, software modules (also termed virtual instruments, or VIs) simulate the look and feel of an instrument's front panel on the computer screen, so that intuitive mouse manipulations allow to control that instrument. The often complex protocols required to communicate with the hardware modules are effectively hidden in subroutines (sub-Vls). We have developed a good number of graphical software modules for various nuclear medicine applications. For example, a VI has been created to automatically acquire, calculate, display and balance the pulse-height spectra of the photomultiplier tubes in the 4x8 bismuth germanate (BGO) detector matrix used in current Siemens ECAT 831/931 PET scanners. Other applications include the comparative analysis of different detector materials and the study of the effect of pulse shaping on nuclear signals. The total cost of our system is very limited compared .to similar, virtual instruments based approaches using minicomputers. In conclusion, we expect personal computers to gain an increasingly larger role in data acquisition, instrument control and laboratory automation in the future.

PO-2R1-8 L. Hahn, D. Swerhone, B. Gladman, R. Kloiber, A. Crawley. Department of Radiological Sciences and Diagnostic Imaging, Foothills Hospital, Calgary, Alberta, Canada GAMMA CAMERA BASED CONE BEAM TRANSMISSION TOMOGRAPHY AND ITS APPLICATION TO SPECT Non-uniform attenuation compensation of SPECT images is potentially important when quantitative information is required. The best results in compensating these effects are obtained when applying maps of attenuation coefficients representing the tissues in those parts of the body being imaged. It has been shown by S.H. Manglos, et al, (1990) that it is possible to obtain high quality Cone Beam Transmission Tomography (CB-TT) images using an uncollimated rotating gan~na camera and a point source of activity located at some distance from the detector. These images map the attenuation coefficients in the body and can successfully be used for correction of effects of non-uniform attenuation. We have used the ADAC GENESYS gamma camera with removed collimator to obtain attenuation coefficient maps in non-uniform phantoms (chest and pelvis) and in one volunteer (head and chest). The point source containing 14 MBq of Tc-99m was located opposite to the detector on the gantry, 64 cm from it. Data were acquired during 5 minutes. The CB-TT reconstruction used a cone beam filtered backprojection algorithm to generate 32, 64 x 64 slices. The attenuation maps obtained have superior resolution and after proper scaling can be used for removal of image distortion due to non-uniform attenuation. i. Manglos S.H., et al: Attenuation Maps for SPECT Determined Using Cone Beam Transmission Computed Tomography, IEEE TNS, 37, pp. 600-608, (1990).

PO-2R1-9

PO-2R1-10

V. H u ~ , P. H r a d i l e k , M. L d z n / ~ e k Department of Nuclear Medicine, University ospital, 01omouc, Nuclear Research Institute, eL near Prague, Faculty of Pharmacy, Hrsdec Kr~Iow~,CSFR ARSORaED DOSE ESTIMATES FOR 1-131-MIBG

U. J~er, J.RuckEaber* , F. Bitter*, M. Litzka z, P. S c ~ d l i n 3, B. Bihl, W.E. A d a ~ Katharinenhospital Stuttgart, Klinik f~r Nuklear~mdizin ZUniversit~t Ulm, Abt. Nuklearmedizin 2Universit~t Ulm, Mikroelektronik , ~DKFZ Heidelberg Quantitative Analysis of Iterat/ve SPECT-Reconstzuction and Filtered Backprojecti~

Iodine-131-Meta-iodobenzylguanidine w a s prep a r e d in Nucl. Res. I n s t i t u t e , Re~. I n o r d e r to i n t r o d u c e this s u b s t a n c e i n c l i n i c a l use in ~SFR, b i o k i n e t i c d a t a c o l l e c t e d in m a l e r a t s (Farm. Fsc., H r s d e c K1n~lov~) and in pat i e n t s (Dept. o f Nucl. M e d . , U n i v . Hosp., P r a g u e - M o t o l , I n s t . o f ' B i o p h y s , a n d Nucl. M e d . , M e d . F s c . , P r a g u e a n d D e p t . e f Nucl. M e d . , N a t i o n . O n c o l . Inst.~ B r a t i s l s v 8 ) w e r e u s e d f o r the c a l c u l a t i o n e f a b s o r b e d dose in v s l~ious o r g a n s . The c u m u l a t e d a c t i v i t i e s in h u m a n o r g a n s w e r e t r s n a f e r e d f r o m t h ~ s e in r a t o r g a n s u s i n g the f o r m u l a by E r t l e t al." The calculstio~n o f d o s e s w a s p e r f o r m e d according to s t a n d a r d M I R D technlques. The w h o l e body r e t e n t i o n o b t a i n e d f r o m the h u m a n e x c r e t i o n d a t a a g r e e s w e l l ~ i t h the l i terstua-e. The f o l l o w i n g s b s Q r b e d d o s e s to i n d i v i d u a l o ~ g s n s w e r e c a l c u l a t e d (mGy/MBq) : k i d n e y s 0 . 1 2 3 : l u n g s 0.157. b l a d d e r w a l l 0.4~ testes O . 0 6 7 ; ' s m a l l i n t e s t ~ 0.36j l a r g e in" test. 0.212; s t o m a c h w a l l O.lllj s p l e e n 0 . 1 6 ~ liver 0.121; a d r e n a l s 1.22. D o s e s i n the f i r s t f o m m o r g a n s c o m p a r e w e l l w i t h other dose e s t i m a t e s i n c l u d i n g I C R P P u b l i c a t i o n 53; ho~ w e v e r , this does not h o l d true f o r e t h e r o~gans. Measurements made in ~'R as w e l l as lit e r a r y d a t a S U g E e s t that the I C R P 53 v a l u e o f 0 . 8 3 m G y / H B q in l i v e r i s e x t r e m e l y h i g h and 0 . 1 7 m G y / M B q i n a d r e n a l s too low. W e b e l i e v e that a t h @ r o u g h r e v i s i o n o f I C R P 53 d a t a on I ~ I 3 1 - M I B G ia needed. Nucl. M e d . C o m m . 8 : ~ 3 - 6 5 ~ , 1 9 8 7

The method of Iterative SPECT Reconstruction (ISR) was tested with a special multifunctional SPECT-Test object consisting of 4 areas : 6 zylindrical rods, uniform area, active linearity grid and 2 crossed linesources of 3 m diameter. The SPECT-Acquisition parameters are the same as in clinical use. The parameters : uniformity (IH), linearity (LI), system resolution (SR), contrast (CO), deviation of the diameter (DD) and shape (SD) were analysed for the iteration steps n-i...30 and for two common filters of the FBP-method. The results are discussed depending on the number of iteration steps. The theoretical limits corresponding with the matrix size and the method are discussed by use of a mathematical test object [Table 1 :faR(math) ]. The influence of the system resolution and attenuation is discussed. First clinical examples of HMPAD- and MYOCARD-SPECT are shown. Parameters IH [%] LI [ram] SR [~] 10 iron rod: CO [%] DD [%] DS [%]

ISR(math) I ISR(n=II)

FBP

9.8 2.4 15.3

10.4 5.4 16.1

11.5 6.5 23.1

99.2 38.0 3.1

65.1 51.0 3.9

52.8 139.0 4.1

Tab. Comparison of ISR and FBP ISR(math) : Theoretical limit by use of a 64x64 matrix ISR(n=ll) : ISR with ii iteration steps : FBP with a Butterworth Filter (n=5,c-0.4 Ny) FBP

601

Monday, 2 September 1991

PO-2R1-11 Archibald, University

PO-2R1-12 A and Khan, 0 o f the West I n d i e s

M.V. Knopp, H. Ostertag, J. Doll, L.G. Strauss, H. Hoverath, U. Haberkorn, W. Kuebler, F. Oberdorfer, G. van Kaick Institut for Radiologie und Pathophysiologie Deutsches Krebsforschungszentrum, Heidelberg, FRG

NUCLEAR MEDICINE IMAGING IN TRINIDAD AND TOBAGO INITIAL EXPERIENCE: A. ARCHIBALD AND O. KHAN Since J u l y 1990 a t o t a l of 190 p a t i e n t s (ages 3 months - 80 y e a r s ) w i t h a v a r i e t y of clinical c o n d i t i o n s were r e f e r r e d f o r n u c l e a r m e d i c i n e imaging i n v e s t i g a t i o n s f o l l o w i n g the installation o f a Siemen's O r b i t e r I I gammacamera-comPuter system, the f i r s t s t a t e of the art n u c l e a r imaging u n i t to be i n t r o d u c e d i n t o T r i n i d a d and Tobago. This paper d i s c u s s e s our i n i t i a l experiences, problems and the response of the medical community f o l l o w i n g the i n t r o d u c t i o n of t h i s imaging m o d a l i t y . ( T e c h n i c a l d i f f i c u l t i e s i n c l u d i n g problems o f i m p o r t a t i o n and h a n d l i n g of r a d i o a c t i v e m a t e r i a l w i l l a l s o be d i s c u s s e d ) . Cancer p a t i e n t s w i t h a v a r i e t y of p r i m a r y tumours r e f e r r e d f o r the e v a l u a t i o n of metastatic disease, crucial for staging, monitoring and t r e a t m e n t c o n s t i t u t e d the s i n g l e l a r g e s t referral group. Imaging of the b r a i n ( 5 0 ) , t h y r o i d ( 2 2 ) , h e a r t ( 2 5 ) , bone ( 5 1 ) , k i d n e y ( 1 5 ) , l i v e r and biliary t r e e and of the m e d i a s t i n u m ( 2 0 ) , were a l s o performed u s i n g Technetium 99m, I o d i n e 131, T h a l l i u m 201 and G a l l i u m 67, as r a d i o n u c l i d e s in the a p p r o p i a t e c l i n i c a l c o n t e x t . The use of 1-131 f o r the t r e a t m e n t of t h y r o i d cancer and t h y r o t o x i c s t a t e s was a l s o performed in 8 patients.

PO-2R1-13

MEDICAL ASPECTS OF OUANTITATION iN WHOLE-BODY PET Ouantitation of PET images has been done since the introduction of PET-Scanners, but we find quite different approaches and considerable disagreement on the most appropriate techniques. Once all physical aspects of quantitation are resolved, medically relevant aspects have to be considered as well and their influence on the quantitation. We reviewed more than 100 whole-body PET studies and determined potential as well as common problems. The most obvious problem is patient (object) movement due to physiological reasons, like respiratory as well as cardiac movement and motion due to non-compliance of the patient during the study. If significant motion occurs, different effects can be seen if it happened between transmission and emission scan or just only during the emission scan. The physiological state of the patient significantly influences the uptake of metabolically active compounds like FDG whereas the perfusion time can be influenced by heartrate and bloodpressure. Another important aspect is the inconsistency of the selected procedure for the study. Whereas changes in dose and time of a study can be mathematically corrected, variations due to differences in precompared to post-injection transmission scans and different patient positioning like arms above the head compared to beside the body results in more demanding correction techniques. We can conclude that a detailed knowledge of potential interferences due to physiological or patient as well as procedure dependent variations is necessary in order to enable reliable and accurate quantitation of whole-body PET studies even when all physical aspects have been considered.

PO-2R1-14 M.F. L o m a n o v of T h e o r e t i c a l Experimental Physics, MOScoW, U S S ~

W.J.M.Lenglet, S.R.de Boer, R.M.Heykoop, A,Jipping Dept. Nuclear Medicine and Medical Physics KCL, Leenwarden, The Netherlands A n~ q--lqty control system to r e s o l u t i o n and s ~ - - ~ t i v i t y

and

f o l l o w up systel

As part of an extended quality control program a new phantom and dedicated software has been developed at our institute. The main purpose of this project is to determine both the system resolution (FWHM) and the effect of attenuation and scattering on the sensitivity. Seven disposable tubes are positioned along the diagonal of a solid perspex phantom, each at a different well defined distance to the collimator surface. The phantom can be positioned parallel to either the x- or y-direction of the gammacamera. Profile scans containing a maximum of 7 line spread functions (LSF) are recorded on a stand-alone Multi Channel Analyzer (MCA); therefore a dedicated unit has been developed to interface the analog camera output (X, Y, Z) directly to the MCA. This analog data registration is preferable to the standard digital mode (i.e. 256 x 256 matrix) due to the improved detection accuracy (analog 0.I mm/ch; digital 1.5 mm/ch). A standard RS232 port is used to transmit the recorded data to our Nuclear Medicine uPDP-II computer system using a commercial available communication protocol. The data are automatically analyzed and both the FWHM (mm) and the sensitivity (pulses/desintegration) are calculated and stored in a database. The described procedure is performed on every gammacamera for all our collimators. Reproduceability of our camerasystems (i.e. especially collimator performance) can be checked by repeating those measurements on a frequent basis. Results will be presented.

602

institute

Prospects of N u c l e a r M e d i c i n e for P r o t o n R a d i a t i o n T h e r a p y Among the new developments

of l a r g e

treatment

accelerators

centers

with

proton

Application medical the

project that has been actively realized in I T E P s t a n d s o u t for t h e f a c t t h a t a c c e l e r a t o r s are t o be used in o n e c o m m o n c e n t e r not only as t h e m e a n s for b e a m p r o t o n t h e r a p y b u t also for P E T d i a g n o s t i c s . The advantages of p r o t o n b e a m s u s e d i n r a d iotherapy lie in the possibility of l o c a l i r r a d i a t i o n of p a t h o l o g y c e n t e r s , t h e surrounding organs and tissues being protected from irradiation. A l o n g s i d e with solving traditional diagnostic problems,PET may be used in radiation therapy dose planning,contributing to topometry with evaluation of t h e f u n c t i o n i n g volumes for t h e o r g a n i n w h i c h a c e r t a i n p a r t s is to be protected from irradiation. In addition,a possibility exists for the correction,since the radiation therapy course u s e of i n d i c a t o r s labelled by ultrashortlived i s o t o p e s of b i o g e n e o u s e l e m e n t s a l l o w s for r e peated research due to low radiation load,high s p e c i f i c a c t i v i t y , etc. T h e t i s s u e responce to may be registered much earlier irradiation t h a n t h e r e s u l t s of b i o p s y r e s e a r c h c o m e out. Together with the application in ontology, some unusual treatment methods Cendocrinous disorders,vascular brain malformation) is c a r ed out thus confirming wide possibilities for development of n e w d i r e c t i o n s in proton therapy and in positron nuclear diagnostics.

Monday, 2 September 1991

PO-2R1-15

PO-2R1-16

H.J. Ostertaq, W.K. K0bler, J. Dolt, H, Hoverath, S. Ziegler, M.V. Knopp, W.J. Lorenz

A.M.J. Paans, S.P. Tilkema, J. Pruim, G.M. Visser, Ph. E. Elsinga, A. van Waarde, M. Studeny and W. Vaalburg PET-Center, University Hospital, Groningen, The Netherlands.

Institut for Radiologie und Pathophysiologie Deutsches Krebsforschungszentrum, Heidelberg, FRG

PERFORMANCE PARAMETERS OF THE SIEMENS 951 ECAT POSITRON CAMERA ~ITH ITS NEW COMPUTER CONFIGURATION.

PHYSICAL ASPECTS OF QUANTITATION IN WHOLE-BODY PET The prerequisite for any biological or medical interpretation of PET images is the accurate and precise measurement and presentation of regional radioactivity concentrations in the imaged slices. The accuracy of this activity measurement is influenced by several factors, the following of which are of particular importance in whole-body PET: a) attenuation, b) scattering, c) count rate capability. Attenuation leads to very large correction factors on the order of 100. Scattered coincident radiation can not be corrected exactly. The maximum permissible coincidence count rate is highly dependent on the size of the object. Sensitivity is the main limiting factor in emission as well as in tranmission measurements. Also the non-uniformity of reconstructed images is dominated by statistics rather than by intrinsic factors of the tomographs. The physical background, the magnitude of effects, the possible corrections, and the limitations caused by these factors will be presented and discussed.

The performance of the Siemens 951 ECAT positron camera with the new advanced computer system (ACS) consisting of 2 rings of EGO block detectors with a total axial length of 10.8 cm will be discussed. Each detector block consists of 8*8 BG0 detectors, so in total 8192 detectors are employed. The data acquisition and reconstruction processes are coordinated by a SUN work station with its own disk space. Via an ethernet more workstations can he installed for image analysis. The operator workstation is interfaced via ethernet to the VME bus of the advanced computer system. The ACS consists of a Motorola 68020 processor, the real time sorter, extra memory and a 66 MFlops array processor for image reconstruction. The ACS has its own disk space available via a SCSI bus on the VME bus on which the sinograms are stored. The 68020 processor also controls the gantry and the motions of gantry and bed. The reconstructed images are stored on the disk of the operator SUN work station and for image archiving an erasable optical disk is available. The average spatial resolution amounted to 5.0, 5.1 and 4.8 mm FWHM in respectively the X-, Y- and z-direction in the center of the field of view. At a radius of i0 cm these numbers amounted to 5.6~ 5.2 and 5.5 mm FWHM respectively. The sensitivity as measured with a 20 cm diameter, 20 cm long phantom was 125,000 cps/pCi.mL. The count rate performance was measured up to a concentration of i0 ~Ci/mL. A scatter fraction of 12% was measured with a cold spot phantom. Figures on the speed of reconstruction and the speed of 3-D image formation~ based on the 31 2-D image planes will he presented.

PO-2R1-17

PO-2R1-18

MABD Plaizier 1, EB van Dieren 1, A van Lingen a, HJ Haisma 2, W den Hollander I, E Boven z, M R Bulst3, M van Loon 1, P

C SCH[18ER(,)/REGALL(-),P:SIFFERT(*,) and J.CHAMBRON(,) , Ins[itutde PhysiqueBiologique.(IPB) Foeul{~de !.~4decine.4 rue Kkschleger 67085 SlrosbourgCede× - Cenlrede RecherehesNucl#aires.(CRN) 6 rue du LoessStrasbourg-Cronenbourg. [ronce

Kenemans,3 OJJ Teule,1 JC Roos.i Deots of Nuclear Medicine,1

Medical Ontologyz and Gynaecology 3. "Free University Hospital, 1081 HV Amsterdam, The Netherlands. BONE MARROW DOSIMETRY FOR In-lll or 131-I LAB~.I.~D ANTIBODIES (MoAbs), BASED ON WHOLE BODY, BLOOD, AND IMMUNOSCINTIGRAPHIC DATA Bone marrow (bm) dosimetry is based on indirectly obtained data. Several approaches have been proposed, using one or more of the following sources: blood, bm, and remaining body. We compared 4 non-invasive methods after the diagnostic administration of 2 radiblabeled new MoAbs: Illln-OV-TL3F(ab)2 against ovarian cancer (150 MBq iv) and 1311-16.88 IgM against colon cancer (185 MBq iv). In contrast with 1311, a part of 1111n is trapped in the bin. Methods: 1.Based on repeated whole body measurements, the b m dose was calculated (MIRD) assuming homogeneous distribution of activity (bml). 2.This b m l value was corrected for contribution of the blood to the b m dose according to Bigler et_ al. (Proc. 4th Int Radiopharm Dos Syrup, Oak Ridge, 1986) assuming equal activity concentrations in blood and bm (bin2). 3.Bin activity was measured by repeated scintigrams in a small sacrum ROI, assuming 5 cm thickness and 67 "4o'1% bm and blood. The resulting dose was added to the bm dose from the remaining body (bin3). We developed a 4th method in which all 3 sources are implemented: whole body retention, early blood activity values, and T½ of sacrum activity (bin4). Results: (mean -+ sd): 1311-16.88 (18pts) 111In-OV-TL 3 (13pts) bml 0.14 -- 0.02 0.23 +_ 0.05 mGy/MBq bm2 0.43 _+ 0.17 0.30 + 0.05 " bm3 1.00 _+ 0.34 0.77 _+ 0.29 " bin4 0.46 _+ 0.26 0.83 _+ 0.39 " Concinsion: The combined use of T½ of bone marrow activity and whole body and blood activity values might be an appropria t e non-invasive approach to bone marrow dosimetry and useful for any radionuclide.

A MINIATURELOW-RESOLUTIONIMAGtNGDEVICEFOR CARDIACMONITORING AmbuMon/ monitoring of ven[riculor funcbon parameters together with ECG ~'f~ta could be helpful in the follow-up of patients with coronary disease. Non imaging probes using miniature Cadmium-Telturide (CdTe) have been used id the early 70's (Berger e[ al.) but encountered technical difficulties including an insufficient sensitivity (small odive area). Since, INa Coupled with miniature PM tube ( VEST, Capiniech Corp.), followed more recently by Cesium-Iodide/photo-diode (Cardioscint, Ookfield Inst.) monode~ectors have been developed and comercialised. The gated blood pool method at equilibrium was used (20 mci-g9mTc-RBC). Although sabsfaciory results have been obtained with such devices, we must agree with W.M.Sreisblatt who has summarized (JNM:52,44,1991) the characteristics of an ideal detector system: "we need on image to assess regional fund[on" and to control the geometry during the acquisition. procedure. The detector deportment of lhe CRN have a long experience with CdTe detedors nowadays, o new generation of detedars is available (lO, lOQmm).The NM dept. end the CRN have designed a 12 miniature detector system [hat gives r~o'~ reliable clinical results. At the present time the device is not yet autonomous end still too heavy (7DOg) to be portable. All clinical investigations have been made at the patient's bedside during one hour. The sensitivity of any element is sufficient to obtain d representative regional ventricular curve each 50 sec. with a temporal resolution of 50msec. The matrix non-uniformily is corrected. The posilionning algorithm consist of o. visual display of the detector counts o~ cyclic count-rate modulation The background is determined by using a detector outside the cardiac, area. Presenl development concerns the electronic miniaturization

603

Monday, 2 September 1991

PO-2R1-19

PO-2R1-20

A Skrettin~, R Plantener The Norwegian Radium Hospital, N-0310,Oslo 3

Z. S z a b o , C. S e k i , J. R h i n e , J. L i n k s , T.K. N a t a r a j a n , H.N. W a g n e r Jr., E.E. C a m a r g o . The Johns Hopkins Medical Institutions, Baltimore USA.

A ROTATING M U L T I P L E SLIT COLLIMATOR FOR THE S C I N T I L L A T I O N CAMERA: T E C H N I C A L S O L U T I O N AND INITIAL RESULTS.

A collimator, consisting of equidistant and parallel 1.5 m m t h i c k lead plates, spaced 5.5 mm apart, has been constructed and adapted to the camera by modifications of an ordinary Siemens collimator support. The collimator may be rotated in equal angular steps around the center of the scintillation camera crystal. A point source in front of the camera will create a line in the image, and sources along the same slit will contribute approximately additively to the integral of the image intensity in the image region corresponding to the actual slit. Thus, by rotating the collimator, approximate projections of the source distribution may be obtained for a large number of angles,and the image may be recontructed by means of slightly modified SPECT software. The implementation of the method was considerably facilitated by the use of an electronic circuit that performs a coordinate transform in such a way that the image y-axis always points in the direction of the slits. Thus, projections may be obtained by summing pixels along columns. Tests show that the sensitivity is increased by a factor of at least i0 compared to a general purpose parallel hole collimator, and that 99mTc test source configurations are still visible at a point in time when ordinar~ camera exposures with equal exposure time show nothing.

E F F E C T OF S P A T I A L R E S O L U T I O N O N A B S O L U T E QUANTIFICATION WITH HIGH RESOLUTION SPECT. A c c u r a c y of q u a n t i f i c a t i o n in S P E C T i m a g i n g is a f f e c t e d b y l i m i t a t i o n s in s p a t i a l resolution. T h e p u r p o s e of t h i s s t u d y w a s to investigate the p e r f o r m a n c e of a h i g h r e s o l u t i o n S P E C T s y s t e m ( N e u r o s p e c t 2000) a n d t h e e f f e c t of s e v e r a l v a r i a b l e s on q u a n t i t a t i v e S P E C T s u c h as: s p a t i a l r e s o l u t i o n a n d o b j e c t s i z e on t h e q u a n t i t a t i v e calibration; l e s i o n s i z e ( b o t h c o l d a n d h o t l e s i o n s ) on s c a t t e r a n d on r e c o v e r y c o e f f i c i e n t . L i n e a r s c a t t e r c o r r e c t i o n w a s a c h i e v e d for objects larger t h a n 18 mm. S p a t i a l r e s o l u t i o n w a s 4 . 7 m m F W H M in a i r a n d 5-8 m m F W H M in s c a t t e r m e d i u m . T h e c a l i b r a t i o n f a c t o r in CPM/~Ci was reproducible for o b j e c t s i z e s r a n g i n g f r o m 50 to 220 mm. R e c o v e r y c o e f f i c i e n t s as f u n c t i o n of l e s i o n s i z e a n d background a c t i v i t y w e r e f o u n d as f o l l o w s :

BG

(%)

9

0 50 100 150

.18 .37 .77 1.52

Lesion 22

15 .52 .60 .80 1.14

.95 .92 .92 .99

size 28

(mm) 34

56

.99 .94 .83 .92

i.i0 1.08 1.02 1.22

1.04 .91 .84 1.11

In c o n c l u s i o n , high resolution SPECT allows absolute quantification of r a d i o a c t i vity be

in l e s i o n s

adequate

for

over

20 m m

tracer

in s i z e ,

kinetic

which

PO-2R1-21

PO-2R1-22

H.Thierensl, A. Vral2, J.P.Van Haelst3,CNan de Wiele, K. Schelstraete3 and L. De Ridder2. 1) Medical Physics Laboratory, 2) Laboratory f o r Histology, 3) Dept of Radiotherapy and Nuclear Medecine University of Ghent, Belgium. DOSIMETRY AND RADIOTOXIClTY OF 9gmTc-HM-PAO IN HUMAN LYMPHOCYTES. In view of the r i s k f o r neoplastic transformation the i r r a d i a t i o n dose induced in human lymphocytes (LC) labeled with 99mTc-HM-PAO is of considerable i n t e r e s t . Due to the i n c e r t a i n t y on the dose contribution of low energy Auger electrons with ranges smaller than the cell diameter, calculated dose estimates are u n r e l i a b l e . We quantitated the dose and r a d i a t i o n - i n d u ced i n h i b i t i o n of the p r o l i f e r a t i v e capacity using the cytokinesis-blocking micronucleus assay. Isolated LC were incubated with varying a c t i v i t i e s of 99mTc-HM-PAO ranging from 10 to 900 MBq in a volume of 2 ml during 15 min. To evaluate the dose delivered to the c e l l s by e x t r a c e l l u l a r a c t i v i t y during the labeling procedure incubations with 99mTc04 were also carried out. In addition LC suspensions were i r r a d i a t e d in v i t r o with 250 kV X-rays to determine the dose response curves. A f t e r l a beling or external i r r a d i a t i o n , cultures were i n i t i a t e d with 5 106 LC using PHA as mitogen. The data reveal that i n t r a c e l l u l a r ggmTc is strongly r a d i o t o x i c , e v i d e n t l y due to important Auger electron groups. As indicated by the micronucleus frequencies the r a d i a t i o n burden of LC due to an i n t r a c e l l u l a r a c t i v i t y of 3.7 MBq/I07 c e l l s is equivalent to 5 Gy of X-rays. Compared to t h i s value the dose induced by e x t r a c e l l u l a r a c t i v i t y during the labeling procedure is completely neg l i g i b l e . I t appears that labeling of LC isolated from 46 ml blood with the usual a c t i v i t y of 925 MBq 99mTcHM-PAO results in an i r r a d i a t i o n dose of approximately 45 Gy (labeling e f f i c i e n c y 30 %). A f t e r t h i s dose LC cannot longer be stimulated to p r o l i f e r a t e . The same conclusion is also v a l i d when unseparated populations of leukocytes are labeled with s i m i l a r a c t i v i t i e s .

Thomson WH, Williams N~, Franklin N, Tulley NJ, Mills AP, Harding LK. Department of Physics and Nuclear Medicine, Dudley Road Hospital, Dudley Road, Birmingham B18 7QH, UK.

604

may

studies.

A PHANTOMFOR THE QUALITY ASSURANCE OF MULTI-HARMONIC ANALYSIS SOFTWARE. The importance of q u a l i t y control of nuclear medicine software has been increasingly recognised e.g. the work Of the European Cost-B2 project. We have previously described a phantom which tested single harmonic Fourier software f o r cardiac studies and using t h i s detected a serious e r r o r in the calculated phase image f o r one company's software. The phantom has been developed to include higher level harmonics. I t is based on three concentric c y l i n d r i c a l shapes which generate a dynamic image of sinusoids representing the f i r s t three Fourier harmonic components. Higher harmonic components cou]d be generated i f required. Within the one dynamic image sequence, the amplitude of each harmonic component varies from 0 to 100% and the phase from 0 to 360~, The multi-harmonic software of a number of computer systems has been checked. We have found one program which generates an unexpected 180° s h i f t in phase f o r a l l t h r e e harmonics. FADS software can also be assessed although the number of FADS components is important. Two FADS components are required to generate each harmonic. The phantom concept can be applied to generate any p a r t i c u l a r curve shape, e~g. t y p i c a l LV curves. Also, the phantom can be simulated by software and t h i s method w i l l be described. With increasing i n t e r e s t in the use of the FADS analysis, and in multi-harmonic analysis of cardiac studies, t h i s phantom should prove useful f o r the t e s t i n g and development of such software.

Monday, 2 September 1991 PO-2R1-23

PO-2R1-24

All Union Institute of Medical Instrumentation USSR Varin A, Vishneva G, Kalantarov K, Nemirovsky S. Physical modeling of cerebral

blood flow.

Cerebral blood flow determination by radionuclides is widespread both by multiprobe method of dynamic study or

SPECT visualisation

(static

study). Validity of this both techniques is greatly depending of

programmes of curves

treatment or

reconstruction programmes. Estimation realised

of

these

sical (hydrodynamic) giving

programmes

could be

or by mathematical modeling or by phyvery

modeling. The first way is

rough approximation, but second is

more close to the reality, but difficult to perform.

an attempt

We made

to realize

a physical

modeling of tissue perfusion. By using special rate

spongeous

configuration

homogenous

distribution

throughout of model. from

model

material and

tubes in

it was possible to immiof radioactivity

Clearance curves of Xe-133

obtained. There is good correlation

in curves depending of measured flow on input to model. Scientigraphic images of Xe-133 distribution on

model

and curves from R.O.I. also pre-

sented.

E. Vestergren, L. Jacobsson, S. Mattsson, J. Bjure, R. Sixt, and P. Uvebrant, Departments of Radiation Physics in G6teborg and Malm6, Department of Pediatric Clinical Physiology, G6teborg BIOKINETICS AND DOSIMETRY OF Tc-99m HM-PAO IN CHILDREN I n t r o d u c t i o n : Tc-99m HM-PAO is used for studying cerebral blood flow. The aim of this study is to investigate the biokinetics of this substance and to calculate absorbed doses in children. Material and methods: Biokinetic studies of Tc-99m HMPAO have been performed in eight children aged between 2 months and 18 years. Anterior and posterior gammacamera scans were made at approximately 1, 6 and 24 hours p.i. The activity in brain, liver, lungs, kidneys and intestines was quantified using the conjugate-view method. Urine was collected during 24 hours. Results: The uptake in the brain shows a strong agedependence with an uptake of about 20% (corrected for physical decay) for the patients younger than 1,5 year, and 6 % for the 18 year old patient. The liver-uptake varied between 15 and 27%. The uptake in the lungs was 7,7 % (5,9-9,3%) and in the kidneys 5,7 % (3,5-7,1%). Between 0 and 6 hours the biological half-lifes in lungs, liver and kidneys were about 10 h, and between 6 and 24 hours about 50 h. The urinary excretion during 24 hours was 30 % (range 26-54%) The activity in the intestines at 24 hours was 15 % (8-21%). Conclusion: The uptake of Tc-99m HM-PAO in brain and liver is age-dependent. The young children have much higher uptake-values than those reported for adults. Data on absorbed dose to various organs as well as mean absorbed dose to the whole body and the effective dose will be presented.

PO-2R1-25

PO-2R1-26

B. Cleynhens, H. Vanbilloen, M. Hoogmartens, M. De Roo, A. Verbruggen. Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium.

D. Crombez, B. Cleynhens, G. Bormans,.M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

LABELLING CHARACTERISTICS AND BIOLOGICAL BEHAVIOUR OF GEM-DIMETHYL DERIVATIVES OF 99~Tc-

COMPARISON OF THE TECHNETIUM-CHELATING STRENGTH OF DIFFERENT TETRALIGAND SYSTEMS

MAG3

Labelling of C-methyl derivatives of MAG3 with 99mTc yields a mixture of 2 diastereomers. Compared to 99mTc-MAG3 [I, A = B = D = E = C H 2 ] a few of these isomers show superior renal excretion characteristics in humans, but their preparation requires an HPLC-purification step. To avoid the problem of isomer formation and isolation, we have now studied gem-dimethyl derivatives of I, beating a dimethylmethylene [-C(CH3)2-] instead of a methylene (-CH2-) in position A(H), _B(m), _D_D(IV)or _E(V). TcO [ S-_A-CO-N-_B-CO-N-D_-CO-N-_E-COOH] The S-benzyl protected precursors were synthesized by standard methods of peptide chemistry starting from aminoisobutyric acid. Their identity was confirmed by NMR. Reaction products after exchange labelling with 99mTcin the presence of stannous tartrate were analyzed by RP-I-IPLC on Hypersil ODS and contained mainly one radiocbemical species. This was isolated and its biodistribution was studied in mice (n=5) at 10 min and 30 rain p.i. All new compounds are efficiently cleared from the blood and their retention in the kidneys is low. Urinary excretion is rapid for HI and IV, although slightly lower than for I, and slow and incomplete for lI and IV, which show pronounced activity in liver and intestines. This indicates that substitution of I on a methylene in the mercaptoacetyl or terminal glycyl moiety alters the biological properties to the highest degree. Within the new derivatives HI shows the most optimal renal excretion characteristics and it will be further studied in other animal species.

Technetium-99m forms stable complexes with a variety of tetradentate ligands such as N,N'-bis(mercaptoacetyl)propanoate (CO2DADS), mercaptoacetyltriglycine (MAG3) , ethylenedicysteine (EC), ethylenedicysteine-diethylester (ECD) and tetraglycine (G4). In order to compare the chelating strength of these ligands we have labelled equimolecular amounts of each combination of two of these ligands with technetium-99m. Labelling was accomplished in 3 different conditions: exchange labelling (100°C-10 ') in the presence of 100#g SnCI2 + 15 mg tartaric acid at pH 5 and pH 8 and direct labelling at pH 12 (ligand + SnC12 + TcO4-) at room temperature. Direct labelling reaction mixtures were boiled for 10 min after the first analysis and then reanalyzed. Gradient RP-HPLC was used to determine the relative amount of the formed complexes in the labelling reaction mixtures. On basis of the results the examined ligands can be ranked in order of their chelating strength as follows: ECD > EC > MAG3 > CO2DADS > G4. The ranking is identical at each studied pH, except for EC that exhibits stronger chelating properties as compared to ECD at pH 12 but not at pH 5 and 8. The heating step resulted in an increase in the relative amount of the 99mTc-complex that was preferentially formed at room temperature. However, heating of the reaction mixture with G4 and CO2DADS after direct labelling at pH 12 resulted in an exchange of technetium from its initial G4 complex to the 99mTc-CO2DADS complex. It is concluded that the diaminodithiol tetraligand system binds technetium more firmly than the other examined tetraligand structures.

605

Monday, 2 September 1991

PO-RR1-27

PO-2R1-28

G. Demonceau, P. Bourgeois, J. Plum, J. C. Depresseux, E. D'Hondt, J.Boie, B. Thierens, A. de Schryver. St Elisabeth, Zottegem; Bracops, Brussels; U n i v e r s i t y of G e n t and Liege. (Belgium) V A L I D A T I O N OF L Y M P H O C Y T E S L A B E L I N G W I T H T C - 9 9 M HM-PAO. W e t r i e d to e v a l u a t e the f e a s i b i l i t y of i n j e c t i n g Tc-99m-HM-PAO-labeled lymphocytes to humans, u s i n g c e l l s that h a d b e e n e x p o s e d to r a d i a t i o n doses sufficient to fully inhibit their multiplication (and, thus, a v o i d i n g r i s k of t e r a t o g e n i c i t y ) , but not l a r g e e n o u g h to induce lethal d a m a g e L y m p h o c y t e s i s o l a t i o n w a s m a d e by the g r a d i e n t c e n t r i f u g a t i o n m e t h o d and p l a t e l e t s a g g r e g a t i o n w i t h A D P and A d r e n a l i n e . I n c u b a t i o n w a s m a d e w i t h 2.2 G B q of T C - 9 9 m - H M - P A O in a v o l u m e of 3 ml d u r i n g 1 hour. The a b i l i t y of the l a b e l e d cells to m u l t i p l y u p to 3 days a f t e r p l a s m a i n c u b a t i o n was e v a l u a t e d in v i t r o w i t h and w i t h o u t u s i n g 2 mg/ ml phytoagglutinin. The residual platelet a g g r e g a b i l i t y of the i n j e c t e d s u s p e n s i o n was also checked. Finally, after animal studies, b i o d i s t r i b u t i o n in 3 p a t i e n t s w a s e v a l u a t e d 2, 4 and 18 h o u r s a f t e r i n j e c t i o n of 300 M B q of l a b e l e d a u t o l o g o u s lymphocytes. The final suspension contained about 85% l y m p h o c y t e s , 13% p l a t e l e t s and 2% n e u t r o p h i l s . T h e l a b e l i n g e f f i c i e n c y w a s 31.3 ± 8.5%. T h e cell m i c r o d o s i m e t r y w a s e s t i m a t e d a b o v e i000 CGy. T r y p a n b l u e s t a i n i n g s h o w e d less t h a n 1% d e a d c e l l s a f t e r labeling. N o r e s i d u a l a g g r e g a b i l i t y and no cell m u l t i p l i c a t i o n was o b s e r v e d in vitro. No t o x i c i t y in t h e animal w a s observed. In all 3 patients, t h e b i o d i s t r i b u t i o n s t u d y s h o w e d low u p t a k e in the lungs, h i g h (2.1) s p l e e n / l i v e r r a t i o and h o m o g e n e o u s d i s t r i b u t i o n in the b o n e marrow. Clinical parameters were unchanged during the w h o l e study. We d e m o n s t r a t e d the f e a s i b i l i t y of the method, b u t the c l i n i c a l u t i l i t y of this t r a c e r in v a r i o u s p a t h o l o g i e s m u s t still be e v a l u a t e d .

D. Nosco, B. Weber, R. Rajagopalan, A. Verbruggen, G. Bormans. Hallinekrodt Medical, Inc. St. Lpuis, NO and University Hospital Gasthuisberg, B-3000 Leoven, Belguim. 99m-To COMPLEXES OF N3S LIGANDS; LABELING AND BIODISTRIBUTION PROPERTIES AND COMPARISON TO OIH. A number of N3S ligands of the general formula I have been prepared, and their labeling with Tc-99m attempted. Contrary to an earlier report (Schnelderp et al. 8th Int. Symp. on Radiopharm. Chem. Abst., p. 33; 1990), most do not form complexes with Tc-99m, even upon deprotection of the thiolato moiety and even upon application of a variety of labeling techniques. The two ligands that do form stable 99m-Tc complexes (n=2,m=l,q=l(~P 742) and n=l,m=2,q=l (HP 744) H 0 also were eomplexed to 99-Tc N-(CH 2 )mCNH and the 99-Tc samples were o=c I characterized by FAB-mass spee and (Cn2)~ (CH2)q UV/Vis. The 99m-Tc complexes of [ O=C MP 742 and MP 744 were evaluated S NH in rats,mice,rabbits and baboons. O=CC6H s CH2CO2H Biodistribution data are given I below for the mice and rats with the data compared to that for 131-1-o-iodohippurate (OIH):

742

Organ Ur+BI Kd Bld

Mice(30 min p.i.) %Te-99m %1-131 53 73 17 2.9 2.0 4.5

Rats(60 min p.i.) %Tc-99m %1-131 78 79 0.38 --0.07 ---

Ur+BI 64 78 72 79 Kd 21 4.9 0.22 --Bid 1.6 3.0 0.06 --These two complexes were evaluated in baboons with the clearances,as a percentage of that for 131-10IH, being 40 and 27, respectively. These results indicate that Tc-99m- labelled MP 742 and HP 744 may provide useful replacements for OIH in renal function studies. 744

PO-2R1-29

PO-2R1-30

H__=.E ~ s e n h u t , W.D. Lehmann ~ . R a d i o i o g i s c h e Kiinik, U n i v e r s i E ~ Heideiberg and * D e u t s c b e s K r e b s f o r s c h u n g s z e n t r u m , D-6900 Heidelberg, FRG.

G. Reidel and M. T. Ercan Isotopenlabor, Institut f{~r Strahlenbiologie, GSF, D-8042 Neuherberg, Germany and Department of Nuclear Medicine, Hacettepe University, 06100 Ankara, T~rkiye

MASS S P E C T R O M E T R Y OF B A T - C O N J U G A T E D ANTIBODY AHD I D E N T I F I C A T I O N OF A S U R P R I S I N G SIDE P R O D U C T A S S O C I A T E D W I T H N H S - B A T - E S T E R CONJUGATION

COUPLING OF 125I-EGF TO SERU~ ALBUMIN TO STABILIZE THE RABIOIODINE BOND Rapid in vivo deiodination of IL~I labeled epidermal growth factor (EGF) was a major disadvantage in studies t.o localize EGF receptors in tumor implanted nude mice. The present investigation was ur~ertaken to stabilize the radioiodine bond by coupling EGF to mouse albumin by the cyanuric chloride method. For labelling 17 ~l EGF solution (33 ~g=5.17 nmol)

N - H y d r o x y s u c c i n i m i d e (NHS) is an o f t e n u s e d leaving g r o u p for the c o n j u g a t i o n of radioactive labels or c h e l a t e s w i t h m o n o c l o n a l antibodies. A c c o r d i n g l y , the first N H S - B A T ester (BAT = b i s { a m i n o e t h a n e t h i o l ) ) , recenEiy d e v e l o p e d bY our laboratory, conjug a < e d r a p i d l y w i t h lysyl groups of IgG or f r a g m e n t s aE pH 8-8.5. The c o n j u g a t i o n y i e l d r a n g e d b e t w e e n 50-60%. U V - l a s e r d e s o r p t i o n / i o n i s a t i o n - m a s s s p e c t r o m e t r y of the B A T - c o n j u g a t e d IgG r e v e a l e d an i n c r e a s e in mass w h i c h was in a c c o r d a n c e with the amount of B A T - l i g a n d s b o u n d m e a s u r e d by photometry. Under these c o n d i t i o n s we aliways d e t e c t e d a side product in 40-50% y i e l d w h i c h was not a s s o c i a t e d wi~h or b o u n d to the prorein. HPLC a n a l y s i s e x c l u d e d the h y d r o l y t i c c l e a v a g e of the NHS group. Therefore, at first we i n t e r p r e t e d its a p p e a r a n c e with an inrra-or i n t e r - m o l e c u l a r reaction, since the N H S - B A T ester c o m p r i s e s n u c l e o p h i l i c centers. However, F A B - m a s s s p e c t r o m e t r y of this c o m p o u n d s u r p r i s i n g l y p r o v e d a mass of M+IS, i n d i c a t i n g N H S - r i n g opening. This f i n d i n g has c o n s e q u e n c e s for the kit devel o p m e n t u s i n g ~9~Tc c o m p l e x e d N H S - B A T esters in the p r e c o m p l e x a t i o n route.

606

was placed in an iodogen cup. 50 ~tl 0.5 M phosphate buffer (pH=7.5) and 4 ~l 125I (74 MBq) were added in succession. After 2 rain 125I-EGF was obtained with an efficiency of ~ 90 %. For coupling,2 ~l (2 ~g=10.8 nmol) cyanuric chloride was added and left to react for 2 rain. 10 pl mouse albtuain (660 pg=10.2 r,~ol) was added and after 30 min the reaction mixture (83 ~l) was injected to an HPLC column (Superose 12, 300x10 ram, Pharmacia-LKB) and eluted with 0.05 M phosphate buffer (pH=7.0, 0.5 ml/min, UV:254 rim). 0.5 ml fractions were collected and counted in a dose calibrator. Albumin coupled EGF was obtained in an overall efficiency of ~ 30 %. There was < 1 % l~Ifor both '125I-EGF and 125I-EGF-AIb, determined by ITLC-SG strips and saline as a solvent. The biedistribution in NMRI mice showed that the liver and blood radioactivity levels were higher with 125IEGF-Alb compared to I~I-EGF with TIP2 for whole body retentions being i4 and 1.5 h, respectively. The higher retention of coupled EGF might increase its tumoral uptake in nude mice. Further studies are warranted to demonstrate its efficacy.

Monday, 2 September 1991

PO-2R1-32

PO-2R1-31 T. Forster, By. SGskuthy,

P. Kom~romy

Biomedical Oiagnostics Laboratories Institute of Isotopes P.O.Box 77, H-1525 Budapest, Hungary

M.J. Kelly r A. Cowie, A. Antonino, V.Kalff, H. Barton*. Nuclear Medicine Department, Alfred Hospital, Melbourne, AUSTRALIA. OPTIMISING MDDIFI~

METHOD FOR TESTING OF 99mTc CHELATING PROPERTIES OF BIOTIN-DERIVATIVES

ANO OTHER CHELATORS

We have synthesized several biotin-derivatives for indirect labelling of MoAb-s using the biotin-avidin system. These biotin-derivatives chelate 99mTc strongly and retain their affinity to avidin. These ~re planned to be used as a component of a kit. Besides this main application we have used these compounds for testing of the 99m-To chelating properties of these and other chelators. Each biotin-derivative was labelled together with EDTA as a competitive reference-chelator. Complexes formed by EOTA and biotin-derivatives w e r e separated using avidin and ultrafiltration. The specific and very strong binding between avidin and 99m-Tc labelled biotin-derivatives makes it possible, to separate these from 99m-To labelled EOTA without destroying the structure of the eompiexes. The distribution of radioactivity between the biotin-derivatives and EDTA in differen~ points of time gives information about the chelating properties of the biotin-derivatives compared to EDTA. Using a biotin-derivative as a competitive r e terence-chelator it is possible to test any other chelator on a relative scale. Chelating properties of EDTA, DTPA and tartaric acid w e r e tested using N-biotinil-3,5 di((N,N-bisoarbo×ymethyl) aminemethane) tyramine as a competitive chelator.

PO-2R1-34

PO-2R1-33 KGrnyei~

J.

I N - V I ~ O I~nRT.T.7~G O F ERYTHROC"flT~

Modified in-vivo labelling of er/dlrocytes with Tc-99m has on sc~e occasions given clinically suboptimal results in this laboratory. ~hese w e r e characterised b[ >>10% of the Tc-99m remaining unbound (%FREE) at the tlme of reinjection. In order to fully optimise the labelling technique the following factors which could contribute to clinically unacceptably high %FREE were assessed: A) Time from administration of tin (I rag) to ~ of incubation of blood with Tc-99m (TIN TIME); B) Volume of blood withdrawn to incubate with Tc-99m (BL. VOL); C) Incubation time of blood with Tc-99m (INCUB TIME); D) Time delay between the last two successive generator elutions (G~q ~ ) . In assessing each factor duplicate labelling of blood specimens with 800MBq Tc-99m (mean TcO4-vol. 0.6ml, range 0.2-1.5mi) using 5ml syringes in Tungsten shields, was performed on i0 patients without recent transfusion. Approx. 0.2-0.4ml of heparinised saline (i0 units/ml) was added to each ~ubale. %FREE (mean +S~) was calculated following tion on a rotating inverter and separation in a centrifuge. %FREE results are ~ i s e d as follows: (A) T I N T I M E (rains) (B) BL VOL (ml) 5 i0 15 20 30 i. 5 3.0 %FREE 19+--2,*12+_2 10+-2 11+-2 12+-2 22+--4*** i0+i (C) ~B T ~ E (mins) (D) ~ REG~Wm i0 20 30 >48hrs <24hrs %FREE 19+3,** 12+2, 11+2 ~3+5,** --13+2 (* = P<0.O5, ** = P<0.01, * * * = P < 0 . 0 0 1 v s g r o u p low) This assessment showed optimal labelling of erythrocytes is achieved when T/~ TIME is _>i0 rain, BI. Vol >3 mls, INCUB TIME >20 rain and of critical i n , p o n c e is double elution-if G ~ REGROWI~ is >24hrs.

, Szilv~ei,

I.~ T~rkG,

J.

Institute of Isotopes of the Hungarian Academy o~ Sciences, H-1525 Budapest, POe. 77 -Postgraduate Medical Seool, Budapest,HUNGARY Tc-99m -EC AS POTENTIAL KIDNEY AGENT Sulfur containing molecules like HAG-5, Arabinoso-tiazolidin and EC (N,N'-ethylen-dicystein) a r e recently investigated in our laboratory. Normal kit formulation was elaborated except EC where a special condition, i.e. strong alcaline medium (pH=I2) was required for obtaining pure Tc-99m complex. Radiochemical purity measurements were carried Out on reverse phase TLC (RP-18 layer). Biodistribution studies were done on rats and rabbits. AI1 compounds are taken up by the kidEC showed the fastneys. Among them, T c - 9 9 m est kidney uptake and has the best tubular excretion properties, with T(max) = 5.8 + 0.Smin. and T(1/2) = 8,5 + i min. Plasma binding properties of HAG-3 and EC showed that the data of the latter one (28 %) is very similar to the iodo-hippuran (35 %). Tc-99m EC seems to be an excellent tubular kidney agent and our special termuiated kit is under registration procedure in Hungary.

P.Kom~rek ~ M.Konopkov~ J.Kidery ~Postgraduate Medical and Pharmaceutical Institute; Institute for ClinicaI and Experimental Medicine, Prague, Czechoslovakia LABELLING AND BIOLOGICAL EVALUATION TISSUE PLASMINOGEN ACTIVATOR

OF 99mTc-

Tissue plasminogen activator (t-PA) is suitable for thrombolytic therapy. Using technetium (99mTc), we study localization of thrombi and damaged vessel walls. The aim of our study was labelling of t-PA with 99mTc and biological evaIuation of this potential radiopharmaceutical. t-PA was labelled with sodium pertechnetate (99mTc) using stannous chloride as a r e ductant The labelling efficiency and radiochemical purity of 99mTc-tPA were evaluated by means of paper chromatography, electrophoresis and membrane filtration. The highest labelling efficiency was 98 %. To obtain information on 99mTc-tPA accumulation in malignant lesions, experimental rats with implanted Walker-type tumours were used. The tumours were imaged on days 4 through 14 since implantation during which period scintigraphic images showing good accumulation of labelled t-PA in tumours were obtained at 4, 6, 24 and &8 hours after i.v. administration of 99mTc-tPA. According to age of tumours, the activity of 99mTc increased from i % to lO % per whole tumeur and was 0.10.2 % per g of tissue of the same tumour. This may be the first report of t-PA labelling with 99mTe. Because of the excellent physical properties of ??mTc, this radiopharmaceutical can be considered potentially useful for thrombus detection as well as for early tumour localization

607

Monday, 2 S e p t e m b e r 1991

PO-2R1-35

PO-2R1-36

K.-H. M a t z k e , G.-J. M e y e r , A. S c h i m k e , H. H u n deshagen, Abteilung Nuklearmedizin und spezielle Biophysik, Medizinische Hochsehule H a n n o v e r , D - 3 0 0 0 H a n n o v e r 61, G e r m a n y

J.Mertens, M.Thomas, I.Zolle , P.Angelberger VUB-Cyclotron, B-I090 Brussel, ~Nucl. M a d . 2 n d Medical Clinic, A-1090 Wien, *~Forschungszentrum Seibersdorf, Austria

An AUTOMATED SYSTEM FOR THE APPLICATION OF 15e-WATER AS A BOLUS, A CONSTANT-, OR A RA~IP-/NFUSION.

RADIOSYNTHESIS OF ANALOGUE FOR SPECT

!50-water is the most widely used marker for the investigation of cerebral blood flow, cerebral oxygen util%zation, and extravascular water. Depending upon the clinical question, it may be administered by different protocols, such as bolos injection of up to 3.7 GBq, steady state infusion in the range of 50 - 300 Y~q/Min, or ramp infusion with increasing or decreasing specific activity. Especially frequent and repeated application of the bolus will results in s high radiation dose to the personnel, so that this process should be widely astomated~ For this reason we improved our previous constant infusion system (Meyer et al ill). 150 is produced by the 14N(d,n)lS0 reaction in a nitrogen gas target containing 0.5% oxygen as carrier. The 150-water system is in a distance of about 50 m from the cyclotron, right beside the PET camera. It is shielded by a lead box {20x30x20 cm, wall thickness 5 om} mounted On a laboratory trolley. In the lead box the target gas is mixed with hydrogen,and passed through a tube oven, filled with appr. 0,2g Pd (1%) catalyst on carbon. Reaction temperature is 150°C. The 150-water vapour is trapped in a 4 necked flask, filled with is0tonlc saline solution. The level of the aa!ir~.e in the flask is monitored continuously by a set of 10 light barriers. This level control unit commands a gear pump outside the lead box, which withdraws physiol. NaCl from an infusion bottle. With a second small gear pump, the 150-water is pumped out~ via a calibration detector and a sterilization filter. In case of c0nstant infusion or ramp iejeeti0n, this follows instructions of the level control unit. In case of a bolus injection, the labelled water is pumped as fast as possible into a pneumatic driven syringe~ placed in a dose ealibrator, from where it is injected at a predefined dose level. I} G.-J. Meyer,et al. J. labelledC0~tlp.Radiopharm.2~,!209-1210 {1986)

PO-2R1-37 A Moisan, B Collet, S Mares, A Devillers, J Le Cloirec, PL Etienne, JC Saccavini and P Bourguet Centre Eugene Marquis, Rennes - ORIS, Saclay - France In 111 Feb'2 NCA 102 : A NEW ANTIGRANULOCYTE ANTIBODY TO IMAGE INFECTION. NCA 102 is a new IgG1 antibody directed against the NCA 95 protein, a granulocyte celt surface component. Feb'2 fragments were produced and labelled with DTPA In 111. Cytofluorometry studies showed that this IgG1 antibody bound to 97,5 % granulocytes but not to red blood cells (0,1%) or lymphocytes (0,2 %), Scatchard analysis gave a binding constant of 1.1 t09 l/mole for intact antibody and 1.9 108 I/mole for the Fab'2. Two hundred and fifty micrograms of Fab'2 fragment labelled with 15 MBq In 111 were injected I.V.. Five patients were imaged at 3 hours and 24 hours. In 111 scans were compared 24 hours later to Tc9gm HMPAO leukocyte scintigrams performed 3 hours post-injection. Mean blood radioactivity was estimated 28 % at 3 hours and 8 % at 24 hours post-injection, the activity bound to granulocytes averaged 35 %, For these patients, 10 % of the injected dose was excreted in urine within the first 24 hours. Infection loci were localized in all cases with both procedures. The In TM Fab'2 NCA 102 antibody therefore seems interesting in the immunoscintigraphic detection of sepsis.

608

A

POTENTIAL

METYRAPONE

2'-Br-2-methyl-2-(3-pyridinyl)propiophenone l, a new A-phenyl Metyrapone analogue, shows the highest llS-hydroxylase inhibition a c t i v i t y as c o m p a r e d to e a r l i e r d e v e l o p e d analogues (Zolle e t al. 1 9 9 1 ) . T h e s l i g h t i n c r e a s e of l i p o p h i licity observed when exchanging the bromo for iodine on the 2'-position lead to suppose that 2'-12aI-2-methyl-2-(3-pyridinyl)propiophenone s h o u l d i. s h o w a c o m p a r a b l e a c t i v i t y a n d ii. b e a potential tracer for SPECT. NCA labelling is a c h i e v e d b y C u +I a s s i s t e d n o n - i s o t o p i c exchange in r e d u c i n g conditions: 0 . 5 m g of l, 5 m g of gentisic a c i d , 7 m g of c i t r i c a c i d , 0 . 2 m g of S n S O 4 a n d 5 x i0 -~ m o l C u S O 4 a r e h e a t e d in 5 0 0 p l of ~0% M O A c d u r i n g 40 m i n u t e s (Mertens et al. 1 9 8 7 ) . W i t h a s u b s t r a t e / C u +I r a t i o of 4 . 4 a labelling y i e l d of a b o u t 9 5 % is o b t a i n e d . NCA is o b t a i n e d by semi-prep HPLC separation on a Lichrocart 250 x i0 m m l0 p R P S e l e c t B column (MeOH/ACN/H20//TMA/HOAc : 25/16/ 58//0.4 /0.6 brought to pH 7.4 with NaOH)" and by appropriate mini-column preconcentration and rec o v e r y in e t h a n o l . A f t e r a d d i t i o n of i s o t o n i c saline and sterilization the radiopharmaceut i c a l is r e a d y f o r in v i v o use. References Mertens, J., V a n r y c k e g h e m , W., G y s e m a n s , M., E e r s e l s , J., F i n d a - P a n e k , E.j a n d C a r l s e n , L,. Eur. J. N u c l , M a d . 13, 3 8 0 - 3 8 1 , (1987). Zolle, I., Yu, J., Robien, W., et a l . . J. Labelled Compd, & Radiopharm. XXIX(3~, (1991).

PO-2R1-38 Gil!ian F. Morgan, Marcel Deblaton, Paul Van den Broeck, 8enoit 8astin~ Robert Pirotte, Philippe Michel, Pierre Clemens, Ulrich Abram and John R. Thornback. MEDGENIX Diagnostics and LR.E~ 5220 F]eurus, Belgium and ZFK, Postfach 19, O-8051 Dresden F.R.G. BIOLOGICAL STUDIES OF NEUTRAL TECHNETIUM (V) COMPLEXES CONTAINING NNOS DONOR SETS. A series of ligands was designed and synthesised by Medgenix which upon coordination with technetium yield neutral and lipophilic complexes capable of crossing the blood brain barrier. We recently reported Phase I clinical resutts of one of these, MRP20 (1), N-2-1H pyroiytmethyFN'-4pentene-3-one-2-ethane-l,2-diamine. As part of the development we tested two tigands (MRP40 and MRP41 ) where the coordinating pyrrole group is replaced by a reactive thiol, known to have strong complexing affinity to technetium. The complexes form by heating the thiol-protected ligand with [99mTc| pertechnetate and stannous chloride in an ethanoVsaline mixture at I00°C for 10 mine, Animal biodtstribution studies were performed on female Winter rats using a preparation which had been purified by HPLC. Brain uptake at 2 min.p.i, was 1.1%(MRP40) and 1,2% (MRP41) i.d.. At 3h pJ., the brain uptake was still significant, t.02°,'o (MRP40) and 0.69% (MRP41) Ld.. Blood activity levels were very high, w~h 63.9% (MRP40) and 40,3% (MRP41) i,d. at 2rain. pJ. falling very slowly to 17.4% (MRP40) and 7,12% (MRP41) after 3h. tn vitro blood labellingstudies showed between 60 and 70% of this activity is associated with the blood cells, Characterlsation of the injected complex was achieved bY eoinjection on HPLC of the carrier and no-carrier added technetium complexes. Synthesis of the 99Tc compound of t-~vlRP40 was effected using the reactive precureer, [TcOCI4]'. The compound was fully charactedsed by nmr, mass spectroscopy and a single crystal X-ray study as TcO(MRP40)o Coinjection of a mixture of the99mTc and 99Tc complexes gave identical elufion times for the compounds which was verified using two HPLC solvent systems, These studies contribute to our increasing knowledge of the biologicalbehavtour of the MRP Ilgand series (2). The brain uptake observed in this study indicates that the trapping mechanism for MRP20 is not dependant upon the pyrotle group. (1)Bossuyt et aL Nuclear Medicine, Schattauer (1990) p222~224. (2) Morgan et al lbid (1990) 115-117

Monday, 2 September 1991 PO-2R1-39

PO-2R1-40

~:_~_~2~, Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge, U.K.

H.J.Steinmetz and K.Schwochau, I n s t i t u t ffir C h e m i c 1 ( N u k l e a r c h e m i e ) , F o r s c h u n g s z e n t r u m Jfilich G m b H (KFA), D - 5 1 7 0 Jfilich, F.R.G.

Tc-99m EXAMETAZIME-LABELLED LEUCOCYTES: EFFECT OF CONCENTRATION AND VOLUME OF LIGAND ON LABELLING EFFICIENCY. The recommended method for labelling Leucocytes with Tc-99m exametazime is to incubate the cells with 4 mls ligand containing 400 ~g exametazime. However, a labelling efficiency (L~) of only 27-55% is achieved. We have investigated the effect of concentration and volume of exametazime in an effort to improve the LE. A vial of exametazime (500 wg) was made up to 4 mts with saline. Aliquots of 0.25 ml to 2.0 ml were removed, added to pertechnetate (1000 MBq) and incubated with 3x107-8x107 leucocytes from 25 mls fresh venous blood. The LE was determined. In a sgcond study a vial of exametazime was made up to 1.5 mls with saline i.e. a concentratiod of 333 ~g/ml. Aliquots of 25 ~g to 200 ~g were removed, made up to 0.6 ml, added to pertechnetate and incubated with'{he cells as before. The results show that the LE decreased as the volume of Ligand increased. Thus for 0.25 ml the LE was 65%±6 SD and for 2.0 ~l the LE was 45%~8, n=4. Also, the LE decreased as the concentration decreased. For 200pg/ 0.6 ml the LE was 66%~4 and for 25yg/0.6 mL the LE was 53%~10. Having established that a high concentration and low volume gave the highest LE clinical studies were performed using 50 mL patients' blood and a concentra~on of 200 ~g/0.6 ml of Tc-99m exametazime. The LE was 82%±7. We conclude that high labelling efficiences can be achieved using a high concentration and low volume of Tc-99m exametazime.

PREPARATION, ISOLATION AND CHARACTERIZATION OF TECHNETIUM COMPLEXES CONTAINING s-AMINE OXIME SUGARS

~s an extension of o u r i n v e s t i g a t i o n s on 9 T c / 9 9 m T c c o m p l e x e s for m y o c a r d i a l and b r a i n perfusion imaging, we began to s t u d y t h e c o o r d i n a t i o n c h e m i s t r y a n d b i o d i s t r i b u t i o n of Tc complexes containing a-amine oxime sugars. The bifunctional ligands Dg l u c o s a m i n e oxime, D - m a n n o s a m i n e o x i m e a n d Dgalactosamine oxime we e synthesized and c h a r a c t e r i z e d . The n e w 9~Tc c o m p l e x e s , f o r m e d b y r e d u c t i o n of p e r t e c h n e t a t e w i t h d i t h i o n i t e in e x c e s s of the ligands, w e r e p u r i f i e d b y anion exchange and solvent extraction, separated by HPLC and characterized by elemental analysis, UV/VIS/IR spectroscopy and capillary electrophoresis. The brown compounds proved to b e k i n e t i c a l l y rather s t a b l e in a q u e o u s s o l u t i o n s . T h e y a p p e a r to contain three s-amine oxime sugar molecules c h e l a t i n g Tc t h r o u g h the n i t r o g e n atoms. T h e structures are stabilized by molecular hydrogen bonds between oxime and oximate g r o u p s of t h e c o o r d i n a t e d ligands. T h e IR s p e c t r a i n d i c a t e the a b s e n c e of T c = O bonds. Parallel to more detailed structure i n v e s t i g a t i o n s w e a r e c u r r e n t l y m e a s u r i n g the biodistribution of the ~ m T c complexes in mice.

PO-2R1-41

PO-2R1-42

K. Verbeke, C Van Nerom, G. Bormans, H. Vanbilloen, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

Zei-Tsen Tsai'" " Institue of Nuclear Science,National

PITFALLS DURING LABELLING OF A FIBRIN-SPECIFIC MONOCLONAL ANTIBODY WITH TECHNETIUM-99m Efficient and practical methods for direct labelling of antibodies (Ab) with 99mTc rely on initial cleavage of disulfide bonds in the Ab to free thiols by a mild reducing agent (RA), followed by the addition of a weak 99mTc-chelate. RA's most commonly used are mercaptoethanol (ME) and dithiothreitol (DTT). We have used such methods for 99roTe labelling of MA-15C5, a routine monoclonal antibody (MAb) directed against a neoantigenetic determinant which is only expressed in fragment D-dimer of human cross-linked fibrin. MA-15C5 was a gift of the Centre for Thrombosis and Vascular Research, K.U.Leuven. 99,el'c-labelled MA-15C5 would have potential as tracer agent for thrombus imaging in view of the high affinity of this MAb for fibrin. In our hands, however, none of the currently applied methods using ME or DTT in different conditions resulted in an acceptable labelling with preservation of immunoreactivity. Analysis by SDSelectrophoresis and size exclusion HPLC (SEC) revealed that the radionuclide was mainly bound to a fragment with low MW (about 25,000), possibly formed by dissociation of the light and heavy chains. This indicates that this particular Ab is affected by ME and DDT more drastically than most other antibodies. Successful labelling of MA-15C5 could however be attained using as reducing agent 2-mercaptoethylamine (MEA) in a molar ratio MEA:MAb = 1000:1. After incubation at room temperature for 30 rain, direct labelling was possible by the simple addition of 20#g SnCI2.2H20 and pertechnetate. On SEC-HPLC the 99raTe-labelled MAb showed the same retention time as the native MAb, which indicates preservation of molecular size. It is concluded that 2-mercaptoethylamine is a valuable additional reducing agent for labelling antibodies efficiently with 99raTc, It involves a lower risk for dissociation of the chains and impairment of the immunological properties than ME and DTT.

Ai-Yih Wan~*, Jiunn-Liang Lin", Jiunn-Guang Lo"

University " ' I n s t i t u e of Nuclear Energy Research CHEMICAL B E H A V IOR

CHARAC'I~IZATION OF PERTCHNETATE

Tsing Hua

OF COHPLEXATION WITH C Y S T E INE

T h e l a b e l l i n g o f c y s t e i n e w i t h "'Tc04- a n d /or "9~Tc04- in d i f f e r e n t I igand c o n c e n t r a tion , reductant and pH value was described in t h l s p a p e r . T h r e e d i f f e r e n t m a j o r T C - c o m p l e x e s w e r e s e p a r a t e d b y gel p e r m e a t i o n c h r o m a t o g r a p h y (GPC). T h e c h a r a c t e r i s t i c a b s o r p tion maxima of Tc-complexes in t h e v i s i b l e range of the spectrum were registed at 420 nm ,540 n m a n d 6 4 5 nm. A c c o r d i n g t h e e l u e n t i n d e x molecular w e i g h t o f g r e e n o n e is t h e l a r g e s t among the complexes , the y e l l o w o n e is t h e smallest. The yellow complex is m o s t s t a b l e among the three , the reddish b r o w n o n e may transformed to green complex or some precipitate were occured w i t h i n c r e a s i n g the r e action time , the green one were changed to brown color in t h e aerobic condition . Thin layer c h r o m a t o g r a p h y (TIC). h i g h performance I iqu id c h r o m a t o g r a p h y ( H P L C ), ion e x c h a n g e chromatography were used to separated the c o m p l e x c o l l e c t e d f r o m GPC. UV, c o n d u c t i v i t y ,

flow beta d e t e c t o r applied results.

in t h e

and

autoradiography a l s o

experiment

to confirmed the

609

Monday, 2 September 1991

-

Tuesday, 3 September 1991

PO-2R1-43

Tuesday, 3 September 1991 PO-3L1-1

P.L. Zabel, L.M. G e c e l o v s k y a n d N.J. R i d e o u t : , L o n d o n R e g i o n a l N u c l e a r P h a r m a c y , D e p a r t m e n t of N u c l e a r M e d i c i n e , U n i v e r s i t y H o s p i t a l , P.O. B o x 5339, London, Ontario, C A N A D A

D. H U G L O LING.

DIETHYL MALEATE, AN INHIBITOR OF GLUTATHIONEt DECREASES RETENTION OF Tc-99m HMPAO AND In-lll TROPOLONE BY ISOLATED HUMAN POLYMORPRONUCLEAR LEUKOCYTES. G l u t a t h i o n e has b e e n p o s t u l a t e d to b e i n v o l v e d in t h e r e t e n t i o n of T c - 9 9 m d,l H M P A O in v a r i o u s tissues. Glutatbione(GSH) m a y be d e p l e t e d by diethyl maleate(DEM) through covalent binding. T o d e t e r m i n e w h e t h e r G S H m a y be i n v o l v e d w i t h t h e r e t e n t i o n of T c - 9 9 m H M P A O by p o l y m o r p h o nuclear leukocytes (PMNL), DEM was incubated w i t h P M N L p r i o r to l a b e l l i n g w i t h T c - 9 9 m HMPAO. T h e e f f e c t of D E M w a s also a s s e s s e d o n c e l l s l a b e l l e d w i t h In-lll t r o p o l o n e . P M N L w e r e i s o l a t e d f r o m h e a l t h y v o l u n t e e r s by P e r c o l l / p l a s m a gradients. The cells were then i n c u b a t e d (45 min) w i t h 2% D E M in p l a s m a w i t h 0.1% T w e e n 8 0 / 0 . 4 % ethanol. Control PMNL were i n c u b a t e d in the p r e s e n c e of p l a s m a a l o n e or p l a s m a w i t h 0.1% T w e e n 8 0 / 0 . 4 % ethanol. Cells w e r e w a s h e d w i t h PBS p r i o r t o i n c u b a t i o n ( 1 5 min) w i t h T c - 9 9 m H M P A O or I n - l l l t r o p o l o n e . Glutathione content was assayed by the e n z y m a t i c c y c l i c method. T h e G S H levels in P M N L d e c l i n e d by 91 ± 12% a f t e r D E M incubation. The l a b e l l i n g e f f i c i e n c y of T c - 9 9 m H M P A O d e c l i n e d by 86 ± 3.4% in t h e p r e s e n c e of DEM. Unexpectedly the l a b e l l i n g e f f i c i e n c y of In-lll t r o p o l o n e a l s o d e c l i n e d b y 75 ! 12%. S t a t i s t i c a l l y t h e r e is no d i f f e r e n c e between the percentage decline in l a b e l l i n g efficiency f o u n d for T c - 9 9 m H M P A O a n d I n - l l l t r o p o l o n e f o l l o w i n g D E M incubation. Additional a f f e c t s s u c h as c e l l m e m b r a n e p e r t u r b a t i o n s m a y be involved.

QUANTITATIVE COMPARISON OF 9 9 m T E C H N E T I U M ETHYL CYSTEINATE DIMER CEREBRAL UPTAKE WITH 133XENON REGIONAL CEREBRAL BLOOD FLOW USING SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY.

; D. L E Y S

; M.

ROUSSEAUX

D e p a r t m e n t s of N u c l e a r M e d e c i n e C . H . R . U . 59037 Lille, FRANCE.

The

aim

of

this

; M.

STEIN-

and N e u r o l o g y

study

was to r e a l i z e a of T e c h n e t i u m 99m (7 M B q / k g of 9 9 m T c E C D ) w i t h r e g i o n a l c e r e b r a l b l d o d f l o w (rCBF 1 i m a g i n g u s i n q 1 3 3 X e n o n i n h a l a t i o n m e t h o d and a d e d i c a t e d $ P E C T s y s t e m ( T o m o m a t i c 64). Five healthy volunteers and five patients (3 s u f f e r i n g f r o m i s c h e m i c i n f a r c t an~ 2 f r o m Alzheimer's Disease) were imaqed with both techniques. F o r e a c h study, 7 paired ROIs were drawn - cerebel]ar, anterior f~ontal sylvian, occiDita!, thalamic, s u p e r i o } fron i tal a n d p a r i e l a l areas. R e q i o n a l ~ t a n d a r d i z e d V a l u e s (8v) of 9 9 m T c - E C D , U ~ t a k e Indexes (UI) u s i n g c e r e b e l l a r a n d o c c i p i t a l v a l u e s as re i f e r e n c e , a n d A s y m m e t r y Indexes (AIJ w e r e comD@red quantitatively ~ith r e s p e c t i v e l y rCBF, F l o w I n d e x e s ( F I ~ a n d AI. Results in v o l u n t e e r s depict significant d i f f e r e n c e s in b o t h SV and rCBF v a l u e s l i n k e d to s e x or aqe a n d in r C B F l i n k e d to area. A r e a s w i t h h i g h e s t r C B F ( s v l v i a n and t h a l a m i c areas) a p p e a r s to be u n d e r e s t i m a t e d w i t h 99mTc-ECD bu% significant correlations were f o u n d b e t w e e n SV a n d r C B F (for v G l u n t e e r s : n = 70~ r = 0.286, o < 0.02 ; i n c l u d i n q all the studies : n = 140, r = 0.468, D < J. 01) a n d for t h e ten s u b j e c t s , b e t w e e n U7 and FI (p < 0.0001, u s i n q c e r e b e l l a r or o c c i p i t a l v a l u e s as r e f e r e n c e ] with better correiations with multiplicative m o d e l of r e g r e s s i o n . AI a r e h i g h l Z c o r r e l a t e d (r = 9.883, p < 0.0001 ~. ~mmc-ECD a p p e a r s no me a p o n e n n i e ± i n a i c a t o r of t h e c e r e b r a l p e r f u s z o n , e v e n if its u p t a k e u n d e r e s t i m a t e H i g h v a l u e s of rCBF, pec u l i a r l y in d e e p areas, p e r h a p s l i n k e d to an i n c o m p l e t e e x t r a c t i o n , as p r e v i o u s l y r e p o r t e d f o r 9 9 m T c - H m P A O a n d H o 1 5 0 c o m p a r e d to 1 8 F l u o romethane.

~ ut ah ny tl i t Ca yt si tv ee i n a tceo m p aDriimseorn

Abstract PO-2R1-43A see page 688 PO-3L1-2

PO-3L1-3

Katsumi Ishii, K. Nakazawa, H. Nishimaki, S. Nishiyama, T. Matsubayashi, T. Akutsu, S. Suzuki, F. Sakai. Kitasato University School of Medicine, Kanagawa, Japan.

C.H. Kay, P.Y. Wang, Y.L. Wang, L. Chang, S.O. Liao, S.J. Wang and S.H. Yeh Zaichung Veterans General Hospital, Taichung, Taiwan, R.O.C.

DEMONSTRATION OF REGIONAL CEREBRAL BLOOD FLOW WHILE ASLEEP BY THE SPECT BRAIN IMAGING USING 99mTc-HM-PAO

THE INAGING OF WBCS INFILTRATION IN NgMAN CEREBRAL INFARCTIONS USING Tc-ggm HNPAO LABELED WBC BRAIN SPECTS.

SPECT brain images using 99mTc-HM-PAO, which can visualize regional cerebral blood flow at the time of isotope injection, were obtained from nine patients with cerebral vascular disorder(s) and from three normal subjects when they were awake and asleep. Examinees were attached with EEGleads on the head and were suggested to fall asleep. When they became at the stage or ~I of sleep, which was determined by the EEG, 99mTc-HM-PAO was injected from the venous line previously accessed and SPECT images were obtained 30 to 60 minutes after the injection. SPECT images while awake were also obtained preceded by injecting 99mTcHM-PAO with their eyes closed for i0 minutes and they were compared with those while asleep in terms of the blood flow. The regional cerebral blood flow was the same in normal subjects either when they were awake or they became asleep. However, in 8 out of 9 patients with vascular disorder(s), blood flow at the lesion was demonstrated to have decreased when they were asleep. Since blood pressure monitored during the SPECT examination tended to decrease while they were asleep, decreased regional cerebral blood flow is considered to be correlated with blood pressure.

610

Because WBCsare regard to free-radical generation-a major component of ischemic injury, so WBCs i n f i l t r a t i o n should be well demonstrated in the regions of cerebral infarction. Twenty-six patients (23 males, 3 females, mean age: 66) of acute cerebral infarction were imaged by Tc-99m HBPAO labeled WBC (Tc-WBC) brain SPECTs and Tc-99m HMPAObrain (Tc-brain) SPECTs respectively after the onset of neurological symptoms and signs. The Tc-WBC were prepared by a modified method (gno K. et al. J Nucl Bed 1987;28:648), 36ml whole blood with 4ml ACD-A solution as anticoagulant and lOmCi Tc-99m HNPAOwere used for each scan. The labeling efficiency was 78±SD7%. Regions of interest vere placed in the whole bath hemipheres with summation of all transaxial s l i c e s in the Tc-WBC and Tc-brain SPECTs. The asymmetric indexes (AI) were calculated as [J (right-left) I / ( r l g h t + l e f t ) ] . Grouping of patients with cerebral infarction according as based on a c t i v i t i e s of daily living (ADL) at outcome; group 1:completely independent; 2:some but not daily a s s i s t a n c e ; 3:daily assistance; 4:hospital care; 5:dead. Subjects in groups 3 to 5 were considered to have poor outcome. There were no significant corrections in the AI of Tc-WBC with the AI To-brain (R=0.12) and the AI of Tc-WBC with the counts of peripherial WBCs (R=0.24) or neutrophils (R=0.27). The r e s u l t s shoved that the poor outcome patients had higher AI of Te-WBC than that of the other patients (0.065~SEH0.015 vs 0.027±SEM0.005, and P
Tuesday, 3 September 1991

PO-3L1-4

PO-3L1-5

K. 1%.zlcl, L.,§. Kapucu, B. Erba~;.. E Vare.~lu, C GL~le~, C.F. Bekdik, A. Ulupahin. Depts, of Nuclear Medicine and Psychiatry, ~ c e t t e p e University, 06100, Ar~:ara, Tdrkiye.

J.Knop, C.Fuchs, A.Thie2, R.Montz, G.Siebmannl Departments of Nuclear Medicine, Neuroradiologyl and Neurology2 University Hospital Hamburg, FRG

A PRELIMiNAR.Y REPORT OF A S~TJY ON CEREBRAL BLOOD FLOW CHANGES IN lf'~OR PATIEI.~S USING 99mTc-H]~'A0/SPECT,

EVALUATION OF VASODILATORYCAPACITY TO ACETAZOLAMIDE (ATZ) WITH 99mTc HMPAO SPECT IN ISCHEMIC CEREBROVASCUI/kR DISEASE (iCVD) Identification of patients with iCVD complicated by a restricted collateral capacity has been the domain of PET or 133Xe D-SPECT. The purpose of this study was to investigate the feasibility of 99mTcHMPAOSPECT for evaluation of vasodilitional capacity by ATZ. We studied 17 patients with iCVD (unilateral (bilateral) ICA occlusion n=ll(3); bilateral ICA stenoses >70% n=3) confirmed by angiography and transcranial Doppler sonography (TCD). Two consecutive SPECT examinations were performed 5 min. after injection of 370 MBq 99mTc HMPAO. After establishing the baseline study, the second tracer application started 15 min after injection of ig i.v. ATZ. The first data set (decay corrected) was subtracted from the second one. Using profile techniques (angle 6°), the cortical 99mTc HMPAO distribution was analysed in the most relevant tomogram (range 8-14 cm above the OM line). The change of cortical activity A% after ATZ was determined in both hemispheres (rH, IH). Calculation of changes in degree of side-to-side asymmetry for symmetric sectors D% [100x(l-r)/Max(1,r)] was used to evaluate change in regional flow distribution. Enhancement of D% by ATZ of>~0% was regarded as significant. 15 min after ATZ, mean 99mTc HMPAO uptake increased by A% rH 22+_13% and A% IH 20+14% (range 0,3-48%) in 15/18 studies. Eight of these 15 patients revealed a regional enhancement of D% by 15+_3% (range 11-20%) in compromised territories. The 99mTe HMPAO distribution pattern remained completely unchanged in seven cases indicating adequate collateral capacity consistent with results of TCD. ConclusiQ_~: These results demonstrate the adequacy of this procedure for imaging ATZ increased rCBF and respective changes of regional flow distribution in cases with restricted collateral capacity. ATZ 99mTc HMPAO SPECT appears a promising too1 for regional assessment of cerebrovascular reserve capacity in iCqD.

REGIONAL DEPRESSI\{

Regiolm~l cerebral blood flow changes were evaluated in pts with major depression diagnosed with DSMIII-R criteria (6 with si1~le and 14 with recurrent episodes) and in i~ healthy voD_Lnteers all right ha.r~ed, Mean ages of patients almJ controls were 35.9 (S.D:10.6) and 33.38 (S.D~7.5), respectively. Severity of depression ~as assesed by using 17-ite~ Hamilton Depression Scale. All pts but 5 were off psychotropic medicine for a m i n i m m of 5 days. 5 pts received 5 m~ diazepam b.i.d, orally for 2-3 days only. After administiration of 2Q mCi 99mTcH ~ A O SPECT study %9.s done. Coumt/pixel ratios to whole slime were calculated for 32 regions in orbitomeatal plane. Additionally, left/right ratios were obtained. Statistical significance between the rCBF of two groups was determined by using !~m~}~itney U test. Reduction of rCBF in left prefrontal and both of the temporal regions we.s significantly low in pt£ compared to control subjects (p<0.05). The difference between the pts with and without medication in rCBF of left prefrontal cortex Tmas significant (p<0.05). Diazepam patients Pm,d rCBF increases in that region, qT~ere was no correlation between the reduction of CBF in cerebral regions and Hamilton scores, except for a significant negative correlation between left temporo-occipital rCBF ar~ Hamilton scores (p
PO-3L1-7

PO-3L1-6 Krolicki L., M a z u r ~

W. ,(irabowskiZ.

Department of Nuclear Medicine and Departmentof Neurosurgery

J.T. Kuikka, V. Laulumaa, K. Bergstr~m, P. Vainio, E. L~nsimies, P. Riekkinen, Kuopio U n i v e r s i t y Hospital, Kuopio, Finland

Cotmty Ho~pital,WarsawKondratowicza 8

IMAGING AND CEREBRAL KINETICS OF 1-123 IOMAZENIL IN FOCAL EPILEPSY

99m-Tc-f94-PAOSTUDY C~ CEREBRAL BLOCO FLOW IN PATIENTS WITH SUBAP~C~NOXU HAm~OR~A~ /S~/. The study investigates the role of HM-PAO and SPECT in SAH. 37 patients were examined /50 studies / and in 25 of them HM-PAO examination showed derangements of cerebral blood flow: Hunter/Hess No No path. clinical grade I II III IV V

5 i0 9 8 5

0 3 9 8 5

In 23 cases HM-PAO study was performed immediatelly before angiography and in 9 cases before CT.In I0 patients with angiographically defined vasospasm,HM-PAO studies were also pathological. In 13 cases without symptoms of vasospasm in angiography,HM-PAO studies were normal in 6,but pathological i 7 cases. CT showed only in one case an abnormal result /intracerebral haematoma/. Focal hypoperfusion as a most common finding in HM-PAO studies can be observed frequently in patients with SAH.HM-PAO results correlates with a clinical state of the patients. HM-PAO study is more sensitive than angiography and CT in evaluating ischemic complications in patients with SAH.

SPECT imaging of 1-123 lomazenil in epilepsy has recently been reported to be a promising method to l o c a l i z e the e p i l e p t i c focus. We investigated i n t e r i c t a l l y the cerebral kinetics and d i s t r i b u t i o n of t h i s t r a c e r in 7 patients with focal epilepsy. A f t e r an iv. i n j e c t i o n of 150 MBq of 1-123 Iomazenil a dynamic study was undertaken in AP position (30 frames, each 2 sec and 8 frames each 30 sec). Seventy f i v e minutes l a t e r a SPECT study was started (3600, 64 angles and each 20 sec). The transaxial in OM l i n e , s a g i t t a l and coronal slices (6 mm thick) were reconstructed a f t e r Wiener f i l t e r i n g and uniform attenuation correction of 0.11 cm-1. Dynamic Study. Time a c t i v i t y curves were drawn from the ascending aorta (input) and from the both hemispheres (residues). A deconvolution routine was used to find a "true" impulse response function of the brains and the c a p i l l a r y e x t r a c t i o n of Iomazenil, E to the brains was estimated using the Sejrsen's method. The parametric image to show the regional cerebral perfusion was calculated. SPECT. The tomographic slices were v i s u a l l y surveyed. The r e s u l t s showed the high cerebral trapping of 1-123 Iomazenil, E being 0.82 +/- 0.08 (mean +/- SD). The q u a l i t y of SPECT images were e x c e l l e n t and the correct EEG e p i l e p t i c foci was found in 5/7 cases. Our experiments in epilepsy a f t e r t h i s small serie is that 1-123 Iomazenil seems to be s l i g h t l y b e t t e r than Tc-99m HMPAO (over 60 patients studied) but is rest r i c t e d by the everyday a v a i l a b i l i t y and price.

611

Tuesday, 3 September 1991

PO-3L1-8

PO-3L1-9

G, Leinsinger, S.R.G. Stodieck, R. Wedel, B. Steinhoff, and C.-M. Kirsch Depts of Nuclear Medicine and Neurology, University of Munich, Klinikum GroShadern, Germany

M. Lorberboym*, M. Feibel +, and L. Lieberr~ln*, *Depart~cent of Nuclear Medicine and +Department of Diagnostic Radiology, Tel Hashon~er Medical Center, Tel Aviv University Sackler School of Medicine

INTERICTAL 99mTC-HMPAO-SPECT AND BENZODIAZEPINE RECEPTOR IMAGING IN PARTIAL EPILEPSY The aim of the study was to investigate the clinical value of interictal HMPAO-SPECT and benzodiazepine receptor imaging using 123-I-Iomazenil (IMZ) in patients (pts) with focal epilepsy. The study includes 57 pts. In 25 pts MRI detected morphological lesions which correlated with the EEG focus. In 32 pts MRI was normal. 8 of these 32 pts n e v e r had been treated with antiepileptic drugs. 24 pts were treated with carbamazepine, valproate or phenytoin. No drugs known to interact with the benzodiazepine receptor were given before IMZ-SPECT. In 57 pts cerebral perfusion was assessed 30 rain after injection of 500 MBq 99m-Tc-HMPAO. In 17 pts additional benzodiazepine receptor imaging was performed 60 min after injection of 185 MBq 123-I-IMZ. Data were acquired using a doubleheaded gamma camera equipped with a high resolution collimator. The images were visually evaluated without knowledge of other results. In pts with morphological lesions a focal abnormality was visualized with HMPAOSPECT corresponding to the EEG focus in 17/25 pts (sensitivity 68%; specificity 92%) and with IMZ-SPECT in 4/7 pts (sensitivity 57%; specificty 100%). In pts with normal MRI the focus was localized with HMPAO-SPECT in 13/32 pts (sensitivity 38%; specificity 94%) and with IMZSPECT in 5/10 pts (sensitivity 50%; spezificity 90%). However, in those pts without antiepileptic drugs sensitivity of HMPAO-SPECT was 63%, in pts on antiepileptic medication 27%. A similar tendency was observed with IMZ-SPECT. In conclusion, interictal HMPAO-SPECT and IMZ-SPECT are highly specific methods to localize epileptic foci. In pts with normal morphology in our series sensitivity seems to depend on the presence of antiepileptic treatment. Further results on pts before and after antiepileptic therapy will be presented.

TL-201 SPECT IN DETERMINING RESIDUAL MALIGNANT BRAIN TUMOR BURDEN Patients with [~lignant brain tumors, who received radiation and/or chenDtherapy, were studied to identify residual tumor tissue. Because of edema and tissue necrosis, residual or tumor recurrence has been uncertain with FLRI or CT. 23 patients were imaged after IV injection of 4 nCi TI-201. We used an Elscint SP4 gamma camera acquiring 60 fran~s in 64X64 nmtrix. Reconstruction was done using a Metz filter in sagittal, transverse and coronal planes. SPECT results were compared with CT and/or l~I studies within 7-10 days. Tumor to nornml contralateral tissue ratios were estinmted for all lesions. 16 patients had positive SPECT studies and 3 were negative. 4 showed post-surgical changes of increased uptake in the skull but no intracerebral abnormalities. SPECT studies generally showed lesions that were more discrete than CT or MRI suggesting that edema, fibrosis and necrosis are not imaged by TI-201 SPECT. Additional lesions were noted that were not seen on CT or MRI. All lesions had tunor to nornml tissue ratios above 2.0. Our results suggest that TI-201 SPECT provides the most accurate technique for assessing the response to therapy in patients with brain tumors. CT and MRI do not differentiate recurrent or residual viable tumor from tumor necrosis or cerebral edema. A tumor to normal tissue ratio over 2.0 is strongly suggestive of high grade malignancy. Compared with other available modalities TI-201 SPECT provides the most accurate representation of tumor burden following chemotherapy and/or radiation therapy.

PO-3L1-10

PO-3L1-11

G.Lucignani, G.Paganelii, A.Zenorini, P.Magnani, F.Zito, C.Messa, S.Todde, G.Scotti, MC.Gilardi, H.Maecke and F.Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy; University of Basel, Basel, Switzerland.

J.L I ~ . 7 ~ G. D ~ . :-. :~8£---£'.~. "-'~2'Z~:~, '. ~:. (- t_~.,2@.~1, C. CCDLZ ~r~ N. ~ £ ~ 7 . : : :#;BT.]TZ-PT~IS 13 ~4.1:

SPET/RADIOIMMUNOSCINTIGRAPHY, PET/FDG, AND RADIOLOGICAL FINDINGS IN PATIENTS WITH CEREBRAL GLIOMA. Techniques of morphological imaging such as X-ray CT and MRI may be inconclusive for the diagnosis of cerebral gliomas and also in the post therapeutical follow-up of these tumors when the possibility to differentiate recurrence or change in histological type is hampered by the presence of scar tissue and the effects of radionecrosis. PET with FDG is among the methods useful in the diagnosis of gliomas. A method based on SPET, however, is desirable due to the wider availability of SPET equipment. For this purpose radioimmunoscintigraphy (RIS) based upon the use of an anti-tenascin monoclonal antibody (MoAb) and SPET has been proposed. To evaluate the combined use of SPET/RIS, PET/FDG and morphological imaging techniques for the diagnosis of cerebral glioma, we studied 8 patients with istologically documented diagnosis of cerebral glioma. RIS was performed using a new method based upon a 3-step technique (anti-tenascin biotinylated MoAb, cold avidin and [Tc-99m]PAO-biotin). PET/FDG, MRI and X-ray CT were performed using conventional protocols. MRI or X-ray CT allowed us to identify 4 definite gliomas. FDG abnormal uptake was observed in the 4 subjects with abnormal radiological findings and in 2 additional subjects. SPET/RIS was positive in 5 of the 6 FDG positive subjects and in 1 of the two FDG negative cases. These results demonstrate that the combined use of PET/FDG and SPET/RIS based upon the 3-step method can improve the diagnosis of glioma.

612

~:-~,_.9 ~ E.:~'-~~ . ~ . ~ iT321-.

.~ '. IN. J . ~ .

~.',_FZ

~)T~C~'_J-&.

~ Y

_~b:2

':~..~ .,~ gEe.is of ~_..~ st:.~,,'.~r~._ fm ' :/assess Diag:~_,~st.:c Ser~itivity (P. S. %) of 9c 99,,'~ vers~s t~T S~-~ ~ s r e:~ appr~,,'~d ~::,Aprotocol. 2/cm~pare ~ , to ~ ' P. 8. ~ t ~ 24 h. 3,' e ~ l ~ t e b r a ~ t ~ distributi~: of t.he 2 tracers. ~s~ last 2 points ~ r e bela~g~ng_ to a ~ecific i o ~ l protocol appr~,x£ ~:.. ~- our Ethical Cc~mttee :5 "- n o ~ : ys) hid e:ly t~e early ECD-~L'T (74,5 ± 25.6 ~ : p.i). i: pati~ts ,~ Ferrules a~nd i4..Wiles, maan ,~:e_ 66.4 .~ ~~4..4 :~>. suffering, fro~ subcortical (7/18) a~l cortical ~',,'~:--'~, ~.~ strokes ~ early (ECDI :92 : 21 ::in p.i) ~ dele~._-ed .(.~: 279 ± 76 rain p.i) Dr: ~ on a ~ n of I0 da.:~ after stroke ~ ~., da:~ after t~ storm. 24 is_q::s later, _-~:~-" ~'q "(]]f}l " 28 ± 13 rain p.i) ar~ d e ~ T e d ( ~ 2 p i) I~P SPECT were perf0rm~ YV~r ~,_ject6d doses ::ere 7.:% ? ~± 80 BBq for F£D ~ ~Sm 8 ~ 320 ± 38 i~.: for ~.~ 123 'Differ~nt%al activity (D.A %) ratio ~,as oalc,.~t~ frs~ the same ROI delineated on h~9.oactive ~:i controJ~_terai r~J~.l areas. ~ m:_~: DA % 9~.s of -29.2 ~ECD~,~. -34 ..___~.'~,-" ~.,qT~ -!6.7(]:~1). -ll .-,. .... . er~ DS :~: accordJ~j to ~.riar.:or, :aL~ulatad cn r m r m l wl~z~teers (DA % = 4 = 3.3..--: = 5::L:: R3I) ,,:s r~ecti:ml7 83.3 • 88.8 " 72.2 • ::.:._: ~,: Correlation c0effici~ts f r ~ DA ~¢ere DL~.i./EJ~;= 894 E.FT~II'LMDI - O.~ .U,? . . . .TT, ~'~'~"~'g--~ ,~f~o~l ~,.-~c~-'--"D~~,.-~.,_~?~iit? ~ o.:~trest ~.,~re better for ~ 2 VS E @ i s:_~est.lz'~ sc:e : ~ n DA %~.s si,~:~i,:~_r:t.l:l lo~!er ~,-_,r ~:~,cc::-:±9-.! lesi_'y,-2 ,-.:-...5%) sc:~e.rs: t.o csrt.isal !ssi.:::~:::_4=- 2: £} Z:~, /.et..t.e'rt:r~::Z_2

2,'Fiiii2~C-zz:<~.: ::st :t:.:r::C <::.1:.- -

Tuesday, 3 S e p t e m b e r 1991

PO-3L1-12

PO-3L1-13

N i c k e l , H. S t e i n e r t , S. F i s c h e r , . :~ahn Dept. of N u c l e a r M e d i c i n e , J o h a n n e s berg Universit~t, Mainz, FRG

L.A.O'Tuama, R.M. Scott, P.McL.Black, S.E.Sallan, N.J.Tarbell, J.Ulanski, R.T.Davis, S.T.Treves. Children's Hospital and Harvard Medical School, Boston, MA.

O.

Guten-

SIMULTANEOUS MEASUREMENT OF ]{EART A N D BRAIN FUNCTION USING 99M-TC-HMPAO As s h o w n p r e v i o u s l y the u p t a k e of 9 9 m - T c H M P A O in b r s i n d e p e n d s on H M P A O e x t r a c t i o n and c a r d i a c o u t p u t . In t h i s s t u d y a m e t h o d h a s b e e n e v a l u a t e d to g e t t h e s e p a r a m e t e r s by a s i n g l e i n j e c t i o n of 9 9 m - T c - H M P A O . M e t h o d a n d m a t e r i a l : A f t e r i n j e c t i o n of 550 M B q 9 9 m - T c - H M P A O a f i r s t - p a s s s t u d y of the h e a r t is a c q u i r e d (20 i m . / s e c ) . Inflow of a c t i v i t y i n t o the b r a i n is r e c o r d e d simultaneously by a NaJ probe interfaced to the c o m p u t e r , i0 m i n u t e s a f t e r i n j e c t i o n a S P E C T s t u d y of the b r a i n is p e r f o r m e d . F r o m the f i r s t - p a s s s t u d y of the heart ejection fraction and cardiac output is c a l c u i a t e d . F r o m the b r a i n c u r v e the H M P A O e x t r a c t i o n is c a l c u l a t e d : u s i n g the aortic time/activity c u r v e as i n p u t f u n c tion. O n o v e r i00 p a t i e n t s t h e d a t a a c q u i s i t i o n h a s b e e n p e r f o r m e d . R e s u l t s : ]]sing t h e H M P A O f i r s t - p a s s h e a r t s t u d i e s the c a r d i a c o u t p u t c o u l d be c a l c u l a t e d p r e c i sely. The HMPAO extraction came out lower than reported previously (less t h a n 50%). T h e r C B F , c a l c u l a t e d f r o m u p t a k e in b r a i n , e x t r a c t i o n a n d c a r d i a c o u t p u t , w a s in the correct range. CQnclusigns; The method a f f o r d s a l m o s t no a d d i t i o n a l time, t h e r e f o r e it c a n be d o n e o n a r o u t i n e b a s i s on all p a t i e n t s to g e t a u s e f u l q u a n t i t a t i v e information about rCBF and heart function.

201-TI/99mTcHMPAO SPECT IN CHILDHOOD BRAIN TUMORS. 201-thallium chloride (TI) is a promising tracer for functional assessment of adult brain tumors (i). We have now studied 27 childhood brain tumors with SPECT: Thallium chloride (TI) (1.3-1.8 mCi iv), followed (n=13) by 99m-Tc-HMAPO (8-18 mCi iv), to assess cerebral perfusion. T1 uptake was increased in histologically confirmed recurrence (including 4 astrocytic tumors, and 4 medulloblastomas/primitive neuroectodermal tumors). Verified total removal of tumor showed normal or minimally increased uptake (including 3 astrocytio tumors, 2 ependymomas, and 1 medulloblastoma). T1 failed to detect 5 tumors (4 posterior fossa nona s t r o e y t i c lesions, and a low-grade temporal astrocytoma; however, the latter lesion was detected on follow-up SPECT). The sensitivity and specificity of 201TI SPECT for detection of childhood brain tumors was 76.9% and 93.3%. Tumor uptake of T1 was quantified using a modification of the image gray scale allowing reference to areas of brain that were extravascular snd showed no visually perceptible 201-TI uptake. Operatorselected points were placed on transaxial slices, and used by the computer to define rectangular regions of interest measuring i0 x i0 pixels (1.13 cm/pixel). In regions so analysed, the mean tumor-to-normal brain ratio for T1 was 25:1 (exceeding b y ~ 5-fold values obtained with PET agents). In both Tl-avid and nonavid cases, HMPAO distribution ranged from normal to increased to d e c r e a s e d at the site of tissue abnormality, and "diaschisis" was frequent in the remaining neuraxis. Changes in tissue perfusion did not correlate with T1 abnormality, but were characterized in only one false negative study. (i) Kaplan Et AI: J. Nucl. Med. 1987; 28:47-52.

PO-3L1-14 E. Paulesu, D. Perani, V. Bettinardi, M.C. GiJardi, R. Casati, M Franceschi, F. Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy.

PO-3Ll-15 C.Pozzilli. H.G.Grasso, P.Pantano, A.Pace, D.Intiso, A.Padovanl,G.LlenzI, C.FieschI. Department of.Neurological.Science., University of Rome. and "Centro resldenziale Cllnica Slucia", Rome

TRANSHEMISPHERIC DIASCHISIS IN ACUTE STROKE: A LONGITUDINAL [F-18]FDG AND POSITRON EMISSION TOMOGRAPHY (PET) STUDY.

CEREBRAL BLOOD FLOW PATTERNS IN POSTSTROKE DEPRESSION Poststrokedepression(P,SD) has beenreported in approximately 30~ of patients attandlng a stroke clinic and does not appear to be simply a reactlo[1to the physical impairment. It ls still debatedwhetherthere is a relationship betweenP$D and CT lesioncharacteristic such as extent and location. In the presentstudywe investigatedthe possibility that neurophysiologic examinationswith 5PEC]"wouldenhanceour knowledgeon the reasonsthat lead to PSD. We examined 20 patients with ischemic stroke, obeerved within 3 monthsfrom the clinical onset They were submitted to a full neurological and neuropsychologlcelassessment. Depression was tested using Hamilton, Zungand Back scales. A11 pattantsunderwentto CT/MRI study and SPECT examination by using Te 99m HM-PA0 and Tomomatic

The reduction of regional cerebral blood flow and metabolism in the hemisphere contralateral to unilateral cerebral stroke (transhemispheric diaschisis) has been reported by PET in acute phase. Serial studies on the same patients, in acute and chronic phase of stroke, can provide new information on the occurrence and evolution of transhemispheric diaschisis. Seven patients, admitted for acute unilateral supratentorial stroke (6 infarcts, 1 hemorrhage) of limited extent on CT/MRI scanning, undenNent a steady-state 2[F-18]-Fluoro-2-deoxy-D-Glucose (FDG) and PET (Siemens/ECAT 931/04-12 CPS) study within two weeks and three months after stroke. The comparison of regional cerebral glucose metabolism of patients in the acute phase with matched normal values demonstrated the presence of a significant glucose hypometabolism involving both the ipsilateral damaged and, to a minor degree, the contralateral unaffected hemisphere. In all the patients a crossed cerebellar diaschisis was present in acute phase. In the follow-up studies a significant (p<0.01) increase of global hemispheric cerebral metabolism on both sides was demonstrated. A cerebellar asymmetry was still present in four cases, These results confirm the presence of a transhemispheric diaschisis in the acute phases of stroke, even for cerebral lesions of limited extent. The follow-up studies also demonstrate the possible metabolic recovery both of the damaged and undamaged hemisphere in the chronic phase of stroke.

564, Preliminary results Indicatethat PSD patients showedgreater cerebral bloodflow abnormalitiesthan thesewithoutdepression,and the extents of hypoperfused area was much greater than the corresponding CT hypodermlty. Furthermore tt seems that the mechanisms leading to deprasslon"era different depending on the side of hemispheric hYpoperfuslon. PSD patients with left hemispheric laslons showed o predominanthypoperfustonin the frontal areas, while posterior areas were mainly involvedin patientswith right side lesions.

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PO-3L1-16 .].Rosso~J.L.Moretti~F.Lhote,C.Belin,C.Dresen,B.3arousse~ C.Geny~L.Guillevin. H6pital Avicenne~ Bobigny, France.

EARLY DETECTION OF REGIONAL CEREBRAL PERFUSION A B N O R M A L I T I E S IN HIV PATIENTS B Y H M - P A O SPECT IMAGING. HIV oncophalopathy is the most common cerebral illness associateowitli HIk7 infection. Its diagnosis is often delayed because the i n i t i a l symptoms are subtle and usually occur late in the course of the disease. We studied the value of HM-PAO SPECT for the early detection of HIV central nervous system (CNS) involvement. 35 patients (16 drug addicted, 19 homo or heterosexuah9 stade III~ 6 ARC,29 AIDS), without psychiatric or neurological symptom were investigated using GE 400 AC/STARCAM system and filtered back projection on 64 views. Correlating psychometric evaluation was available in 2/4 pts and CT or MRI studies were performed in 33 pts. Diagnosis of cerebral HIV involvement was made by excluding other causes of CNS disorders by combination of historical details, serologic evaluation and radiographic studies. Psychometric tests were slightly disturbed in 9/2/4(37%). CT/MRI images showed cerebral atrophy or white matter abnormalities in 5/33(15%). By contrast~ HM*PAD SPECT was abnormal in 25/35(71%). Perfusion impairment was mainly located in the frontal high parietal lobes. In 12 pts the decreased uptake was extensive. The percentage of abnormal perfusion scans in stade III,ARC~and AIDS patients was respectively 44%,67% and 85%. Moreover we found nearly the same percentage of abnormal scans in drug addicted(69%) than in non drug addicted patients (74%). Conclusions:l) HM-PAO SPECT identifies impairment of brain perfusion in HIV paLients~ before any neurological sign occurs~2)it appears a valuable tool for detecting early HIV involvement of CNS~ whatever patients are drug addicted or not.

PO-3L1-18 M. Gericke, U. StabelI,D. Douglas, M, Arnan-Thiele, R.Hauser Praxis fSr Nuklearmedizin Dillenburger Str. 1, 1000 Berlin 33, FR Germany HIGH RESOLUTION HMPAO-SPECT WITH NEW 3 HEAD CAMERA IN COMPARISION WITH SINGLE HEAD CAMERA IN PATIENTS WITH CEREBROVASCULAR DISEASES Brain-SPECT with 99mTc-HMPAO is a highly sensi tive and specific method to evaluate brain perfusion disorders in cerebrovascular diseases (CVD). The limits of the method is the poorly spatial resolution particularly in the area of the brain stem and basal ganglia. Indirect signs like the crossed cerebellar diaschisis could not be seen in all ol=the patients. Therefore detection of CVD in risk patients with hypertension who often showes only minimal changes in the lenticostriate area or in the internal capsule is quiet problematic. High resolution SPECT with the new 3 Head gammacamera ( Prism 3000 , Picker ) with UHR fan beam collimators has an intrinsic spatial resolution of about 3,75 mm which is compatible to CT scan. To investigate the advantages of high resolution SPECT in comparision to SPECT done with normal single head camera, comparative studies in approx. 50 patients with suspicion of CVD has been performed with Single Head SPECT ( Picker SX 3 0 0 , slanthole collimator, 64x64 matrix and iterative reconstruction ) with 555 mBq 99mTcHMPAO followed by SPECT with Prism-Camera ( UHRFan beam, 128xl 28 Matrix, iterative reconstruction ). The first results showed a superior image quality and better delineation of the basal ganglia and brain stem. The final results of the study will be discussed.

614

PO-3L1-17 Th. E. Schlaeofer*, G. K. v. Schulthess**,P. A. Schubiger***,H. RSsler****, H.-U. Fisch* *PsychiatrischeUniversit~.tspoliklinikBern, **Klinikf,",rNuklearmedizin, Universi~tsspital Zt~rich,***Paul Scherrer Institut,WSrenlingen, .... Abteilunaf~r Nukl~.nrmedizin,InselsDitalBern RELATION BETWEEN HEPATIC FUNCTION AND W A S H - O U T OF 1-123 IOMAZENILE AFTER DISPLACEMENT WITH FLUMAZENILE FROM THE BRAIN Introduction: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome in patients with chronic liver disease characterized by decreased mental capacity. HE is partly mediated by a hyperactivity of the inhibitory GABA-ergic system. PET-studies suggest that the GABA-receptor system in humans with HE is altered. Patients and Methods: 24 outpatients (age 52 + SD 1 lys, 12 with and 12 without HE), with biopsy proven cirrhosis with a mean galactose elimination capacity (GEC, an established marker for the metabolic capacity of the liver) of 4.5 :t: 1.3 mg/min/kg bodyweight (normal value=6.0) were administered 3 mCi 1-123 iomazenile i.v. After 50 min 0.05 mg/kg bodyweight flumazenile was injected i.v. to displace the tracer from its binding to benzodiazepine receptors. Activity from the head was monitored with a single probe. The resulting wash-out curves after the injection of flumazenile were fitted biexponentially. Results: Mean values were for kl: 0.141 _+ 0.056 and k2: 0.013 + 0.005. A significant correlation between GEC and k2 (r=0.54, p<0.01) was obtained. Conclusions: The results seem to indirectly support animal findings suggesting a deranged GABA-ergic system in humans even with minimal HE. The data are consistent with the assumption of down regulation of benzodiazepine recep• tors in HE.

PO-3L1-19 J Naveteur -M Steinlinq - J C1 Roy - M Rousseaux - R Vergnes . Universities of LILLE I and II.Department of N u c l e a r Medecine. 59037 LILLE Cedex. FRANCE. A S Y M E T R I C A L E F F E C T OF E M O T I O N A L S T I M U L A T I O N ON THALAMIC BLOOD FLOW. Hypothesis of hemispherical specialization o r e m o t i o n a l f u n c t i o n s gave rise to an extended literature but was p o o r l y investigated with regional Cerebral Blood Flow (rCBF) measurement. Especially, i n f o r m a t i o n s on asymmetrical involvement of s u b c o r t i c a l structures are rarely available. One of the purpose of the p r e s e n ~ experiment was then t 9 compare" r C B F d u r i n g n e u t r a l a n d emotiona% s t i m u l a t i o n . S u b j e c t s w e r e 2u r i g h u n a n a e n h e a l t h y f e m a l e s w h o w e r e of l o w and h i g h u r a i t - a n x i e ~ y as a s s e s s e d Dy t h e C a t t e l l s S e l f A n a l y s i s S h e e t . r C B F w a s m e a s u r e d by one Xenon innalation m e t h o a with a aeuicateu S P E C T T o m o c a m e r a (TOMOMATIC 64). P a i r e d reg i o n s zo i n t e r e s t (ROIs~, a p ~ o ~ i aerineu, • n c l u d e d the f r o n t a l ann u p p e r frontal cortex, the parietal and upper parietal cortex, the temporal lobe and tn~ thalamus. Two measurements were performed when subjects were listening to neutral or emotional tape recorded sequences composed respectivelly of everyday rife or fear inducing noises. The m a i n e~fect observed (ANOVA) was a significant in~ t e r a c t i o n of the a u o i t o r y w i t h t h e sine o~ the t h a l a m u s (F(1/16) = ~.85, MS = 189.1, D <.01~. A l t h o u g h t h e s i m p l e e f f e c t s d i d n o % r e a c ~ an a c c e p t a b l e s i g n i f i c a n c e level, the apparent, asymmetry was of opposite direction uuring ~ne n?utral ~ Right ~ Left ana auring the emotiona~ stimulation: Left>Right . This c h a n g e w a s m a i n l x r e l a t e d to a d e c r e a s e of the r i g h t t h @ l a m z c rCBF b e t w e e n the n e u t r a l ano e m o t i o n a ~ s t i m u l a t i o n s w h e r e a s the left rCBF seemed similar in both conditions. This effect was not influenced by the subjects'anxiety. For the c o r t i c a l rC~F no s i a n i f i c a n t i n t e r a c t i o n w a s o b s e r v e d b e t w e e n ~ h e side and the stimuli. The results obtained in the thalamus were in agreement with an hypothesis of l a t e r a l i z e d c e n t r a l p r o c e s s i n g of e m o tions.

Tuesday, 3 September

1991

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M S t e i n l i n g - J C1 Roy - R V e r g n e s - J Naveo f L I L L E I and II. teur . U n i v e r s i t i e s D e p a r t m e n t of N u c l e a r Medicine. C.H.R.U. 59037 LILLE cedex FRANCE.

K. Te,m~ki, T. Okuno, Y. Iwasaki, Y. Yonekura, J. Konishi, H. Mikawa. Department of Pediatrics and Nuclear Medicine, Kyoto University Faculty of Medicine, Kyoto, Japan

TRAIT-ANXIETY AND C E R E B R A L BLOOD FLOW. The p u r p o s e of the p r e s e n t e x p e r i m e n t i n v e s t i g a t e the r e l a % i o n s h i p was to f u r % h e r b e t w e e n a n x i e t y and r e g i o n a l C e r e b r a l B l o o B Flow (rCBF), taken into account the state and trait dimension for anxiety. Accoraing to p r e v i o u s data, the assumption was f o r m u l a t e d t h a t a n x i e t y w i l l induce not only a d i f f e r e n tial activation of s e v e r a l b r a ~ n a r e a s but also asymmetrical activations. Subjects were 20 r i g h £ handed h e a l t h y females. They p r e s e n teu extreme t r a i t - a n x £ e t y scores ( C a % t e l l ' s Self Anal~sis Sheet). r ~ B F w a s m e a s u r e d by rne Xenon inhalation m e t h o u u s i n q a TOMOMATIC 64. P a i r e d r e g i o n s of i n t e r e s ~ (ROIs~, a p r i o r i aelineu, incluoed the mrontal a n u superior f r o n t a l c o r t e x , the p a r i e t a l and sup. parietal c o r t e x , the t e m p o r a l lodes and the %halamus. Two measurements were performed to n e u t r a l or when subjects were listennig emotionaI tape recorded ~equences. At the end of t h e e x p e r i m e n t a l s e s s f o n , s t a t e a n x i e t y w a s r e t r o p e c t i v e l l y a s s e s s e d ~ A c c ? r d i n g to ANOVAj anxiety inauceu signizicanrly lower rCBF ~n several areas .It snows that such and e f f e c t appeared-to be linked to both state or t r a i t a n x l e t y . F o r t h i s l a t t e r %nalysis, the p o p u l a t i o n was uiviaed by the m e a i a n into low an~ high state anxiety subjects:The m a i n . r e ~ sult oStainea as r e g a r d to the nemispneracal specializ'ation of a n x i e t y w a s a s i g n i f i c a n t ANXIETY x HEMISPHERE interaction in the high p a r i e t a l c o r t e x f F ( i / 1 6 1 = 1 3 . 0 9 t p < .01 for t r a i t anxiety and ~ / ( 1 / 1 8 ) = 5.73, p <.05 for state anxiety). I n b o t h ?ases,. t h e . e I ± e c t cnaracterizea especlaliy itselz oy a nilateof r i g h £ > l e f t d a r e c t i g n in ral d i f f e r e n c e t h e n i g h a n x i o u s s u n ~ e c t s . A n a l y s i s oi variance did not lead to such a siqnificant res u l t in the thalamus~ but c o r r e l a t i o n s between state a n x i e t z a n d rCBF were negative and signizicantly n i g h e r in t h e l e f t sine, (r = 0.~6, dF = 18, p < 05 in the left side and r = 0,27, NS, in ~ h e r i g h t s i d e ) . The p r e s e n t experiment lead to consioer t h a t t h e e z ± e c t s om anxiety on rCBF hat not to De neglecteu.

PO-3L1-22 H Terada, T Gomi, T Furukawa, S Murakami, M Nagamoto, A Ku~:ajima, Y Hiramatsu, H ~atsushima, S Iwabuchi', H Same,iima', N Yoshii'. Dept. of Radiology ~ Dept. of Neurosurgery', Toho Univ. Ohashi Hosp. (Tokyo, Japan) USEFULNESS OF HMPAO SPECT COMBINED WITH THE ACETAZOLAMIDE TEST IN MOYA MOTh DISEASE Consecutive brain H~PAO SPECT studies before and after DIAMOX administration were performed within a short period of 30 min on 5 ?mtients (4 women, 1 man), aged I0 to 47

years old (mean 33 years) with Moya-moyadiseases. All patients had bilateral encephaio-duro-artrJosynangiosJs (EDAS). In 2 patients, HMPAO studies were performed once after EDAS operation. In other two patients, studies were performed before and 4 months or 16 months after the operation. In the last patient, studies were performed 6 months and 12 months after the operation. All studies showed decreased perfusion reserve in anterior

cerebral artery territories and middle cerebral artery territories. In 3 patients who received follow-up studies, although baseline images showed no significant interval changes, post-Diamox images showed apparent improvement of perfus~on reserve. In these 3 patients, development of collateral pathway on IVDSA, disappearance of rebuild up on EEG or diminishing involuntary movement showed their good clinical course corresponding to improvement of perfusion reserve. In conclusion, consecutive HNPAO SPECT studies before and after DIAMOX administration are quite useful for the evaluation of EDAS effects on cerebra] perfusion reserve in patients with Moya-moya desease.

REGIONAL CEREBRAL BLOOD FLOW ON IMP-SPECT IN PATIENTS WITH TUBEROUS SCLEROSIS: COMPARISON WITH MRI AND EEG FINDINGS. Epilepsy is very common in tuberous sclerosis (TS) with various types of seizures occuring. To identify the focus of paroxysmal neuronal activity causing epilepsy in TS, regional cerebral blood flow (r-CBF) was assessed using SPECT with 1-123 iodoamphetamine (IMP), and the correlation with serial interictal EEGs and organic changes shown by MRI were investigated in 19 patients with TS. There was a general irregularity of cortical IMP uptake and retention in TS, and two thirds of the cerebral regions with high intensity in T2 weighted MRI images (cortical tubers) showed decrease in rCBF. Among the cortical regions which showed epileptic foci consistently in serial EEGs, none showed abnormal r-CBF without lesions on MRI. The relationship between the current status of epilepsy and the severity of MRI and SPECT findings was also investigated. The patients with fewer affected regions on MRI and SPECT showed higher tendency to become seizure free. Those with more affected MRI regions had seizures more frequently, whereas there was no definite correlation bewteen seizure frequency and the number of affected SPECT regions. We conclude that IMP SPECT is useful to identify the epileptic changes and to differentiate the epileptogenic foci from the electrophysiological propagated areas in patients with TS. However, regarding the severity of epilepsy, the MRI findings showed a better correlation than IMP SPECT findings did.

PO-3L1-23 M. Tondeur, R. Denays, A. Piepsz, P. No61,H. Ham. H6pital Saint-Pierre, Brussels, BELGIUM. DETECTION OF BILATERAL AND SYMMETRICAL ANOMALIES IN Te-99m HMPAO BRAIN SPECT STUDIES. Interpretationof Tc-99m HMPAO brain SPECT, based upon the comparison of tracer uptake in left and right hemispheres, doesn't allow to diagnose bilateral and symmetrical anomalies as it needs the knowledgeof the normal anteroposterior distribution. This is not yet available and quite difficult to obtain as it requires a very large number of healthy volunteers of the different agegroups includingchildren. Forthese reasonswetriedtoapproximatethe range of normal values using patients' data. Then, based on the results obtained we investigated its clinical value. We retrospectively selected 205 patients, aged a few days to 92 years, who had a low probability of cerebral lesion. For these patients, whose SPECT didn't show right to left regional asymmetry, we measured, on sagittal slices, activities of cerebellum and several cortical areas and determined multiple cortico/ocoipital indexes and cerebellum/mean cortical index. The results indicated that for all indexes, in each age group, there was an important interindividual variation. Moreover, important modifications of regional perfusionwereobservedduringthefirstyearoflife. Between 1 and 15years, relative increase (compared to occipital activity) was observed till the age of 10-15 years in the prefrontal cortex and till the age of 5-10 years in temporal cortex. After 15 or 20 years, there was a slight decline of cortical activity particularly in prefrontal and motor areas. In a second step, we selected 156 other patients who, despite a symmetrical left to right distribution, could not be included in t he"control" group. Using the "normal values", established for each age group, we could detect bilateral and symmetrical anomalies in neurologicallyimpaired neonates (5/15), psychomotor retardation (4/9), spastic cerebral palsy (4/11), chronic alcoholism (10/41), dementia (2/10). On the other hand, bilateral and symmetrical anomalies were rarely observed in epilepsy (1/12), acute cerebrovasculardisorders (2/14), learning disabilities (0/14), memory impairment (0/8), CO poisoning (0/4).

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Tuesday, 3 September 1991

PO-3L1-24 G.Demeurisse, M.Verhas, C.AIs, M.Stegen, P.Martin et A.Capon Brugmann Hospital, Free University of Brussel LANGUAGE DISORDERS ARE RELATED TO REMOTE CORTICAL EFFECTS IN APHASIC STROKE PATIENTS WITH DEEP-SEATED CEREBRAL LESION. A HMPAO Tc99m SPECT STUDY Our purpose was to study the possible correlation between clinical data and remote cortical dysfunction using clinical indexes and cerebral SPECT with HMPAO Tc99m in aphasic stroke patients with a deep-seated CT hemispheric lesion. Sixteen patients, mean age 66,5 y.were studied within 50 days after the onset of s t r o k e . T h r e e clinical indexes w e r e u s e d to assess the s e v e r i t y of language disorders: Ie (verbal expression), Ic (verbal comprehension) and Ig for aphasia as a whole (range 0-100: n o r m a l i t y ) . B y selection of regions of interest three t o m o s c i n t i g r a phic indexes were e s t a b l i s h e d and expressed as cpm/ pixel: TSIl=pathological area/ healthy right cortex, TSI2=left-sided pathological area/left sided hemispheric cortex and TSI3=left/right cortex ratio. On the other hand, the extent of the left-sided pathological area was expressed in % of the ipsilateral cortex surface (LS). ~esults The deep-seated antomical structures more frequently injured were eentrum semi-ovale(94%), internal capsule (81%) and l e n t i c u l a r nucleus (69%).Significant correlations were found between verbal expression disorders (Ie index) and SPECT indexes TSI(p
PO-3L1-25 N. P.L.G. Verhoeff, E.A van Ro.~fen, J. Overweg, H.F. ~eer. u e p a r ~ _ n~s of Nuclear M ~ c i n e ~ Nefiroloqy, Academic Medical Centre, Amsterdam, The ~ e t n e r l ~ , and Paul Scherrer Irstitute, Villigen, Switzerland CENTRAL BENZODIAZEPINE RECEPTOR DENSITY MEASURED WITH 1-123 ICMAZ~2~IIL IN HEALTHY VOLUIvI'~
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C. Wikkels6, A. Larsson, A-C. Berg, M. Bilting, L. Jacobsson and H. Stephensen. Departments of Neurology, Neurosurgery, Clinical Physiology/Nuclear Medicine and Radiophysics, University of G6teborg, Sahlgren Hospital, G6teborg, Sweden. REGIONAL CEREBRAL BLOOD FLOW IN NORMAL PRESSURE HYDROCEPHALUS: DIAGNOSTIC AND PROGNOSTIC ASPECTS Regional cerebral blood flow (rCBF) was measured in 14 patients with normal pressure hydrocephalus (NPH), 10 patients with vascular dementia (VD) and in 10 patients with Alzheimer's disease (AD) by single photon emission tomography using 99m-To hexamethyl-propylenearnineoxime (HM-PAO). Ten age-matched volunteers served as controls. HM-PAO uptake was measured in the frontal, parietal, mesencephalic, caudal, hippocampal grey matter and frontal and parietal white matter and the perfusion values were expressed as cortical/cerebellar or cortical/cortical activity ratios. The NPH patients had decreased flow to mesencephalic, frontal and hippocampal regions as well as frontal and parietal white matter compared to controls. The AD patients had lower rCBF in the parietal regions and a higher frontal/parietal flow ratio than controls, VD and NPH patients. Low frontal flow and low frontal/parietal flow ratio preoperatively predicted good result of shunt operation measured as improvement in minimental state score. After a ventricular peritoneal shunt operation rCBF increase in mesencephalic, frontal grey and white matter and hippocampal regions. The increase in the hippocampal regions correlated with improvement in psychiatric symptomatology, while the increase in frontal grey and white matter correlated to improvement in the psychometric test score.

ADVANTAGES OF PK-11195, PERIPHERAL BENZODIAZEPINE ANTAGONIST AS TUMOR MARKER FOR DIAGNOSIS AND THERAPY IN GLIOMAS Y.L. Yamamoto, A. Takada, M. Diksic Montreal Neurological Institute, McGill University, Canada

616

Metabolic markers have been used for detection of brain tumors which resulted in 12 to I4 times higher uptake in brain tumors than the normal brain (1~2). However, recent studies indicate that abundant peripheral benzodiazeplne receptors (PBR) are present in the gliomas, but almost none in the normal brain tissue. We have examined PBR density (Bmax) with in vitro P K - I I I 9 5 binding in experimental brain tumors with 10 different concentrations of (3H)-PK-III95 using Scatchard plot. The results of this study are as follows: Bma x (pmol/mg/tissue) in the normal brain cortex (n=5) is 0.15~_ 0.03 (mean:l: SE), Bma x in the AA ascites sarcoma (n=6) is [.39~;0.1J which is 9.3 times higher than the normal cortex (p<0.05). Bmax in the C6 glioma (n=7) is 4.5~0.76 which is 30 times higher than the normal cortex (p (0.05). There is also a significant difference in Bma x between glioma and non-glioma (p< 0.05). This result implies also superiority of P K - I I I 9 B as tumor marker as compared to metabolic markers. Recent study indicates that PBR's are located in the mitochondrla in the tumor ceils (3). Thus, PK-11195 would be suitable for not only diagnostic purposes, but also therapeutic aim, such as neutron capture therapy.

References: I. Tsurumi Y~ Kameyama M, Ishiwata K, Katakura R, Nomura M, Ido T, Suzuki 3: 18F-fluoro-2-deoxyuridine as a tracer of nuclei acid metabolism [n brain tumors. 3 Neurosurg 72:110-1 I3, (1989). 2. Kirikae M, Diksic M, Yamamoto YL: Quantitative measurements of regional glucose utilization and rate of valine incorporation into brain protein by double-tracer autoradiography. 3CBF & Metab 9:g7-95, (1989). 3. Hirsch 3D, Beyer CF, Malkowitz L, Bear 5, Blume A3. Mitochondrial benzodiazepine receptors mediate inhibition of mitochondrial respiratory control. Molecular Pharmacol 3#:I57-163. (198g/.

Tuesday, 3 September 1991

PO-3L1-28

PO-3L1-29

D. C. Yang, M. Huang, M. Girgis, V. Velamati, T. Sezhiyan, and J. Giovanniello. The M e t h o d i s t Hospital of Brooklyn, N.Y., U.S.A.

Irene VirgoZini, M.Banyai, P.AngeZberger, Ursula Barnas, H.Graf, H.Sinzinger. A t h e r o s c l e r o s i s R e s e a r c h G r o u p (ASF) V i e n n a , and D e p a r t m e n t of N u c l e a r Medicine, U n i v e r s i t y of vienna, Austria.

C E R E B R A L AND M Y O C A R D I A L P E R F U S I O N IMAGING WITH T c - 9 9 m HM-PAO - AN INITIAL REPORT. The brain p e r f u s i o n agent - Tc'-99m HM-PAO (PAO) also has high c o n c e n t r a t i o n in the myocardium. To d e t e r m i n e the p o s s i b i l i t y of using PAO to e v a l u a t e both the brain and m y o c a r d i a l perfusion, f o l l o w i n g an I.V. i n j e c t i o n of PAO, S P E C T images of brain and heart were o b t a i n e d for 50 pts (18 M, 32 F, ages 25-92, mean 70), r e f e r r e d for brain p e r f u s i o n study. F o r t y - f o u r out of 50 cases, the q u a l i t y of PAO m y o c a r d i a l images was e q u i v a l e n t to or better than t h a l l i u m (TI) images. Image q u a l i t y of the r e m a i n i n g c a s e s was diagnostic, but not as good as t h a l l i u m images, m a i n l y due to high b a c k g r o u n d a c t i v i t i e s from the lungs. R e s u l t s were c o r r e l a t e d with EKG, history, M U G A and/or T1 stans, 24 cases were true negative; 16 were true p o s i t i v e for MI. In two cases, EKG showed old MI, but PAO images were negative. Right cases showed d i m i n i s h e d p e r f u s i o n in i n f e r i o r wall, which could be due to d i a p h r a g m a t i c a t t e n u a t i o n or MI. Data was not a v a i l a b l e for c o n f i r m a t i o n in these 8 cases. T w e n t y - s i x out of 50 pts have p e r f u s i o n a b n o r m a l i t i e s in both brain and

myocardium. We c o n c l u d e d that a single I.V. i n j e c t i o n of PA0 can be used to e v a l u a t e both c e r e b r a l and myocardial perfusion. High i n c i d e n c e of c o e x i s t i n g c o r o n a r y and c e r e b r a l a r t e r i a l d i s e a s e makes the s i m u l t a n e o u s e v a l u a t i o n of brain and heart desirable.

123I-REOOMBINANT TISSUE TYPE PLASMINOGEN ACTIVATOR (123I-rt-PA)-SCINTIGRAPHY R e c o m b i n a n t t i s s u e type p l a s m i n o g e n a c t i v a t o r (rt-PA) w a s l a b e l l e d w i t h 123I u s i n g I o d o g e n followed by purifation via sepharose gel chromatography. The. r a d i o c h e m i c a l y i e l d w a s 92%, in v i t r o s t a b i l i t y of the r a d i o l a b e l l e d p r o d u c t e x t e n d e d t h r o u g h 12 hours. The b i n d i n g of 123I-rt-PA to washed human platelets i n d i c a t e d h i g h a f f i n i t y b i n d i n g sites, s p e c i f i c b i n d i n g a m o u n t e d to o v e r 90%. P a t i e n t s g o t i n j e c t i o n of 1 m C i / l m g 123I-rt-PA. S e q u e n t i a l i m a g e s (i frame/s) w e r e r e c o r d e d for 30 m i n u t e s o v e r t h e l o w e r leg v e i n s or a r t e r i o - v e n o u s s h u n t area, and a l t e r n a t i v e l y o v e r the l i v e r a n d p r e c o r d i a l area. Late s t a t i c i m a g i n g w a s d o n e for 5 minutes. W i t h i n the f i r s t m i n u t e s a f t e r i n j e c t i o n ' o f 123I-rt-PA the t r a c e r w a s t r a p p e d e x c l u s i v e l y by t h e liver. A s e a r l y as i0 m i n u t e s a f t e r i n j e c t i o n v i s i b l e u p t a k e of t h e t r a c e r w a s f o u n d in v e n o u s t h r o m b o t i c areas. 123I-rt-PA p r o v i d e d e x c e l l e n t i m a g e s of d e e p v e n o u s t h r o m b o s i s and a r t e r i o - v e n o u s s h u n t o c c l u s i o n . C o n t i n u o u s u p t a k e of the r a d i o l a b e l w a s m e a s u r e d u n t i l the 24 th h o u r c o n t r o l time. No false positive findings were sofar recorded as m a t c h e d by a n g i o g r a p h y (n=15). T h e s e f i n d i n g s s h o w t h a t 123I-rt-PA m a y be a s u i t a b l e t r a c e r for t h e d e t e c t i o n of v e n o u s t h r o m b o s i s . A c o n t r o l l e d s t u d y and a c o m p a r i s o n t o v e n o g r a p h y is c u r r e n t l y u n d e r way.

PO-3L1-30

PO-3L1-31

FORTUNATO JS,PIHEIRO MJ,MONTEIRO MC, RODRIGUES MA,AMARAL I. (Centro da Fisiologia da Hemostase (INIC) And Dpts of Physiology and Nuclear Medicine. Oporto Medical School. 4200 Porto Portugal.

Grimmel S, B u e l l U*, Reske SN, Dept's Nuclear Medicine, Wuppertal-Barmen and RWTH Aachen, Germany

LIDOCAINE INHIBITES PLATELET AGGREGATION AND REVERSES

BONE AND BONE MARROW SCINTIGRAPHY OSTEOMYELOFIBROSIS.

IN

1111NDIUM PLATELET KINETIC CHANGES INDUCED BY ADRENALI-

NE "IN VlVO". Lidocaine and other local anesthetics can inhibit platelet (Pit) aggregation "in vitro". However threshold concentrations to display such effect would not be clinically tolerable. In 9 dogs previously re-injected with 111Indium (1111n) labelled Plt for allowing Gamma camera dynamic study a clinical dosage of Lidocaine (4 mg/kg) significantly inhibited the adrenaline-induced microaggregate formation and reversed 1111n Plt retention at hepatic and splenic level justifying significant increases of circulating labelled and unlabelled Plt, comparatively to 6 control animals. These data suggest that Lidocaine commonly used for its anti-arrhythmic effect can also have an anti-aggregant effectiveness which can contribute to avoiding or to lessening thrombotic-ischemic events complicating cardiac conditions.

Osteomyelofibrosis (OMF) is c h a r a c t e r i z e d by myelofibrosis, e x t r a m e d u l l a r y m y e l o i d metap l a s i a and o s t e o s c l e r o s i s . Thus t h e bone (BS) and bone marrow scan (MS) p a t t e r n o f 6 patients with osteomyelofibrosis was compare d t o t h a t o f 141 p a t i e n t s (pts) with various m a l i g n a n c i e s . BS and MS were done 4 h r s a f t e r i.v. injection o f 650 + 50 MBq Tc-99m-DPD and 300 + 15 MBq Tc-99m a n t i g r a n u l o c y t e antibodies with-identical LFOV-gamma-cameras as p r e v i o u s l y d e s c r i b e d ( L a n c e t 1989, i i : 2 9 9 ) . OMF was d i a g n o s e d in a l ! pts by bone marrow b i o p s y . F i v e p t s w i t h OMF were u n d e r c o r t i cold or cytostatic t h e r a p y and I p a t i e n t w i t h OMF was w i t h o u t any s p e c i f i c treatment. BS o f a l l p a t i e n t s w i t h OMF had a s u p e r s c a n - l i k e a p p e a r a n c e w i t h i n t e n s e t r a c e r u p t a k e in a x i a l and a p p e n d i c u l a r s k e l e t o n and m i n i m a l kidney activity. MS in 4 p t s w i t h OMF showed c e n t r a l d e p l e t i o n and v i r t u a l l y no marrow activity, in t h e o t h e r 2 marked p e r i p h e r a l bone marrow e x p a n s i o n and i n t e n s e a c t i v i t y in the enlarged spleen. A superscan-like BS in c o m b i n a t i o n w i t h t h e d e s c r i b e d MS p a t t e r n was n e v e r o b s e r v e d in 141 p a t i e n t s w i t h o t h e r m a l i g n a n c i e s . We c o n c ] u d e t h a t OMF is t o be added t o t h e d i f f e r e n t i a l d i a g n o s i s o f a bone s u p e r s c a n . The c o m b i n a t i o n o f a bone s u p e r scan w i t h t h e d e s c r i b e d MS p a t t e r n i s h i g h l y s u g g e s t i v e o f OMF.

617

Tuesday, 3 September 1991

PO-3L1-32

PO-3L1-33

Hesslewood SR_, Hawker RJ, Turner VS, Hitchell SG, and Harding LE. Dudley Road Hospital and the West Midlands Regional Blood Transfusion Centre, Birmingham UK.

H . S i n z i n g e r , Irene Virgolini, P.Pitscha. Dept. of Nuclear Medicine, University of Vienna, and A t h e r o s c l e r o s i s Research Group (ASF) Vienna, Vienna, A u s t r i a

SIMPLIFIED STORAGE OF PLATELET CONCENTRATES

AUTOLOGOUS 111-ln-OXINE MONOCYTE SCINTIGRAPHY Monocytes were isolated after by elutriation c e n t r i u g a t i o n . P r i o r t o i n v o l v e m e n t of p a t i e n t s b a s i c a l in v i t r o l a b e l l i n g s t u d i e s w e r e c a r r i e d o u t s h o w i n g t h a t cell v i a b i l i t y w o u l d not be s i g n i f i c a n t l y a l t e r e d if 108 c e l l s are l a b e l l e d w i t h 15 ~Ci 111In-oxine. A u t o l o g o u s m o n o c y t e s c i n t i g r a p h i e s w e r e p e r f o r m e d in 18 p a t i e n t s with angiographically proven peripheral vascuar d i s e a s e . S e q u e n t i a l i m a g i n g was done d u r i n g t h e f i r s t 20 m i n u t e s (1 f r a m e / 3 0 s) o v e r t h e c a r o t i d or f e m o r a l arteries, and a l t e r n a t i v e l y o v e r heart, liver s p l e e n and lungs. S t a t i c i m a g i n g w a s p e r f o r m e d at 2, 6, 18, 24 and 48 h o u r s a f t e r i n j e c t i o n of a u t o l o g o u s m o n o c y t e s . Blood kinetics varied extremely indicating a late p e a k m a x i m u m b e t w e e n 6 a n d 18 h o u r s a f t e r i n j e c t i o n of a u t o l o g o u s m o n o c y t e s in 11/18 p a t i e n t s . T h e t r a c e r u p t a k e imaged w i t h v i a b l e c e l l s (viability d e g r e e over 95%) w a s p r e d o m i n a n t l y c o n c e n t r a t e d to the spleen; a l o w e r d e g r e e in v i a b i l i t y led to a m a s s i v e t r a p p i n g b y t h e lungs (and liver). In 10 p a t i e n t s h o t s p o t s w e r e i d e n t i f i e d over e i t h e r t h e c a r o t i d or f e m o r a l a r t e r i e s as e a r l y as 24 h o u r s a f t e r r e i n j e c t i o n p r e s e n t i n g a p o s i t i v e v e s s e l image. In t h e s e i0 p a t i e n t s 111In-oxine platelet i m a g i n g w a s o n l y p o s i t i v e in 1 p a t i e n t a n d 1 2 3 I - L D L - i m a g i n g in 5 patients. T h e a p p r o a c h of i m a g i n g m o n o c y t e s , p l a t e l e t s and L D L in one a n d t h e s a m e p a t i e n t m a y o f f e r a n e w w a y to d e t e r m i n e t h e c l i n i c a l stage of a t h e r o s c l e r o s i s .

Nuclear Medicine techniques have been little used in assessing the quality of blood transfusion products. Platelet concentrates (PC) are generally agitated during storage. Using platelet survival studies in volunteers, we have investigated different methods of storage. PC were prepared and stored for 4 days so that adequate gaseous exchange could occur at 22oC ± 2oC with constant agitation manual mixing once every 24 hours or no agitation. PC were labelled with it 11ndium-oxine immediately prior to autologous reinfusion and gamma camera images taken 24 hours post-infusion to show platelet distribution. Spleen to liver ratios were calculated as an indicator of storage damage.

Storage Condition Constant agitation (3) Mixed Every 24 hours (2) No agitation (3)

% Spleen 38 27 48

S/L Ratio 2.0 1.2 2.1

Preliminary results showed no significant differences between the three storage groups with recoveries of 38.6% + 4.5, 37.8% + 4.9 and 32.8% ± 8.7. Multiple hit analysis gave survivals of 184.1 hours ± 33.2, 171..9 hours -+ 44.9 and 163.3 hours -+ 33.7 respectively (mean + sd, n=6). In vitro tests of platelet function were similar. This pilot suggests PC may be stored for 4 days without agitation with no major deleterious effects on in vivo platelet behaviour.

PO-3L1-34

PO-3L1-35

T a d ~ e r I.S.

Barbano F.,Perrone E,,Frusciante V.,Modoni S., Petracca Ciavarella G., Florio F,, Petronelli S., Err±co M. Depts. of Nuclear Medicine, Radiology and Int. Medicine Hospital C.S.S., S. Giovanni Rotondo (Fg), Italia

D e p a r t m e n t of N u c l e a r M e d i c i n e , M e d i c a l faculty, U n i v e r s i t y of S k o p j e

RENAL SCINTIGRAPHIC CAPTOPRIL ARTERIES

One step T c - 9 9 m l a b e l i n g of a u t o l o g o u s platelets

for the i m a g i n g of t h r o m b o s i s .

Stannous diethyldithiocarbamate stannous gentinsic

acid

(DDC) of

(GA) w e r e u s e d for

l a b e l i n g of p l a t e l e t s w i t h T c - 9 9 m in one step a v o i d i n g b i p h a s i c p r e t i n n i n g methods.

DDC and

GA w e r e i n t r o d u c e s b y S a m s o n C.B. et al. (1988) and S u n d e r h a g e n et al. l a b e l i n g w i t ~ Tc-99m. tion of 2-5x108 logous.blood)

(1986)

for g r a n u l o c y t e

In a p l a t e l e t p o p u l a -

(yielded from 25 m l ACD auto-

DDC incorporated

(n=40), G A 2 0 - 5 0 % / d o s e

30-70%/dose

(n=30). A n a l o g o u s

la-

beling using purhophosphate pretinning technique a c c u m u l a t e d

25-80%/dose.

e x a m i n a t i o n at 2-4h,

Scintigraphic

24h a f t e r i.v. a d m i n i -

s t r a t i o n of 300-500 M B q T c - 9 9 m l a b e l e d platelets was a p p l i e d in 12 p a t i e n t s with reactivated

leg t h r o m b o s i s .

(8 DDC,

s c i n t i g r a p h y v i s u a l i z e d the thromb.

618

4GA)

In 6 p a t i e n t s

TEST

IN

MUL.TIPLE RENAL

The aim of this study is to evaluate the role of deconvolution analysis and MTT (mean transit time) parametric imaging in the processing of renal sequential angioscintigraphy in order to detect the presence and to assess the phisiological meaning of multiple arteries. The transfer function has been obtained using Diffy's matrix algorhitm; however the initialheight (IB) has been calculated according to Rutland method. In the last two years 234 patients have been submitted to renal scintigrafic captopril test (RSCT) in our department, 25/234 pts have shown high values of MTT calulated from a curve of the whole renal parenchima and segmental abnormalities of MTT image : 6.0±1.2 min (m±sd). In 15 controls MTT was 4.0±0.8 min; a statistically significant difference was fond comparing controls with our 25 pts by Student T test for unpaired data (p<0.0005). In all cases intravenous or intraarterious DSA has confirmed the exsistence of multiple renal arteries. In 22/25 pts DSA showed significant renal artery stenosis in one or more of multiple renal arteries according to standard arteriografic parameters. However in 3 pts renal artery that supply the district affected in MTT imaging was quite normal. We conclude that RSCT associated to deconvolution analysis and to MTT image is a sensitive tool to detect segmental functional abnormalities and that an emodinamically significant stenosis may occur also without radiologial classical signs.

Tuesday, 3 September 1991

PO-3L1-37

PO-3L1-36 S.Beatovic,

R.Han, E,Jaksic, R.Blagojev~9

Institute of Nuclear Medicine Unive1~ity Clinical Centre, YU-Beograd GLOBAL CLEARANCE INDEX OF IMPAIRED RENAL FUNCTION

A. BERRIOLO, C. TOUZERY, J.M. RIEDINGER, M. TOUBEAU, J.L. PELLETIER, F. BRUNOTTE. Service de M6decine Nucltalre Centre G.-F. Leclerc - 21034 DIJON CEDEX -FRANCE

99mTcMAG-3 IN PATIENTS WITH

It has been proven elsewhere that 99mTc-MAG-3 is suitable renal functional and imaging agent due to its characteristics similar to orthoiodohippurate (OIH). Renal clearance of MAC--3 is lower then OIH because of its higher protein affinity. The aim of this study was to estimate whether global renal clearance index (CI) of MAG-3 could act as an indicator of renal function. The results of CI were compared with tubular extraction rate (T/~) of MAG-3. CI and T/~ were determined according to Bubeck et ai.1987. Briefly, CI was calculated from renal accumulation of MAC--3 between 60. and i00. sec after i.v. injection of 290-370 MBq of 99mTc-MAG-3 according to formula:

CI=INT[(CountsL+CountsR)/Dose+O.O5}*lO]/1OO*body surface. T/~ was determined by single-sample, slope method using the standard solution of labeled [email protected]. CI and T/~ were performed simultaneously in 134 well hydrated patients with varying degrees of global renal function impairment. MAC--3 was labeled a c c o r d i n g t o t h e manufacturers'instructions and injected within I hour of preparation. Highly significant positive correlation was found between the CI and T ~ (*-0.84, IXO.01, y = 2.14+0.88x). Higher degree of relationship was found in low normal and lower regions of the results obtained. These results suggest that determination of MAC--3 CI merits further clinical evaluation as potential parameter of global renal function. Bubeck B . , Brandau W., Eisenhut M., Weidenhammer K., Georgi P.: The Tubular ExtractionRate (T~) of 99mTc-MAG3:A New Quantitative Parameter of Renal Function,NucCompact, 18,260-267,(1987).

ESTIMATION OF 99mTc-MAG3 PLASMA CLEARANCE FROM THE GLOBAL RENAL UPTAKE MEASURED WITH A GAMMACAMERA

Introduction : Previous works have demonstrated a relation between reaal uptake of OIH and Effective Renal Plasma Flow and between renal uptake of DTPA and Glomerular Filtration Rate. The aim of this work was to establish a similar relation between Global Renal Uptake (GRU) of 99mTc-Mercaptoacetyltriglycine (MAG-3) measured by gammacamera and plasma clearance. Patients and methods : After hydration, 69 subjects (15 normal volunteers and 54 patients) were studied for renal function with MAG-3 preparation from a commercial kit at a dose of 1.33 MBq/kg of weight. The plasma clearance was calculated by Blaufox method with the use of two blood samples withdrawn at 20 and 30 rain while the GRU was evaluated by Gates method. This later method calculates the second minute kidney uptake corrected for background and depth expressed as a percentage of the injected dose. Results : Normal volunteers had a plasma clearance of 343_+72 ml/mn (mean S.D.) after body surface correction and a GRU of 18.6-+2.6 %. The plasma clearance in our patients was found between 36.5 and 403.6 ml/mn and GRU between 0.9 and 20.4 %. The plasma clearance was plotted against GRU showing a strong correlation (r= 0.942). The error of estimate of the linear regression was 39.1 ml/mn, but the best fit of data was given by a 3rd degree polynomial with an error of estimate of 36.5 ml/mn. Conclusion : the present results demonstrate that the kidney uptake of 99mTe-MAG3 during the second minute is strongly correlated with the plasma clearance and that clearance can be accurately predicted from the measurement of the Global Renal Uptake.

PO-3L1-38

PO-3L1-39

~.V.,Budihna*, M.Mil~inski*, M.Koselj+, H.Malovrh+ *Nuclear Med.Dpt.,+Dpt.of Nephrology,Univ. Clin. Ctr.,Ljubljana

J. Caix, Ch. Baquey, Ph. Vincendeau, J.L. Barat, B. BasseCathalinat, D. D u c a s s o u Service de M4decine Nucl4aire-INSERM-U.306 - Universit4 de Bordeaux II - Bordeaux - France.

ARE PARENCHYMAL DEFECTS IN KIDNEY TRANSPLANTS DETECTED WITH 99mTc-DMSA RELATED TO ALOGRAFT REJECTION ?

The a i m o f t h e s t u d y w a s t o e v a l u a t e the renal parenchymal scanning in follow-up of patients with renal transplants. Because of its high sensitivity for detection of parenchymal scars and p e r i t u b u l a r edema we h a v e c h o s e n 99mTc-DMSA f o r f o l l o w - u p o f t h e r e n a l transplant. 41 p a t i e n t s , a g e d 23 - 60 y e a r s w e r e studied. 27 were treated with cyclosporin A and a corticosteroid, 14 had immuran in addition to this therapy. The time after transplantation was in average 2.2±1.9 years. 17/40 patients experienced at least one acute rejection episode in the past. 31 pts had irregular distribution of the 99mTc-DMSA in the kidney parenchyma, showing a pattern of multiple striated areas of decreased radioactivity. In 15 (37.5%) kidneys one or more clearly delineated, occasionally wedge shaped, parenchyma] defects were shown on the scans. The observed frequency of parenchymal defects shown on the DMSA scans was significantly higher in pts who suffered acute rejection episodes (10/17 vs. 4/22 pts. Chi square = 18,2, p
B E H A V I O U R OF I N D I U M n l OXINATE L A B E L L E D N E U T R O P H I L S AT T H E I N T E R F A C E OF BLOOD W I T H ARTIFICIAL SURFACES.

In the last decade, considerable interest has been focused on the neutrophils in order to elucidate the mechanisms in which they take place. After labelling with Indium n l oxinate, we have tested their different functions (Flow Cytometry) and their behaviour in different conditions as well experimental as clinical : - towards NHLBI primary reference materials, candidates for the construction of arterial prostheses or catheters. These were inserted as tubular samples in extracorporeal loop surgically built from and to the femoral artery of dogs, -towards various prostheses generally used in patients (aortic prosthesis, hip prosthesis...). This study has shown : the thrombogenic potential of neutrophils, very soon after the contact of flowing blood with artificial materials studied, - t h e a b i l i t y o f n e u t r o p h i l s to m o b i l i z e a n d t o b e t h e f i r s t to a r r i v e a t s i t e s o f i n f e c t i o n . Taking into account these two phenomena could explain false positive results observed in clinical situations.

619

Tuesday, 3 September 1991

PO-3L1-40 P. Antonacci*, G. Castellano*, G. Ceppi*, M. Falloni*, F. Maranetto*, V. Podio*, T. Spandonari °, G.L. Turco* *Cattedra di M~licina Nueleare - Universit& di Totino (Italy) °Servizio di Fisica Sanitaria - U.S.S.L. TO-VIII - Torino (Italy)

Various Techniques of ERPF Estimation in Kidney-Transplanted Patients Quantitative assessment of renal function and its evolution after kidney transplant is useful to manage the patient. Multiple-sample method with the use of a two-compartment model is the choice for ERPF assessment. Unfortunately, this technique is of difficult use in the common clinical practice. Many studies were already published about the determination of ERPF with two-sample technique and single-sample methods. We performed 14 investigations in kidney-transplanted patients with the impulsive injection of 400-700 kBq of 1251-Hippuran. Blood samples were drawn at 5, 10, 15, 20, 30, 40, 44 and 60 minutes post injection. ERPF was determined with a two-compartment model (multiple-sample method), a one-compartment model (two-sample technique) and with Tauxe's (1982) parabolic and exponential regression equations (singlesample methods); ERPF calculated with the two-compartment model was considered as gold standard. Slope and intercept of the regression equations for obtained clearances, calculated with the three techniques and plotted vs the reference method are reported in the table below toghether with the correlation coefficients. technique single-sample (parabolic) single-sample (exponential) two-sample

slope 0.81 0.83 1.17

intercept 31 27 -14

r 0.96 0.96 0.99

The overall correlation was very good, but the two-sample method gives the best value for intercept, allowing a better fitting for low ERPF value. Only one kideny is implanted during transpantation: this fact and various post-transplant events generally reduce ERPF. In our opinion, ERPF reduction and the ease of execution (for instance sampling times are possible over a fairly wide range) suggest the use of the two-sample technique, at least until a better equation for single-sample ERPF estimation will not be determined.

PO-3L1-41

PO-3L1-42

R.A:M.J. Claessen% A.R. Zandberg, J.D.M. de Vries, L.A.H. Monnens, and F.H.M. Corstens. University Hospital, departments of Nuclear Medicine, Pediatric Urology, and Pediatrics, Nijmegen, The Netherlands.

P.S.Cos~riff, H. Brown Medical Physics Dept, Pilgrim Hospital, Boston

SCINTIGRAPHY OF RENAL TRANSPLANTS IN CHILDREN WITH Tc-99m-MAG3

ANAIaTIC~L ~

We evaluated renal transplant scintigraphy with Te-99m-MAG3 in 40 studies in 22 patients (age: 4-17, l0 yr). No baseline studies were performed and transplant scintigraphy was not repeated regularly. After hydration and emptying the bladder, the patient was placed in supine position under a gamma camera. Tc-99m-MAG3 (dose adjusted to body weight: 35-150 MBq) was injected intravenously. Images and timeactivity curves of the transplant and the adjacent iliae artery were generated for up to 45 minutes p.i.. The combined results were interpreted qualitatively. If histological examination of the graft could not be performed, we used the outcome of other diagnostic procedures and the clinical follow up for verification. Six scintigraphic patterns could be distinguished in this group of patients. (I) No perfusion of the graft. This was confirmed at transplanteetomy in all 8 cases. (II) Severely reduced perfusion of the transplant (8 studies). In 2 cases there was acute and in 3 cases severe chronic rejection, while in 3 cases a severe renal artery stenosis was found. (III) Relatively normal perfnsion, prolonged cortical retention of activity, no dilation of the renal pelvis, and (almost) no Outflow of urine (14 studies). In 12 cases there was acute tubular necrosis (ATN), in 2 cases mild rejection. (IV) Relatively normal perfusion with delayed outflow ef urine and no dilation of the renal pelvis (3 studies). In 2 cases there was mild rejection; 1 patient was recovering from ATN. (V) A dilated renal pelvis, based on a stenosis of the upper urinary tract, was confirmed by other procedures in all 4 cases. (VI) Three studies were normal. No complications developed within 5 months. Scintigraphy with Tc-99m-MAG3 accurately reflects the graft's condition; it is the method of choice for non-invasive evaluation of renal transplants.

The renal clearance of an injected radiopharmaceutical is inversely proportional to the total area under the associated p ~ disappearance curve. In order to reduce the blood sampling requirement to a minirmaa, simplified methods havs been developed which involve approximating the area under the curve. We have examined the (potentially correctable) systematic errors associated with these simplified methods for both GFR and ERPF estimation.

620

~

~CH~-IQ[ES USED IK~ ~

~

~

~

CLEARANCE

OF GFR AND ~ P F .

After simultaneous injection of Cr51 EDTA and I125 OIH, blood samples were taken at 10,20,30,40,50,60,90,120, 150,180,210 and 240 rains. 10 patient studies were analysed. For GFR, the commonly used single exponential (SE) method was cfmpared to a reference bi-exponential (BE) approach and, for ERPF, the standard biexponential method was c~pared to a reference triexponential (TE) technique. The SE metbx~ was found to overestimate GFR by 7-10% (ave 8%) in the range 50-120ml/min, while the BE method overestimated ERPF by 4-15% (ave 8%) in the range 2001000ml/min. No correlation was found between the error and the level of renal function. It is recommended that, as a first order correction, a simple multiplying factor of 0.92 be applied when using the above simplified methods for GFR or ERPF estimation.

Tuesday, 3 September 1991

PO-3L1-43

PO-3L1-44

Y.COTTIN, P~MORELON, C.BAIETTO, F . . ~ D R E , C TOUZERY, J M CHALOPIN, F ~ U N O T T E S ~ r v i c e de H e d e c i n e N u c l e a i r e , C e n < ~ e ] , e c ] e ~ c c . H . u Dijon, FRANCE.

A.Debrand-Passard G. Barzen, J.Hierholzer, W.Richter R.Felix; Department of Nuc, Med. Universit~tsklinikum Rudodf-Virehow (Chbg,) der FUB Berlin, Spandauerdamm 130, W-1000 Berlin 19,

OF THALLI~'[ D I P Y R I O A M O L E IMAGING T O P R E D I C T C A R D I A C EVENTS IN P A T I E N T S WITH C H R O N I C R E N A L FAILURE. W e s t u d i e d 21 c o n s e c u t i v e a s ~ p ~ _ Q n m < i c patients in d i a l y s i s (age 50 2 ~ 6 years) w a i t i n g for t r a n s p l a n t a t i o n They u n d e r w e n t T h a l l i u m D i p y r i d a m o l e S P E C T imaging w i t h a visual a n a l y s i s and 2 D / T M e c h o c a r d i o g r a p h y ( E ) In 8 p a t i e n t s scan was n o r m a l ( g r o u p A ) In 12 p a t i e n t s s c a n e x h i b i t e d a defect in the inferior w a l l w i t h o u t r e d i s t r i b u t i o n and in one the scan sohowed a lateral r e v e r s i b l e d e f e c t ( g r o u p B ) In g r o u p A: E s h o w e d 7 pts without h y p e r t r o p h i c cardiopathy(posterior wall less then 11 n ~ ) In g r o u p B: we found 9 cardiac h y p e r t r o p h i e s (CH) a n d only 4 pts w i t h o u t C H As a c o n s e q u e n c e 90% of the pts with CH had a abnormal scan, and only 36% of the pts without CH: P<0 05 The average duration o f t h e follow u p is 20 ± 5 month (6 to ~5 month) and no c a r d i a c event has been reported i n these 21 p a t i e n t s 10 h a d a k i d n e y g r a f t e d w i t h o u t any cardiac e v e n t : i n this g r o u p the m e a n d u r a t i o n of t h e f o l l 0 w - u p is now 8 , 3 ±3 m o n t h ( 6 to 24). A s y m t o m a t i c p a t i e n t s in d i a l y s i s have a low rate of event i n d e p e n d e n t l y on the a b n o r m a l i t i e s f o u n d a t the T h a l l i u m s c a n M o r e o v e r these a b n o r m a l i t i e s are s t r o n g l y r e l a t e d to c a r d i a c h y p e r t r o p h y in this p a r t i c u l a r g r o u p of patients We c o n c l u d e that D i p y r i d a m o l e T h a l l i u m scan c a n n o t be a d v o c a t e d as a v a l i d m e a n to predict coronary events in a s y m t o m a t i c p a t i e n t s in LIMITATIONS

VALUE OF THE PARAMETRIC EXAMINATION OF RENAL FUNCTION WITH 99m-Tc-Mag3 IN INSUFFICIENT KIDNEYS The most striking advantage of 99m-Tc-Ymg3 against 131J-Hippuran is the better morphological resolution of the gained images, The aim of the study was to investigate the possibility of examination renal impairment and correlate with creatinine, We investigated 160 patients with diabetic nephropathy (n=33), obstructive uropathy (n=22), renal artery stenosis (n=20), kidney cancer (n=17) and others. Results: In correlation with increased craatiniae level, there are typical morphological findings in the scintigraphy. The kidneys are smaller and no intrarenal structures are visible. Simultaneous the time-activity-curves over the kidneys showed a prolonged decrease. The percentual decrease (Excretionsiadex, EI) of the curves between maximum and level at the 25. minute is a good measure of renal function and correlate with creatinine. Conclusions: Scintigraphy with 99m-Tc-Mag3 in patients with insufficient renal function shows reproducible morphological findings. Also it is possible to estimate the claarence without plasma samples by calculation the Exeretionsiadex.

dialysis

PO-3L1-45

PO-3L1-46

E Delcourt, J-P Sinon, R Amir

~2~_mrs_~_~h~[!,Hasheminejhad

C.H.U.A. VESALE

transplantation

6110 Montigny le Tilleul, BELGIUM

A N O B J E C T I V E A P P R O A C H OF B A C K G R O U N D R O I S FOR MAG3 FRACTIONAL CLEARANCES CALCULATION

SELECTION

T w o m a i n p o t e n t i a l s o u r c e s of e r r o r s on f r a c t i o n a l clearances (FCs) calculated from MAG3 renal studies r e m a i n the choice of the background areas (BKGROIs) and the depth a t t e n u a t i o n correction. The p u r p o s e of our study was to select the most appropriate EKGROIs for the slope m e t h o d of FCs c a l c u l a t i o n . In this m e t h o d , FCs are p r o p o r t i o n a l to the slopes of the d i s t r i b u t i o n v o l u m e s of the t r a c e r in each kidney, w h i c h are the r a t i o s of the b a c k g r o u n d - c o r r e c t e d renal curves divided by the plasma curve. T h i r t y - s e v e n u n s e l e c t e d p a t i e n t s were i n c l u d e d in t h e study. P a t i e n t s w i t h e v i d e n c e of o b s t r u c t i v e disease, or with a creatinine clearance less than 30 m l / m i n were e x c l u d e d o w i n g to a p o s s i b l e r e s i d u a l MAG3 activity or a poor uptake and quality images in the DMSA study. After completion of the MAG3 study, DMSA was injected and a SPECT study was p e r f o r m e d 6 hours later. Five different BKGROIS were t e s t e d for FCs calculations: two suprarenal, subrenal, perirenal, or external ROIs, and one interrenal ROI. The renal depth was c a l c u l a t e d from T ~ n n e s e n formula. Since the kidney counts in t h e S P E C T reconstruction images are proportional to the k i d n e y clearances while being u n a f f e c t e d by renal depth and b a c k g r o u n d , D M S A t o m o s c i n t i g r a p h y was t a k e n as the r e f e r e n c e FCs calculation method. RESULTS MAG3 results consider the a v e r a g e d i f f e r e n c e w i t h the r e f e r e n c e FC (DIF), a n d the s t a n d a r d error on the estimate (SEE) of FC on the left side. BKGROI DIF SEE Suprarenal 2.28 5.36

Subrenal

.98 i. 49 .69 .49

Perirenal

External Interrenal

8.71 5.43 4.64 5.89

We conclude that there is a trend for the MAG3 study to o v e r e s t i m a t e the left renal clearance with suprarenal

Kidney

Center,Tehran,IRAN.

D A I G N O S T I C E F F I C A C Y OF TC 9 9 m , D T P A S T U D Y IN E V A L U A T I O N OF R E N A L T R A N S P L A N T S . 430 renal t r a n s p l a n t s institution transplanted

are p e r f o r m e d

in our

since 1 9 8 6 . D u r i n g this p e r i o d , 3 0 6 Pt,s are r e f e r r e d to o u r D p t . A

t o t a l of 775 s t u d i e s are c a r r i e d out u s i n g Tc 9 9 m , D T P A . O f

these cases,171(55.88%)

been normal.Parenchymal in 101 c a s e s ( 3 3 . 0 % )

complication

27 of t h e m are t h o u g h t to

be due to A T N and the r e m a i n d e r rejection. O b s t r u c t i v e

74 due to

complication

i0 c a s e s ( 3 . 2 6 % ) , l e a k a g e

is n o t e d in

in 17(5.55%)

oma in 2 P t , s ( 0 . 6 5 % ) . V a s c u l a r seen in 4(1.30%)

have

is n o t e d

and u r i n -

complication

and l y m p h o c e l e

is

in o n l y one

patient(0.32%). In our e x p e r i e n c e , r a d i o n u c l i d e v e r y e f f e c t i v e and r e l i a b l e

methods

are

in e v a l u a t i o n of

renal t r a n s p l a n t s . O t h e r m o d a l i t i e s

including

s o n o g r a p h y h a v e a d d i t i v e d i a g n o s t i c v a l u e but radionuclide procedures

are i n d i v i d u a l l y

superior.

and perirenal

EKGROIs. Yielding a minimal bias the e x t e r n a l B K G R O I s c o r r e s p o n d e n c e w i t h the r e f e r e n c e

SEE and no s y s t e m a t i c a l gives

the b e t t e r

method.

621

Tuesday, 3 September 1991

PO-3L1-47

PO-3L1-48

T.Erbas,B.Erbas,S.Akalin,E.Varoglu,Z.Koray, O.Ugur,O.Kapucu,C.F.Bekdik.Hacettepe University Nuclear Medicine and E n d o c r i n o l o g y , A n k a r a , T u r k e y

O.Ozdemir,O.Ugur,E.Veroglu,B.Erbas,Z.~orey, C.F.Bekdik,G.Erbengi,E.Orsm. Hacettpps University,Dspts. of Nuclea~ Medicine and Internal Medicine. Ankara,Turkey.

EVALUATION OF ACUTE RENAL EFFECTS OR ENALAPRIL IN TYPE II DIABETICS USING Tc-99m-DTPA.

ACUTE AND CHRONIC EFFECTS OF FELODIPINE ON RENAL FUNCTION USING Tc-99m-HAG 3.

Acute effects of 20 mg oral enalapril(E) on renal function were investigated in 13 type II diabetics( mean:53 y,6M,7F ).BUN and kreatinine values were in normal range. They have neither retinopathy nor visceral/ peripheral neuropathy Plasma glucose regulation was screened by fruc tosamine (F) values. 9 patients had poor m e t a bolic control and two had minimal proteinuria. Only one had high blood pressure. After i.v. administration of i0 mCi Tc-99m-DTPA sequential images were recorded.Glomerular filt ration rate (GFR),perfusion index(PI),time to max-activity(t max),reno index(RI) values of kidneys were calculated. Scintigraphy was repea ~ e ~ t w o days later after oral administration of 20 mg E.Change in blood pressure was recorded. Angiotensin II(A II),plasma renin activity(PRA) and aldosteron (A) levels were determined using RIA at basal level and 2 hrs~ after E. Changes in blood p r e s s u r e , A II,and RI were not significant.PRA and A had changed, significantly (p
Felodipins(F), a calcium-channel blocker, can be used for treatment of high blood-pressurs. Acute snd chronic effects of F on renal functions were studied in 12 hypertensive patients. Renal scintigraphy was performed at basal level 2 hrs after oral adninistration of 5 mg F s n d four weeks later using 5 mCi Tc-99m-MAG3. Effective renal flow(ERPF) according to Bchlegel method,perfusiom index(pi) according to Hilson's method,T max,T I/2,T 2/3 values were calculated. Plssme levels of Endothelin(E) and Atrial Natriuretic Peptide(ANP) were determinsd by RIA. Basal Acute Chronic ERPF ml/min 561 352 360 T msx min 4.1 3.8 5.5 T I/2 min 6.2 5.8 6.5 T 2/5 ~in 3.6 4.1 4.1 Endothelin 54 57 37 ANP 12 11 9 Endothelin levels were slightly hlgher then normals,but there was no change with F.ANP levels showed decrease, but not significantly. Decrease in blood-pressure of patients after four weeks was statistically signifiosnt(p
PO-3L1-49

PO-3L1-50

Fischer, M. Knop, I., Alexandrakis, E.,

K~FGldes, C.Komora x, V.Weszelits, G.Dabasi

Melchior, H.: St~dt. Kliniken Kassel, Dept.of Nuclear Medicine, Urology and Pathology

Semmelweis U n i v e r s i t y of Medicine, Department or Radiology Budapest, Szent Cy~rgy Hospital, Sz~kesfeh~rv~r / Bungarv

99mTC-ABSORPTION IN CONTINENT ILEAL BLADDER Since 1985 in our department of urology the continent ileal bladder is used as a bladder replacement after radical cystectomy. To create this intra-abdominal urinary reservoir an ileal segment of about 40 cm is used. The continent ileal bladder may store urine for hours and its mucosa reacts with secretion and absorption. The aim of this study was to evaluate the amount of absorption of radiopharmaceuticals used for renal clearance studies. In 16 pat. we instilled about 74 MBq 99mTc-MAG3in a volume of 50 ml via a catheter into the bladder. 4 - 40 months after operation. In 3 of 16 pat. the study was repeated some months later. 2 normal pat. serve R as controlls. Sequential images following M A G 3 - i n s t i l l a t i o n were performed for 1 hour. Blood samples were taken for the same time period in i0 min. intervalls. The amount of absorbed tracer was calculated by counting blood samples (Counts/g blood). Mucosa biopsies were taken for microscopic studies of epithelial transformation. In the early postoperative phase (4-8 weeks) significant concentrations of MAC 3 were observed in the blood, whereas in nearly all patients this amount decreased to normal within 2 years. In conclusion during the early postoperative phase metabolic imbalance may occur by absorption. After adaption of epithelium of the continent ileal bladder absorption of MAG 3 decreased to normal.

622

DETECTION OF R~JE~TION IN RENAL ALLOGRAFTS USING RENAL SCINTIGRAPHY AND DUPLEX SONOGRAPHY Since 1973 more than3000 renal scintigraphies have been carried out in patients after renal transplantation at the Semmelweis University of M e d i c i n e Budapest. 131-I- or 123-I-Orthoiodohippurate /IOH/,99mTcmercaptoacetylglicine" /MAG/3 and 99mTc-DTPA were used for radionuclide studies. Scintigrams were evaluated for allograft perfusion and function. During the duplex sonography /DS/ the re ~ sistive index /RI/ was m e a s u r e d in i00 of the cases. All diagnoses were established by clinical criteria. The aim of the study was to separate the acute and chronic rejection /AR and CR/ from the other forms o~ allograft dysfunctions, including acute tubular necrosis /ATN/, cyclosporine /CSA/ toxicity, u r e t e r a l obstruction or infection.and renal arterial stenosis /RAS/. In AR inspire of the poor perfusion a relative good function, "pseudonormal uptake" and long diffuse cortical accumulation were found. Relatively good perfusion and poor function were observed in ATN. Low uptake w i t h normal clearence from the parenchyma and the pelvis was often detected in CR, RAS and recently in u n c o m p l i c a t e d CSA toxicity as well. Prolongated pelvic retention w i t h normal uptake was usually found in obstruction. The m o s t prom i n e n t specific patterns were detected with OIB combined with DS.

Tuesday, 3 September 1991

PO-3L1-51

PO-3L1-52

GordOn, PJ Anderson, MOrton and K Evans. Hospital for Sick Children, don, U K

J P K e l l e h e r , I Gordon, P G R a n s l e y , a n d ME Snell. Hospital for Sick Children and I n s t i t u t e of C h i l d Health, L o n d o n , E n g l a n d .

TWO GAMMA TECHNIQUES 99m MAG3 CLEARANCE.

FOR

ESTIMATION

Lon-

OF

Tc-

T h e a i m w a s t o a s s e s s t h e a c c u r a c y of u s i n g the gamma camera to obtain absolute values of T c - 9 9 m M A G 3 c l e a r a n c e . Children (n=23) u n d e r w e n t 40 min. g a m m a c a m e r a M A G 3 s t u d i e s and simultaneous multiple blood samples for 50 min. C l e a r a n c e c a l c u l a t e d f r o m a b i e x p o n e n t i a l f i t of t h e m u l t i p l e b l o o d s a m p l e s w a s c o m p a r e d to t h e c l e a r a n c e s as e s t i m a t e d from either a curve generated from the c a r d i a c r e g i o n of i n t e r e s t (ROI) or t h e R O I of t h e t w o k i d n e y s (the u p t a k e method) f r o m t h e g a m m a camera. Comparing the multiple plasma sample technique to the curve from the cardiac ROI, t h e r e w a s g o o d c o r r e l a t i o n (r=0.966) i m m a t e r i a l t h e t i m i n g of t h e b l o o d s a m p l e f o r t h e c a r d i a c curve. C o m p a r i n g t h e m u l t i ple plasma sample technique to the renal u p t a k e m e t h o d the c o r r e l a t i o n w a s p o o r e r (r = .85 - .92 d e p e n d i n g on t h e t i m i n g of t h e blood sample). This study has demonstrated that an e x t e n d e d 40 min. g a m m a c a m e r a a c q u i s i t i o n coupled with a single plasma sample may be used for absolute quantitative renal funct i o n s t u d i e s of T c - 9 9 m MAG3.

D M S A O V E R E S T I M A T E S F U N C T I O N IN T H E O B S T R U C T EDKIDNEY T h i s s t u d y w a s u n d e r t a k e n to c o m p a r e t h e D S F as o b t a i n e d f r o m T c - 9 9 m D M S A a n d T c - 9 9 m D T P A in a p i g m o d e l of c o m p l e t e u n i l a t e r a l a c u t e ureteric obstruction. There was a control group and 3 experim e n t a l g r o u p s of a n i m a l s (n=24). T h e l a t t e r h a d a r i g h t u r e t e r i c l i g a t i o n f o r p e r i o d s of 5, i0 a n d 20 d a y s f o l l o w i n g w h i c h t h e y h a d a ureteroneocystostomy to relieve their obstruction. DSF was assessed using Tc-99m DMSA and Tc-99m DTPA at predetermined intervals during obstruction and for 2 months thereafter. Control animals had a sham operation but were not obstructed and D S F a s s e s s m e n t w a s m a d e at t h e s a m e i n t e r vals. Results show that there was no difference b e t w e e n D S F as a s s e s s e d by D M S A a n d D T P A in controls. The obstructed kidney DSF post ligation was:24 hrs 5 days l0 d a y s 20 days DSF DMSA 40% 34% 13.5% 8.5% DSF DTPA 33% 20% 8.5% 3.5% Following ureteroneocystostomy m e a n D S F for b o t h D M S A and D T P A w e r e e q u a l in a l l g r o u p s . W h i l e T c - 9 9 m D T P A is a g l o m e r u l a r agent T c - 9 9 m D M S A is b o u n d by t h e p r o x i m a l t u b u l a r cell and its handling by the nephron is complex. T h i s s t u d y i n d i c a t e s t h a t in a p i g m o d e l of a c u t e u r i n a r y o b s t r u c t i o n t h e r e a r e significant differences between DSF as a s s e s s e d b y T c - 9 9 m D T P A a n d T c - 9 9 m DMSA.

PO-3L1-53

PO-3L1-54

E.GREMILLET, A.CHAMPAILLER. Centre d'Imagerie Nucl@aire. St-Etienne.FRANCE

Marie P Iturralde and Pieter F Venter Departments of Nuclear Medicine and Obstetrics & Gynaeeology. H F Verwoerd Hospital and the University of Pretoria, Republic of South Africa

SIMPLE DEPTH-CORRECTION FUNCTION ASSESSMENT.

FOR

SPLIT

RENAL

To c o r r e c t k i d n e y s ' d e p t h in r e n o g r a m s , it can be shown that u s i n g an a n t e r i o r (A) a n d a posterior (P) v i e w to o b t a i n c o u n t s in t h e left k i d n e y (LA a n d LP) and the right k i d n e y (RA and RP) r a correction factor k=~(LP.RA)/(RP.LA) can be a p p l i e d to RP v a l u e thus s e t t i n g RK to the same depth than LK. We p e r f o r m e d a p h a n t o m s t u d y to a s s e s s the v a l i d i t y of the method. 5 vials were filled with various amounts of 99m-Tc. They were first i m a g e d d i r e c t l y on the camera to o b t a i n I0 t r u e a c t i v i t y r a t i o s (TR) . Then t h e y w e r e p l a c e d at v a r i o u s depths in a c y l i n d r i c a l p h a n t o m f i l l e d with water, A a n d P views w e r e obtained and corrected ratios (CR) were computed. 2 sets of CRs w e r e o b t a i n e d w i t h 2 sets of depths. TRs r a n g e d f r o m 1.29 to 9.81. Agreement b e t w e e n TR a n d CE was e x c e l l e n t : r=0.998, p<<0.01, n=20. In conclusion, we propose to acquire renograms in a c l a s s i c a l way (30 min, P incidence) with a rotating camera, the patient l y i n g s u p i n e on a t o m o g r a p h i c bed. After acquisition, the g a n t r y is i m m e d i a t e l y r o t a t e d to p l a c e the c a m e r a a n t e r i o r l y a n d a 20 sec image is a c q u i r e d . U s i n g t h i s A v i e w a n d the last P v i e w of the d y n a m i c series, the c o r r e c t i o n factor is c o m p u t e d a n d a p p l i e d to t h e R K curve. In o u r e x p e r i e n c e , this method appears convenient for routine c l i n i c a l use.

RADIONUCLIDE STUDIES OF CILIARY FUNCTION IN INFERTILE SMOKING FEMALES Prompted by results obtained from radioaerosol inhalation lung cinescintigraphy (RALC) in patients with immotile cilia syndrome and defective mucociliary clearance in cigarette smokers associated to sperm motility abnormalities and infertility in males - we postulate that female infertility may also be related to the same ciliotoxic effect taking place in the ciliated epithelium of the Fallopian tubes due to an absorbable systemic factor besides the local effect of smoke in the respiratory tract. This suggestion is supported by the fact that women who smoke are more likely to be infertile than women who do not smoke. Using RALC for pulmonary mucociliary clearance and radionuclide hysterosalpingography (RNHSG) for epitbeliotubal function we studied 20 females undergoing infertility investigations. The g studies were performed 3 days apart shortly before ovulation. Ten infertile habitual smoking females who were persuaded to stop smoking were reexamined 6 months later. Smokers had delayed bronchial mueoeiliary clearance during RALC and slow tubal migration of 99mTo-HAM during RNHSG. After stopping smoking, ciliary function returned to normal in the bronchial and tubal epithelium (2 women later conceived). The group of non-smokers had normal bronchial function and infertility related to other tubal factors. Results obtained from this study show that the ciliotoxic effect of smoke does not only affect local mucocilliary clearance from the respiratory tract, but systemically, it also adversely affects reproductive function. Sperm tails, bronchial and tubal eiliated epithelium have a common structural pattern of internal tubules as well as similar function. The argument against smoking holds true for anyone wishing to reproduce.

623

Tuesday, 3 September 1991

PO-3L1=55

PO-3L1-56

11. T. Kit.apj~l, A.A. Esen, C.F. Bekdik, D. Remzi

Re~[,har ,l ~{~d>.a, ; presprlt

Departments of Nuclear Medicine and Urology, Hacettepe University, 06100, Ankara, q%~rkiye

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99~Tc-PENOGRAII IN NORI~L VOLUNTEERS AND ARTERIOGENIC It~OTE}rf PATIENTS

]D~NTIF]CA]ION OF THE URE:.TRII" P E R I S ] A L S I S BY U S E (]F A ] E M P O R A [ 3 A N D P A S S A N D AN AtIIO-'CORRELATION F: ]L [ E l i In the c o n v e n t i o n a l isotope nephrogram (ING) , uretrJc, p e r i s t a l s i s is, d o e to its l o w C o u n t r a t e c o m p a r e d to the backqrouI~d, n o t detectable. The a i m of o u r w o r k w a s to e v a l u a t e the u s e of s p a r t i a l a n d t e m p o r a l fitt~,rs for d i s t r e m i n a t i o n between siqnal and r]olse. Oy~*amic i m a q e s w e r e a q u i r e d w i t h a m a t r i x s i z e ef 1 2 8 x 1 2 8 p i x e l s w i t h a t e m p o r a l r e s o l u t i o n of {~.b s e n o n d s . R e q i o n s of i n t e r e s t (ROI) w e r e p l a c e d over the tLreters a n d all processinq w a s dol,e in t h e s e R O I s . For the f i r s t s t e p t i m e d~,Dendent c e u r ) t rate variations, not failing iJ~to the w i n d o w of the per i s t ~ i t i c frequen,iy w e r e f i l t e r e d o u t by e m p l o y i n q fast fourier a n a l y s i s . ~ h i s filter a l o n e d i d n o t p r o v i d e a d e q u a t e discremirlatio11. S o as a s e c o n d s t e p w e u s e d a f i t t e r , w h i c h e v a h l a t e s the autocorrelation fumuior* of e a c h p i x e I . A f t e r a p p l i r : a t i o n of b o t h f i l t e r s a p a r a m e t r i c i m a g e , w h i c h s h o w s t h e s e q u e n c e of o n e p e r i s t a l t i c w a v e c o u l d be f o r m e d . A p p l i c a t i o n of t h i s m e t h o d in s e v e r a l c a s e s

in this study ~.sculogenic impotence was e,,~.luated by 99~nTc labelled red blood cells (RBC's) to obtain penogram curves in comparison to nori~.l volunteers. 99~Tc-penogram was performed in 23 normal volkmteers and 7 arteriogenic impotent patients. 20 min after in rive labelling of RBC's with 5 mCi 99~Tc04-, 68 mg of papaverine was administered intracavernously, Scintigrams were obtained at I min/frame prior ar~ after the intracavernous administration of papaverine for i hour,Time activity curves generated from region of interest over the penis were a1~.lyzed before and after papaverine injection. The curves reached a maximum in 3 phases. The first, second ar~ third slops of normals were found to be 2123 ± 294, 632 ± 112, 323 ± 69 (mean ± std error) respectively, which were statistically different from each other (p~ 8.005- 0.05).Three different phases detected on 99~Tc-penogram curves correepor~ed well to the, three physiologic phases of erection. )~en the time activity curves of the normal v o h m t e e r s a~xl the arteriogenio impotent patients were compared, it was observed that the first p ~ s e s of the curves were significantly different from each other (ps 0.005). Our results were in good agreement with those of duplex ultrasonography (r:0.785). In conclusion, 99~Tc-penogram is a nonin~.sive and ~ i i ~ b l e method to e~l,mite the physiology ar~ the pathophysiology of erection.

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PO-3L1-57

PO-3L1=58

L. K o s t a k o g l u , H. Abdel-Dayem, S,D.J.Yeh, C, Caluser S,M. L a r s o n . M e m o r i a l S l o a n - K e t t e r i n g C a n c e r Center, New York, NY, 10021.

Linde~aard MW, Aass N, Bue ES, Theodorsen L, and Foss~ SD. The Norwegian Radium Hospital, Oslo, Norway A S S E S S M E N T OF RENAL FUNCTION. A COMPARISON OF I O H E X O L A N D 1 3 1 1 - H I P P U R A N CLEARANCES, A N D E S T I M A T E D

T H E SIGNIFICANCE OF INCREASED 99M-TC M D P & GA-67 CITRATE R E N A L U P T A K E IN P A T I E N T S (PTS) U N D E R G O I N G

TREATMENT FOR MALIGNANT DISEASE. The p u r p o s e of t h i s s t u d y is to d e t e r m i n e t h e e t i o l o g y of diffuse i n c r e a s e d r e n a l p a r e n c h y m a i u p t a k e o n Ga-67 c i t r a t e & 99m-Tc MDP b o n e s c a n s in pts u n d e r g o i n g c a n c e r t r e a t m e n t w h i c h i n c l u d e s n e p h r o t o x i c d r u g s , The pt m a n a g e m e n t f o r r e n a l c o m p l i c a t i o n s is c r u c i a l a n d m a y v a r y a c c o r d i n g to t h e u n d e r l y i n g cause, We e v a l u a t e d Ga-67 & 99m-Tc MDP s c a n s w i t h c o n c u r r e n t c l i n i c a l a n d l a b o r a t o r y (lab) d a t a i n 27 t r e a t e d c a n c e r pts. Ga-67 s c a n s w e r e done a t 48-72 h r s a n d 99m-Tc MDP b o n e s c a n s w e r e d o n e 'at 3 h r s a f t e r i n j e c t i o n o£ r a d i o t r a c e r . Clinical, lab data, p r e & p o s t - t h e r a p y s c a n s w e r e a v a i l a b l e in all pts. We excluded pus w h o h a d blood t r a n s f u s i o n s due to its k n o w n c a u s e of h i g h r e n a l u p t a k e o n Ga-67 s c a n s All pUs (27) h a d d i f f u s e r e n a l u p t a k e o n b o t h Ga-67 a n d 99m-Tc MDP b o n e s c a n s . 22 p t s w h o w e r e t r e a t e d w i t h nephrotoxic drugs such as Cis-Platinum & aminoglycosides, had bilateral, symmetric, diffuse transient kidney uptake on both scans. This was not associated with increased B U N / c r e a t i n i n levels. In t h i s pt c a t e g o r y , t h e r e n a l u p t a k e subsided u p o n c o m p l e t i o n o f t h e r a p y . 5 pts, n o n e of w h o m r e c e i v e d a n y n e p h r o t o x i c d r u g s h a d p e r s i s t a n t (3 u n i l a t e r a l , 2 b i l a t e r a l ) r e n a l u p t a k e o n b o t h s c a n s due to r e n a I i n f e c t i o n s o r o b s t r u c t i o n , In t h i s g r o u p , B U N / c r e a t i n i n levels w e r e e l e v a t e d in a l l pts, We c o n c l u d e t h a t n o p h r o t o x i c i t y due to n e p h r o t o x i c a n t i b i o t i c s a n d c h e m o t h e r a p y r e g i m e n s is a s s o c i a t e d w i t h b i l a t e r a l , diffuse, t r a n s i e n t r e n a l u p t a k e o n b o t h Ga-67 c i t r a t e a n d 99m-Tc MDP b o n e s c a n s . T h e p e r s i s t e n t r e n a l u p t a k e o n s u b s e q u e n t s c a n s is u s u a l l y due to u r i n a r y t r a c t infections or obstructive uropathy & associated with impairement of renal functions,

624

by

selecting i r l c u r r e c t t traits f o r the f o u r i e r filter, uretric peristalsis (Jan be e v a l u t e d . The technique could also be used in o t h e r ~ ases, where regular peristalt~ c processes could be m o A i t o r ed, like fn Ease of the oesophagus.

CREATININE CLEARANCE IN CANCER PATIENTS. Knowledge of the renal function is important in patients scheduled for potentially nephrotoxie treatment. In 34 patients, glomerular filtration rate (GFR) analysed with the X-ray contrast (iohexol) and fluorescence technique, 131I-Hippuran clearance and estimated creatinine clearance were compared. For Hippuran clearance and GFR, the least square linear regression coefficient was 5.01 ± 0.41 (r=0.91). This value concu~s with the five to one ratio between GFR and renal plasma flow known from normal physiology. When the individual values of Hippuran clearance were divided by 5.01, the mean difference between the methods was 0.4 ± 13.4 ml/min/l.73m 2 (mean ± SD). The lower and upper limits of agreement were -26.7 and 25.9 ml/min/l.73m , respectively.-Comparing creatinine clearance estimated from the serum creatinine level with GFR, t~e correlation coefficient was r=O.S9 and the limits of agreement were -29.4 and 21.6 ml/min/l.73m . These agreement limits are in the same range as those which can be calculated from the data from other studies comparing 99mTc-DTFA and 51Cr-EDTA. The results also demonstrate that an unrealistic impression of consistency may result when two methods of measurements are compared only in terms of the correlation coefficient (r). It seems more useful clinically to know the limits of agreement which are estimates of how much the measurement with one method is likely to differ from that obtained with the other.

Tuesday, 3 September 1991

PO-3L1-59

PO-3L1-60

Moonen M., Aldenborg F.*, Volkmann R. and Granerus G. Department of Clinical Physiology and *Department of Pathology, University of GOteborg, Sahlgren's Hospital, GOteborg, Sweden

N. Pateisky, M. Seifert, Ch. Schatten, M.Barrada, H. Huber, P.Fitzal, G.Wolf I. Univ. Frauenklinik WIEN Spitalgasse 23, A - 1090 WIEN / A U S T R I A

A RENOGRAPHIC SIGN OF VASCULARIZED RENAL TUMORS. Split kidney function can be assessed by two different methods, one involving comparison of the net renal counts in each kidney during the uptake phase and the other comparing the uptake slope of the background corrected renograms. The first method includes the activity in the intrarenal blood volume. The purpose of this study was to evaluate the observed differences between these two methods in patients with renal tumors. Method: Two patient groups were investigated, 29 patients with unilateral renal tumors (mainly hypemephroma) and 20 tumorfree patients with various diagnoses such as hydronephrosis, pyelonephritis or urinary deviation. Gamma camera renography was performed with 9~Tc-DTPA during the 16 minutes following the i.v. injection of the tracer. ROIs were drawn manually to define renal areas (in which kidney tumors were included), whereas background ROIs were automatically defined surrounding each kidney. Split kidney function, presented in per cent of the total kidney function, was assessed by the two methods for the affected kidney in the group of the tumor patients and for the right kidney in the control group, Results: In patients with renal tumors (GFR 6-110 ml/min/1.73m2) the differences between the results obtained by the two methods varied between 2 and 57% (10.0 + 16.4%, mean + SD). In the control group (GFR 24-138 ml/min, 1.73 m2), the results of the two methods on the right kidney differed between 0 and 6% (-0.55 ___ 2.7%, mean + SD). Conclusion: The difference observed when using the two methods for determination of split renal function can be explained by a dispropotion between intrarenal blood activity and parenchymal uptake in kidneys with vascularized tumors compared to kidneys with other renal disorders. This renographic sign can therefore be useful for the detection of renal tumors.

HYSTEROSALPINGOSCINTIGRAPHIE (HSS) USING TC-LABELLED ALBUMINE A COMPLEMENTARY INVESTIIGATION IN DIAGNOSIS OF FEMALE STERILITY While x-ray hysterosalpingography (HSG) using contrast media applicated under pressure gives excellent information about morphological changes, there is no information concerning the function of the fallopian tubes. In contrast HSS imitates the migration of spermatozoa. Following intrauterine application of 6-8 MBq 99~Tc labelled human albumin macroaggregates, static scintigrams are recorded up to 2 hrs. Appearance of activity in the region of the tubes and consequently in the free abdominal cavity indicates a normal tubal function. In 6 out of 20 patients investigated by us HSG and HSS gave divergent results (HSG normal/HSS pathol.), indicating dysfunction of the tubal transport mechanisms most p r o b a b l y b a s e d on mechanical reasons. In a further step it is planned to confirm our p r e l i m i n a r y results b y laparoscopic diagnosis. In our opinion HSS is the only m e t h o d available today which provide serious information concerning the tubal function in the diagnosis of female sterility and is therefore c o m p l e m e n t a r y to conventional HSG.

PO-3L1-61

PO-3L1-62

R~ Paul, K. Aho, J. Bergman, E. Eronen, J. Fors-

G. P i c c a o t t o , A. Sargiotto, R. R o p o l o * , P. C e s a ~ a * ~ E. P u g l i e s e , P,G. De F i l i p p i l Nuclear Med. Dep. - Osp. M o l i n e t t e , T o r i n o • H e a l t h Phys, Dep-Osp. H o l i n e t t e ~ T o r i n o , I t a l y

strDm, M. Haaparanta, A. Helminen, S. Parviainen, O. Solin, M. Ter~s Turku Medical Cyclotron-PET Center, Turku University and Turku University Central Hospital, SF-20520 TURKU, Finland [~aF]-2-FLUORO-2-DEOXY-D-GALACTOSE([~aF]FDGal)FOR RENAL STUDIES WITH PET [18F]FDGal is mainly metabolized in the liver. Still, 10-20 % (in rats) is taken up by the renal cortex. We have incidentally observed that the renal cortex is well identified in PET images and have begun a study to compare [XaF]FDGaI-PET in diabetics with nephropathy with renally healthy subjects. The local ethical committee has approved of the study. Each subject gave written informed consent. The d o s e was 4-7 mCi,lmaging was carried out for 60 - 70 minutes. Arterial blood samples were collected for determination of plasma radioactivity throughout the study and the urine was c o l l e c t e d for 2-24 hours after the injection. Results: 4 healthy volunteers and 8 patients with liver disease with no signs of renal illness were compared with 2 insulin dependent diabetics (IDD) with albt~minuria but not azotemia. No obvious differences in the app e a r a n c e of the renal cortices between controls and IDD were seen. The fractional rate of trapping of the tracer was c a l c u l a t e d by the Patlak g r a p h i c a l method, and was 0.174±0.054 for the controls and 0.241 and 0.250 for the two IDD. The rate of excretion of XaF-radioactivity into the urine was 6.3±1.8 pCi/min Vs. 12.3 and 7.2 pCi/min. Conclusion: Incipient nephropathy appears to cause quantifiable changes in the radiopharmacokinetics of [*aF]FDGal, which may be related to renal hyperperfusion in the early phase of IDD-nephropathy.

THE USE OF 99mTc-HAG3 IN URETERAL PERISTALSIS STUDY BY SPACE-TIME HATRIX The s t u d y of ureteral motility gives an important contribution to evaluate the f u n c t i o n o f renal escretory tract and is used as one criterion for the effectiveness of surgical intervention on i t . We s t u d i e d t h e p e r i s t a l s i s by t h e spacetime matrix approach that is noninvasive, does not interfere with ureter function and is b a s e d upon a r o u t i n e r e n o g r a p h y . In some cases the F o u r i e r a n a l y s i s of the ureteral c u r v e s was a s s o c i a t e d . We p e r f o r m e d the examination on hydrated patient w i t h empty b l a d d e r in p o s t e r i o r view using 2.5 sec/frame. 99mTc-MAG3 was used because of its physica] and pharmacokinetic properties: the tubular" secretion gives a sufficient gradient of activity between the

u r e t e r and t h e b a c k g r o u n d u n d e r p h y s i o l o g i c a l as well as p a t h o l o g i c a l conditions, resulting in an e n h a n c e d v i s u a l i z a t i o n of peristalsis in t h e t i m e - s p a c e m a t r i x . He s t u d i e d 42 p a t i e n t s with neurogenic b l a d d e r and u r e f e r o p e l v i c junction pathology, some of them pre several patients post extracorporeal

and post:operative. Moreover were investigated pre and shock wave lithotripsy.

The u s e o f t h e s p a c e - t i m e m a t r i x with MAC3 gives good i n f o r m a t i o n on u r e t e r a l motility such as direction, frequency and regularity of the peristaltic waves thus permitting an estimate of clinical outcome after surgery or

lithotripsy.

625

Tuesday, 3 S e p t e m b e r 1991

PO-3L1-63 R. Piepenburg, G. Maier, K. Hahn Department of Nuclear Medicine, University of Nainz Hospital, D-6500 Mains, FRG EXPERIENCES WITH 99m-Tc-MAG3 AND CAPTOPRIL IN THE DIAGNOSIS OF RENOVASCULAR HYPERTENSION In patients with suspected renal hypertension, renal function studies using 99m-Tc-MAG3 were performed both with and without captopril. Evaluation including angiographie and further clinical findings was possible in 49 cases. Seintigraphic criteria for the diagnosis of haemodynamieally effective renal artery stenosis (RAS) were distinctly protracted intrarenal NAG3 transport and delayed appearance of the tracer in the renal pelvic system under ACE inhibition. Results:

Seintigraphic findings: Angiographie findings: Clinically NO R A S no HAS HaemodynamicallyeffectiveRAS? RAS Typical finding ......... Uncertain ............... N o evidence .............

6 I

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4

21

16

In all patients with typical scintigraphic findings, and in one case with uncertain MAG3 scan and positive angiography, the diagnosis of renovascular hypertension was confirmed. In six patient§, HA angioplasty was performed with good or moderate clinical success. In one case of fibromuscular dysplasia, angioplasty was not attempted. Contrary to this, in four patients with RAS proved by angiography but regular MAG3 scans, the further clinical investigations and course excluded renovascular hypertension. These results show that renal functional seintigraphy with MAG3 combined with a captopril test is a sensitive and specific method to detect renovascular hypertension, and to discriminate between RAS with or without haemodynamic relevance.

PO-3L1-64 P. Antonacci*, G. Castellano*, M. Falloni*, F. Maranetto*, P. Morello*, V. Podio*, T. Spandonari°, G.L. Turco* "Catt~lra di Medicina Nucleate - Universit~ di Tofino (italy) °Servizio di Fisica Sanitaria - U.S.S.L. T O - W / / - T o d n o (Italy)

MAG3 Clearance and ERPF in Kidney-Transplanted Patients Renal dinamic studies obtained with 99mTc-MAG3 are widely used in the management of kidney-transplanted patients. Since this tracer is subject to tubular secretion, it is to establish if it can be used also to determine quantitatively the evolution of renal function following the transplant. We performed 13 investigations in kidney*transplanted patients: MAG3 (120-150 MBq) and 1251-Hippuran (400-700 kBq) were impulsiveby injected at the same time. Blood samples were drawn during and after imaging; clearance of MAG3 was determined with a two-compartment model (multiple-sample method), a one-compartment model (two-sample technique) and with Russel's (1989) regression equation (single-sample method). Hippuran clearance, i.e. ERPF, calculated with the twocompartment model, was considered as gold standard. Slope and intercept of the linear regression equations for obtained MAG3 clearances, calculated with the three methods and plotted vs ERPF, are reported in the table below together with the correlation coefficients.

technique

slope

intercept

single-sample two-sample 8 samples

0.22 0.43 0,41

37 11 12

0.75 0.94 0.91

Results obtained with MAG3 correlate well with ERPF, except for singlesample technique: probably the equation used to determine MAG3 clearance (Russel) does not give good results on our transplanted patients with impaired ERPF (range 118-305 mYmin). We are quickly increasing the number of investigations to improve the statistic significance of our study, but available data show that only twoand multiple-sample methods are suitable for routine clinical use. This results and the ease of execution suggest the use of the two-sample method, at least until a better equation for single-sample MAG3 clearance estimation will not be determined.

PO-3L1-65

PO-3L1-66

M-Poropat I, T.Ron~evi62, D.Dodig I, M.Skugor I, D.

A. P r i ~ e n t , M. A z i z i , P.F. P l o u i n , P. Corvol, M. Paillard. D e p a r t m e n t of H y p e r t e n s i o n . B r o u s s a i s Hospital. Paris. France.

~uzmanid2 DEPARTMENT OF NUCLEAR MEDICINE AND 2DEPARTMENT OF N~PHROLOGY UNIVERSITY HOSPITAL REBRO ZAGREB THE VALUE OF 99m-Tc-DTPA AND 131-1-OIH IN THE DIAGNOSIS OF RENOVASCULAR HYPERTENSION In 33 hypertensive patints with possible renal artery stenosis (RAS) (20 male and 13 female aged between 17-68 years) renal scintigraphy using deconvolution analysis of renogram with 131-I-hippurate (OIH)and 99m-Tc-DTPA (DTPA) were performed before and 60 min after oral 25 mgm Captopril. All patients were submitted to renal angiography: 21 had unilateral RAS, 4 had bilateral and 8 had no renovascular disease. Postive DTPA Captopril renography was found in Ii patients with RAS and in 9 patients on OIH Captopril renography. In 7 patients both DTPA and OIH Captopril scintigraphy were positive and in 13 DTPA or OIH were positive. In 8 patients with no renovascular disease both Captopril scintigraphy were negative. Results showed that Captopril renal scintigraphy with DTPA have 53% sensitivity,with OIH 43% and both together 62%. In all cases of positive findings on scintigraphic procedures, diagnosis was subsequently confirmed by means of pereutaneos transluminal angioplasty or surgery. Specificity OIH and DTPA Captopril scintigraphic procedures was 100%, we found no false positive findings. DTPA and OIH Captopril seintigraphic procedures both have comparable sensitivity which can be increased if the tests are performed at the same time, as we recommend.

626

CAPTOPRIL-INDUCED RENOGRAPHY CHANGES VERSUS CAPTOPRIL-STIMULATED RENAL VEIN RENINS IN THE D I A G N O S I S OF R E N O V A S C U L A R HYPERTENSION. The purpose was to c o m p a r e captopril-induced renography changes with captopril-stimulated renal vein renins to p r e d i c t curability of renovascular hypertension (RVH) before percutaneous transluminal renal angioplasty (n=16) or s u r g e r y (h=l) in p a t i e n t s (Pts) w i t h severe renal artery stenosis (HAS). P a t i e n t s a n d m e t h o d s : 17 Pts (52±19 years) w i t h uni- (n=ll) or b i l a t e r a l (n=6) a t h e r o m a t o u s (n=ll) or f i b r o m u s c u l a r (n=6) HAS>75% u n d e r w e n t T c 9 9 m D T P A renal scan b e f o r e and one hour after a single oral d o s e of 50 mg c a p t o p r i l (Capto-RS) and a r e n a l vein renin ratio determination a f t e r the s a m e c a p t o p r i l s t i m u l a t i o n (Captm-RVR).For each kidney, a d e c r e a s e of 6% in the p e r c e n t a g e of b i l a t e r a l u p t a k e a n d / o r i n c r e a s e s in peak time (>2 min) and r e t e n t i o n (>20%) a f t e r c a p t o p r i l were c o n s i d e r e d significant ch~nges.A RVR ratio (stenotic /contralateral) > 1.5 was a positive lateralisation i n d e x . B l o o d p r e s s u r e c o n t r o l was b a s e d on the US C o o p e r a t i v e Study for R e n o v a s c u l a r Surgery c r i £ e r i a m o d i f i e d by Geykes. R e s u l t s : RS and R V R were p o s i t i v e in 7/17 (41%) and 13/17 (76%) Pts r e s p e c t i v e l y and concordant in 9/17 ( 5 3 % ) . A f t e r 7.2±1.9 months, 14/17 Pts h a v e been re-evaluated: RHV n Capto-RS Capto-RVR Cured+Improved + 8 4+/45+/3No I m p r o v e m e n t 6 1+/55+/1Correct P r e d i c t i o n 9/14(64%) 6/14(43%) C o n c l u s i o n : In this small series Capto-RS and -RVR have the same weak value in p r e d i c t i n g r e s p o n s e to RAS r e v a s c u l a r i z a t i o n and thus in d i a g n o s i n q RVH.

Tuesday, 3 September 1991

PO-3L1-68

PO-3L1-67 A.C. PROST

(t,'~), F.

RAYMOND

(3),

E.

NOE

(2),

G. DERAY (~), J.C. LEGRAND (2), B i o p h y s i c (1), B i o c h e m i s t r y (2) and N e p h r o l o g y (3), C . H . U . La Piti4 - Salp~tri~re, Paris 13 ~me, France. A N T i D I U R E T I C H O R M O N E IN R E N A L F A I L U R E PATIENTS ON MAINTENANCE HEMODIALYS1S. Patients w i t h end stage renal failure (ESRF) have often been p r e s e n t e d as a b n o r m a l l y r e s p o n d i n g to o s m o t i c s t i m u l i as indicated by abnormal releases o f antidiurotic h o r m o n e ( A D H ) . In n o r m o v o l e m i c d i a l y s i s , A D H p r o d u c t i o n h a s b e e n s h o w n to c o m p e n s a t e f o r the h o r m o n e e l i m i n a t i o n in the ultrafiltrate. In this study, plasma ADH (pADH) concentrations were determined by r a d i o i m m u n o a s s a y f o l l o w i n g ODS silica gel extraction in 8 (4 w o m e n , 4 m e n ) non h y p e r t e n s i v e ESRF patients b e f o r e and after a 4 h o u r s (3 h o u r s 1/2 in o n e case) h e m o d i a l y s i s ( H D ) on C A 2 7 0 (R) ultrafiltration m e m b r a n e . S i g n i f i c a n t i n c r e a s e s in p A D H , p l a s m a p r n t i d e s ( p P r o t . ) and a s i g n i f i c a n t decrease in p l a s m a o s m o l a l i t y ( p O s m ) w e r e observed after the end o f HD. B o d y w e i g h t lost w a s - 2.5 -+ 0.4 kg (NS) and hematocrit (Hr.) g a i n e d 3 + 1% (NS). Results are mean -+ SEM. Patients pADH ( 3 8 - 8 2 yrs) pg/ml Before H D 7.7 + 2.2 After HD 17.8 -+ 8.0 * • p < 0.03 ** p <

pOsm mosmol/kg 312 -+ 2 298 -+ 2 ** 0.01 U-test

pProt. g/l 68 -+ 2 77 -+ 3 *

A p A D H (10.1 + 6.0 p g / m l ) is not correlated to A pOsm (-12 + 2 m o s m / k g ) . Per cent o f blood v o l u m e after HD as indicated by Ht. ratio (0.91 -% 0.03 %) or by pProt. ratio (0.89 + 0.04 %) is s i g n i f i c a n t l y reduced (p < 0.01). The rise in p A D H c o u l d be interpreted as a n o r m a l reaction o f E S R F patients m o m e n t a r i l y f i g h t i n g a g a i n s t a r e d u c t i o n o f their p l a s m a v o l u m e due to a water lost during h e m o d i a l y s i s .

R.PUCH~L;N.T.BAJEN;L,PR~T;~.MORA;J.MARTIN-COMIN Servel de Medlelna Nuclear. Hospital Universltari de Bellvitge.Barcelona.Spain

3 SAMPLES PROCEDURE FOR 99m-To-NAG3 CLEARANCE ClLCULUS The aim of this work was to obtain a method that, by means of 3 blood samples (0-30 min. p.i.) let us to calculate the olearence of 99m-Tc-M~G3 as if it would have been obtained by means of I0 samples (0-60 min. p.l.). 30 normal volunters and 28 patients with renal disease were studied. 2.5 m~i 99m-Tc-M~G-~ and 50 ~Ci of 131-IHlppuran were simultaneously inyected. Blood samples were obtained at 4,7,10,13,17,20,30,40,50 and 60 mins p.i. TER and FPR were calculated using a hiexponential method with all I0 blood samples (TER/FPN: r=0.92). Subsequently, aproxi==ative TER was calculated using only blood samples within 0-30 ==in. Corrections factors were calculated for the eoeficients obtained in order to get similar TER values (in the least square sense) to those obtained wlth the I0 samples method. Results: mean _+ I std (mln-max) 3 samples 3 samples I0 samples uncorrected corrected Normal 373 + 82 253 -+ 56 368 + 82 Volunters (194 - 559) (130 - 409) (189 - 595) ======================================================= Renal 195 _+ 79 139 _+ 50 203 _+ 73 disease (33 - 332) (35 - 217) (51 - 314) No §ignlflcant differences were seen Between TER values obtained with the I0 samples and 3 samples corrected methods. They were also highly correlated (r=0.97 p< 0.001). Corrected and non-corrected TER values were significantly different (p < 0.001) Consequently, the 3 samples corrected method permits the calculation of TER with a clinical accuracy similar to t~e obtained with the 10 samples method.

PO-3L1-69

PO-3L1-70

£ L MOREWI'I, J.M R O C C H I S A N I P AURICHE, F TAMGAC, S KRIEF, P BUCHF-T, C CHARTIER. A MEYRIER C H U BOBIGNY. P ~ I S 13. FI%a~ICE

M. O'Driseoll, M. Critchley & J.M. Bone. Nuclear Medicine Department & Renal Unit, Royal Liverpool Hospital, UK.

VERSUS CT SCAN IN ACUTE PYELONEPHRITIS DIISA TC.99m scintigraphy is known to be valuable to detect parenchymal abnormalities in ....~ ' . - - ~ o In clinical practice . kidney ,.~ i~ still presently the most pertinent Imagizk~ ~=~..~ expioration ~,~, this disease. We compared results of both explorations on 34 female patients (38.7 +19.8 years) suffering from acute pyeionephritis. All ~s-,~~ patients had fever, lumbar pain az~ positive urine culture and w e r e imaged 11.4 !5.8 days by scinti~raphy and 15.5 +10.6 days by CT sca:u without and with contrast =medium after .+_.he infectious onset . Five hours after the injection cf an average of 80 MBq of DMSA TC99m in h~rat.ed ~ s . posterior, 30 ° left and right posterior obliques image were registered , and separate percentage kidney uptake was calculated. Images were reviewed by 5 different observers for scintigraphy a~4 hy 3 cnes for CT scan. We fo~u~ 34/34 positive DMSA images and 17/34 ,ositive CT-scan upon which 22 were bilateral ~,n scintigraphy and 3/17 on CT scan . Upon the 14/i7 ~L,~,~.~,,~ m~ilateral CT scan. 9 were bilateral Gn scintigraphy and 5 were ur~iiat.erai o n the same s i d e Tipt~.~ke ~as found e ~ . i to 23~4.4 in normal kidneys ;ii2 and to i 9 8 ± 6 i in infected ones ]~e conclude that :I) detectability of infectious iesio~is u~as hiqher with scintigraphy ::~Tar~l t~: .TT scan. 2)Uptake of DIfSA Tc99n ~,~s l~:~,~e"- - ! i i!:~f eC[IO~.IS k i d i l e ' V s . ~_,~.,~~ '~ 'T '. c~ . . :,~-.~..u,..~.==p~.~,~"~"~ .. ........ . :"_ ~_.c~.~u~8 7::c~:~:ed a~: au :~ite.'--nablve !~:ag!r~; exploration to :'-='-=~" !~! 5.1:!.tze r!~]F=T-~er!hrlrJ~; DM~A

TC99m

R. Rustom, P. Maltby, H.R. Stockdale, J.S. Grime,

RENAL TUBULAR DEGRADATION OF APROTININ (TRASYLOL) MAN.

IN

The degradation of filtered proteins by the renal tubules may have a pathogenic role in progression to renal failure but has hitherto been difficult to measure in man. We have examined the fate of the polypeptide Aprotinin (Apt ~) (Trasylol), a small

~[{500 Daltons> ca}~?nic peDtide labelled with either ~ T c (40 MBq) or - -I (IMBq) in 30 patients, 9 on haemodialysis, 21 with normal renal function. Chromatography with Sephadex-G-2BM was used to separate labelled Aprotinin (Apt ~) from free isotope in urine and plasma. Pla#~a retention, urinary excretion and kidney imaging ( Tc only) were assessed. Plasma retention was biexponential and compatible with plasma and extracellular compartments in both dialysis patients and those with functioning kidneys. In the dialysis patients renal uptake at 24 hours was less than 10% and hepatic uptake never greater than 10% of the injected dose. In the rest, renal uptake was 16 ~ 3.6% of the dose at 3 hours. 16.4 ~ 5.7% of the dose at 4.5 hours, and 28.1 ~ 8.7% at 24 hours. Activity appeared in the urine promptly and chromatography showed excretion only of isotopic label, with no undegraded Apr ~, demonstrating complete uptake of Apt ~ by tubula~_cells. Copulative urinary excretion . ~m ±~± -. . was slmllar with Te and I. Fractional 99m • ~m degradation (urinary T e ~ b y renal Te uptake) fell • + . , rapidly from 33 ~ 19% per hour at 90 m±nuzes ro + 15 - 6% per hour at 4.5 hours, but more slowly thereafter (10.6 ~ 4% per hour at 24 hours). Conclusion These data suggest the Aprotinin is a reproducible marker for tuOular turnover of small filtered proteins in man.

627

Tuesday, 3 September 1991

PO-3L1-71 R~znar

PO-3L1-72

V., E r b a n J., H u ~ k V., K o n e ~ n ~ ~a~raz~I J. Clinic of N u c l e a r ~ e d i c l n e , U n i v e r s i t y H o s p i t a l Olomoue, C S F R

K.,

Q J A ~ T I T A T I V E ASSESS.v~NT OF B L O O D FLO/; OF R E N A L T R A N S P L A N T AND ITS S I G N I F I C A N C E F O R D I A G N O S I S O F CLII~ICAL S T A T E OF T H E GRAFT. I n o u r s t u d y 42 p a t i e n t s a f t e r t r a n s p l a n t a tion of the kidney were s u b j e c t e d to 126 e x a m i n a t i o n s u s i n g 99mTc - D T P A a p p l i e d i n t r a v e n o u s l y , i n a d d i t i o n to the c o m m o n l y used p e r f u s l o n i n d i c e s a c c o r d i n g to H ~ l s o n and W a s h i d a , o u r m o d i f i c a t i o n of L e a r s m e t h o d was applied. The o b t a i n e d r e s u l t s were c o m p a r e d r e t r o s p e c t i v e l y w i t h c l i n i c a l state of grafts. The v a l u e s are s i g n i f i c a n t f o r d i a g n o s i s p a r t i c u l a r l y of n o r m a l l y f u n c t i o n i n g transp l a n t s and r e j e c t i o n s , but r e m a i n o b s c u r e in t r a n s p l a n t s w i t h aGute t u b u l a r necrosis. H o w e v e r h i g h l y p r o m i ~ & n g are the r e s u l t s for d i f f e r e n t i a l d i a g n o s i s of t r a n s p l a n t s w i t h r e j e c t i o n and t r a n s p l a n t s w i t h c y c l o s p o r i n e toxicity.

I.Uslu. Medicine

THE VALIDATION OF THE FERFUSION INDEX CALCULATION IN RENAL TRANSPLANTS BY USING ROI's OVER ILIAC ARTERIES Measurement Of perfusion after renal transplant surgery is important in determining the success of the procedure. This may be accomplished by using a gamma camera and first pass dynamic data after a bolus iv in3ection of Te-99m DTPA All available quantitative techniques are based on the quantification of the transplant blood flow as a percentage index of the renal parenchymal perfusion, relative to one of the iliac artery or the abdominal aorta. In our department we used to take a region of interest (R0!) over the iliac artery ipsilateral to the transplant in more than 400 examinations. During this practice we have realized that in some cases the perfusion index did not correlate well with the clinical conditions of the patient. Then retrospectively, we reanalyzed those patients by taking another R01 over the iliac artery centralateral to the transplant The results in 120 examinations with the new method were in concordance with clinic more than the former one. To overcome the potential errors in calculation the perfusion index of the renal transplants, that could rise due to the scatter from the kidney or a traumatic effect on the iliac artery after surgery, etc. it is recommended to use the contralateral iliac artery in quantitation as reported by some other authors.

628

PROSPECTIVE IMMUNOSCINTIGRAPHIC STUDY STAGING OF CARCINOMA OF THE BLADDER.

FOR

Aim of this prospective study was to assess the value of immunoscintigraphy (IS) for preoperative staging and follow-up in patients with carcinoma of the bladder. Planar scintigraphy was performed in 13 patients ( i0 men, 3 women, aged 64 +/- 9 years, i0 prior to first surgical intervention, 3 prior to re-surgery) 4 and 24 hrs after i.v. injection of 740 MBq Tc-99m of the monoclonal anti-CEA antibody BW 431/26. Additionally, SPECT of the retroperitoneal/pelvic region was done 24 hrs p.i. while bladder was catheterised. Scintigraphy (concordant reading by two experienced observers) was compared with surgery / histology (also in patients with negative scintigraphy). Overall, 9 primary carcinomas of the bladder were confirmed by surgery. All 9 were localized by scintigraphy (true positive). 3 of them were seen only with SPECT. 12 scintigraphic hot spots could not be confirmed by histology (false positive, 7 in the retroperitoneal area, 2 in the liver). In 1 case, second look surgery confirmed the (true) negative result of the sintigraphy. In all patients, serum CEA values were normal. In conclusion, these prospective results demonstrate a limited value of immunoscintigraphy with this antibody for staging and re-staging of patients with carcinoma of the bladder, Especially specificity has to be improved.

PO-3L1-74

PO-3L1-73 H.B Savman, F.Uzum, I Haeiomeroglu. T.Kapicioglu, I.Urganeioglu I U. Cerrahpasa Medical Faculty, Nuclear Dept , Istanbul, Turkey.

D. Sandrock, G. Z611er, D.L Munz, R.-H. Ringert, D. Emrich Departments of Nuclear Medicine and Urology, Georg August University, Goettingen, Germany

G. La Cava, R. Scia~r&, A. R. Formiconi, Meldolesi. Nuclear Medicine, University Florence. Florence, Italy. SIMULTANEOUS ASSESSMENT EFFECTIVE RENAL PLASMA F I L T R A T I O N RATE

OF FLOW

U. of

SINGLE KIDNEY AND G L O M E R U L A R

We have p r e v i o u s l y v a l i d a t e d a m e t h o d for a s s e s s i n g the single k i d n e y e f f e c t i v e renal p l a s m a flow (ERPF) u s i n g 1-131- or 1 - 1 2 3 - O I H and e x t e r n a l m e a s u r e m e n t s only. U s i n g T c - 9 9 m DTPA the g l o m e r u l a r f i l t r a t i o n rate (GFR) can be estimated. A i m o{ this study was to assess s i m u l t a n e o u s l y b o t h the G F R and ERPF to calculate the f i l t r a t i o n f r a c t i o n (FF). We p e r f o r m e d renal s e q u e n t i a l s c i n t i g r a p h y (RSS) in 217 p a t i e n t s (432 kidneys), age range 17-70, a f f e c t e d b Y m i x e d renal diseases. RSS was p e r f o r m e d a f t e r h a v i n g c o u n t e d the p r e - i n jection syringe; lll M B q of T c - 9 9 m - D T P A were i n j e c t e d and a 5 m i n u t e s RSS was acquired; aft e r w a r d s 18.5 M B q of 1 - 1 3 1 - O I H were i n j e c t e d and a s e c o n d RSS was collected. The ERPF and the GFR w e r e c a l c u l a t e d from the uptake of the t r a c e r s in the first minute. The range of the s i n g l e k i d n e y G F R was 6 - 120 m l / m i n and that of ERPF 21 - 446 ml/min. The linear r e g r e s s i o n of the t w o ' v a l u e s gave the f o l l o w i n g equation: G F R = 0.194 ERPF + 2.2, r = 0.87, p < 0.00001, SEE 8.9 ml/min. The c a l c u l a t e d FF was 0.207 ± 0.05, range 0.I0 - 0.53. In c o n c l u s i o n our m e t h o d seems to a l l o w the s i m u l t a n e o u s e v a l u a t i o n of b o t h single k i d n e y G F R and ERPF and t h e r e f o r e the c a l c u l a t i o n with good accuracy of the FF, an u s e f u l p a r a m e t e r in m a n y renal diseases.

Tuesday, 3 September 1991

PO-3L1-76

PO-3L1-75 Mansur S,M.*, Jehangir M.*, Stathaki S., Papadopoulos M. and C h i o t e l l i s E. * PINSTECH ,Islamabad,Pakistan. Demokritos N.R.C.P.S. ,Radiopharmaceutical Lab. Ag. Paraskevi, A t t i ki, 153 I0 Greece RENAL EXCRETION OF Tc-99m COMPLEXES OF CYSTEAMINE DERIVATIVES. Based on the hypothesis that TcO-Gly sequence struc t u r a l l y resembles to the carbonylglycine moiety of hippuran, ethylenedicysteine, E.C. ( I ) , has been introducedl as an e f f i c i e n t renal agent, trasnported through the tubules. Ligands, characi;erized as [ ( t h i o e t h y l ) a m i n o ] c a r boxylates with the following structure: I I :HSCH2CH2NHCH2COOH I I I :HSCH2CH2N(CH2COOH)2 I : [HSCH2CH2N(CH2CDOH)CH2] 2 were tested f o r t h e i r renal excretion c h a r a c t e r i s t i c s . HPLC was employed f o r determination of radiochemical purity and y i e l d , whereas the l a t t e r was >95%. In comparison to MAG3, a hippuran replacement f o r tubular renal excretion, the complexes were b i o l o g i c a l l y evaluated in mice. Data expressed as % percent of injected dose per organ, demonstrate the d i s t r i b u t i o n of tested complexes in animal tissues-a't 30min post i n j e c t i o n . LIGAND BLOOD LIVER MAG3 0.10 1.80 I 0.41 1.39 II 5.89 8.99 III 3.79 2.22 IV 2.60 3.60

KIDNEYS STOMACH INTESTINE URINE 0.68 0.09 7.40 70.29 1.30 0.10 4.46 61.40 4.45 0.56 18.56 43.67 3.49 0.35 4.73 43.97 2.33 0.62 15.41 45.50

Preliminary experiments in mice, treated with probenecid by o r a l l y administrating a dose of Img/gr shown a depression of kidney's a c t i v i t y of about 30%. The transport mechanism of the above complexes through renal tubules is now under investigation.

PO-3L1-77 B.Zmbova I, M.S.Jovanovid I, D.~ivanovi~-Stakid 2, S.Vladimirov 2

F,

THERAIN,

M. PENEAU, D. DEBRUN,

D@p. N u c l e a r M e d i c i n e § U r o l o g y , C.H.R, O r l e a n s - FRANCE RESULTS OF A FACTORIAL ANALYSIS OF THE SCINTIGRAPHIC DATA CONCERNING AN EVENTUAL VESICOURETERAL REFLUX DURING ACUTE RECURRENT PYELONEPHRITIS. Our study c o v e r e d 30 cases : female p a t i e n t s 20, male 7, c h i l d r e n 3, ages ranged from 7 to 59, a l l a d m i t t e d in u r o l o g i c a l s u r g e r y d e p a r t m e n t w i t h d i a g n o s e d non l i t h i a s i c recurrent acute pyelonephritis. This s t u d y aimed at d i s c o v e r i n g eventuel vesicoureteral r e f l u x (VUR). A l l p a t i e n t s were s u b m i t t e d to i n t r a v e n o u s u r o g r a p h y and i n d i r e c t r a d i o n u c l i d e c y s t o g r a p h y (IRC) using 99 mTc DTPA, This s y s t e m a t i c use of IRC j u s t i f i e s itself by the p h y s i o l o g i c a l and non i n v a s i v e n a t u r e of the t e c h n i q u e , M i c t u r a t i n g c o n t r a s t c y s t o - u r e t h r o g r a p h y (MCU) or endoscopy were a l s o added when i n d i c a t e d f o r a c o m p l e t e assesment. Data IRC c o l l e c t e d on c o n t i n u o u s p r o c e d u r e f o r the 5 min. IRC b e f o r e d u r i n g and a f t e r v o i d i n g were a n a l y s e d by two different manners : r e g i o n s of i n t e r e s t (RGI) method and i t s t i m e a c t i v i t y c u r v e s and the factorial a n a l y s i s of dynamic s t r u c t u r e s (FADS) l o o k i n g f o r 2, 3 or 4 f a c t o r s , 11 p a t i e n t s e x h i b i t e d u r o l o g i c a l cues of a VUR ( c l i n i c a l , radiological and i f n e c e s s a r y by e n d o s c o p y ) . As concerns IRC : 4 VUR were d i s c o v e r e d by ROI method, 8 showed on FADS method, these i n c l u d e the f o r m e r 4 p o s i t i v e r e s u l t s , 2 proved n e g a t i v e on both t e s t s , 1 cannot be e x p l o i t e d because of p a t i e n t m o t i o n . These p r e l i m i n a r y r e s u l t s d e m o n t r a t e the s u p e r i o r i t y of FADS upon ROI method f o r VUR d e t e c t i o n p u r p o s e .

PO-3L1-78 Zorbas,

Y. 3. L, Federenko,

Y. F., and ~aexu,K.A.

iThe Boris Kidrid Institute of Nuclear Sciences Vin~a,2Faculty for Pharmacy,Belgrade,Yugoslavia

Hypokinetic Physiology Lab., European Inst. of Environmental Cybernetics, GR-162 52 Athens, Greece

POTENTIOMETRIC STUDY OF Sn(II)-MERCAPTOACETYLGLICINE (MAG) 3 COMPLEX

ISOTOPE RENOGRAPHY IN EVALUATING RENAL ~JNCTION OF PHYSICALLY HEALTHY MEN UNDER HYPOKINESIA

Optimal conditions for formation of Sn(II)MAG3 complex have been studied by potentiomettic titration method using glass and calomel electrodes. The ionization constant of the ligand-MAG 3 and of the complex formed were evaluated from measurements of the variation of hydrogen ion concentration and quantity of added base. The dissociation and protonization constants of the ligand were calculated by the Schwanzerbach's method and the values obtained are pKI=3.54 and pK2=11.94, respectively at T-294 K and at ionic strenght of p=0.1 NaCIO 4. The complex formation was studied at various Sn/MAG3 ratios, e.g. at 1:5, 1:10, 1:15 and i~0. The stability constant of the complex was evaluated at 1.20 ratio, at which no hydrolisis occures. The stability constants of the complex were calculated by the method of Albert. It was found that Sn(II) forms two types of complexes with MAG 3 for acidic and alkaline media at pH values from 3.1 to 9.8. Values of log Ki=ii.55 and log K2=9.68 were obtained. These values indicate that the complex Sn(II)-MAG 3 is very stable and it can be formed from alkaline media. The results of this study have been used in developing the procedure for preparation of a cold kit from alkaline media in the presence of succinic acid as stabilizer. This cold kit requires large amount of tih compared with the semiinstant MAG3 preparate.

The aim of this study was to determine efficacy of isotope renograpby in evaluating renal function of 12 physically healthy subjects aged 20-24 under 564 days of hypokinesia (HK) and a set of piuysical exercises (PE) with fluid and salt supplementation (FSS). The studies were performed during the prehypokinetic period of 50 days, hypokinetic period of 36L-days and posthypokinetic period of 30 days. For the simulation of the hypokinetic effect all volunteers were kept under an average of 5000 stems per day for 364 days. Prior to the exposure to HK all subjects were on an average of 50.000 steps/day and had a VO 2 max of ~0 ml/Kg body weight. Changes in renal function were determined with the use of isotope renography, and gamma-radiation from 1 5 1 i _ h i p p ~ a n excreted by the kidney measured in three scintilation counters. Renal excretion of electrolytes, renal plasma flow rate, glomerular filtration, osmoregulatory functions of the kidneys'were also calculated. At the initial stages of HK the subjects displaced delayed isotope excretion from the kidneys. At the final stages of HK, incorporation of isotope in the kidneys increased in time while elimination of 151I-hippuran from blood and kidneys decreased. Glomerular filtration rate and kidney blood bflow were increased significantly. Excretion of fluid, and electrolytes was also increased. It was concluded that renal functional changes induced due to increased renal blood flow under hypokinesia.

629

Tuesday, 3 September 1991

PO-3L1-79 N. Avril, E. van de Flierdt, R. Bauer, C. Wagner-Manslau, H.R. Langhammer, H.W. Pabst Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universit&t M0nchen, Deutschland ULTRAFINE AEROSOL TECHNEGAS (Tg) vs. Xe133 IN REGIONAL PULMONARY OBSTRUCTION A combined perfusion and ventilation lung scan is requested in cases of suspected pulmonary obstruction. Probability of disease is high, if there are (segmental) perfusion defects in normally ventilated areas (unmatched defects). Ventilation lung imaging can be performed with noble gases and aerosols; each of these techniques has advantages and disadvantages. First studies with Tg has shown probable underestimation of regional obstruction. The aim of the study was to evaluate the degree of underestimation dependent on the severity of obstruction graded as mild, moderate or severe by means of Xe133 scintigraphy. 26 patients were investigated. When Xe133 showed regional obstruction, Tg scintigraphy additionally was performed. 52 obstructions were recognized with Xe133. Tg showed 7/30 mild, 10/12 moderate and 10/10 severe obstructions as regional defects or decrease of activity. Underestimation of mild obstruction usually has no clinical consequences, but normal distribution of Tg in moderate or severe obstruction can lead to false positive diagnosis of pulmonary embolism. Sensitivity of Tg in moderate and severe regional obstruction was 91%. Nevertheless, in some cases false positve results in the diagnosis of pulmonary embolism may be possible. With Tg no distinction between obstructive and restrictive disorder is possible.

PO-3L1-81 D. Hugio, J-J. Lafitte, J. Rousseau, S. Coequyt, X. Marchandise D6partement de M~decine Nucl6aire et D~partement de Pneumologie, CHU Lille, 59037 LILLE Cedex - FRANCE Diagnostic imaging procedures in radiation injury of lung This study was designed to evaluate accuracy of non invasive imaging technics in the early diagnostic of radiation induced lung lesions. METHODS : 14 patients (61 +__ 5.8 age) had thoracic radiotherapy after lobectomy for bronchic neoplasm. Investigations were realized one month after radiotherapy : - extravascular lung water measurement using Fazio's dilution method with r23I-Iodoantipyrine (37 MBq) as water tracer and ~ T c - H S A (370 MBq) as vascular tracer. Differences between transit times gave regional extravascular lung water / unit blood flew (EVLW/F) and / u. bl. volume (EVLW/V) - ~7Galliam scan performed 3 days after injection (92.5 MBq), - MRI (0.5 T) with 20 mm slice thickness using 2 SE sequences (TR = 3 s, TE = 4 X 28 msec ; TR = 0.5 sec, TE = 28 msec). T1 and T2 values were calculated from data and pulmonary water density from spin density by reference to a CuSO 4 solution (0.45 g/l, 30% H~O, 70% D~O), Results were compared ~vith clinic~d status and CT scan performed in the same time and 6 months later. Control values were obtained from 10 healthy volunteers. RESULTS : E V L W / F and E V L W / V were significantly increased respectively in 19 and 20 lungs / 28. L / R relative variations were similar with control values. L / R relative variations of density and T2 were higher and more dispersed than controls. Pulmonary density was higher than controls in 11 lungs/28. At 6 months, 7/13 patients had radiation induced lung lesions and accuracy of early imaging was as follows : MRI (density) 67Gascan EVLW/V Sensibility 100 66 71 Specificity 82 73 42

630

PO-3L1-80 G.Galli, M. Salvatori, M. Antoni, T . P i r r o n t i * , G. Ventura**, G. Maiuro**, L. Ortona**. i n s t i t u t e of Nuclear Medicine, Radiology* and Infectious Diseases**,Catholic University of Sacred Heart,Rome,ltaly DETECTION OF INFECTIONS IN AIDS PATIENTS WITH 99mTcHUMAN POLICLONAL IMMUNOGLOBULIN {HiG):PRELIMINARY REPORT Seventeen AIDS patients(pts)with proved or suspected infections were studied with 99mTc-HIG. Fourteen pts were studied f o r comparison also with 67Gallium-citrate scan (GS). No pts suffered any major or minor side-effect from the radiopharmaceutical. Six cases were concordant positive, 6 cases concordant negative; in 2 cases discordant results (GS positive and NIG negative) were obtained. Final c l i n i c a l diagnosis concluded f o r Pneumocystis Carinii Pneumonia (PCP) in 6 cases (5 true positive and 1 false negative with both radiopharmaceuticals),2 mycobacteriosis (I GS positive, i GS negative, both HIG negative), 2 lung abscesses (positive with GS,I positive and 1 negative with HIG),I intestinal cryptosporidiosis (positive with HIG,GS not performed),1 sacral osteomyel i t i s (positive with HIG and metilendiphosphonate), 1 cutaneous Kaposi's sarcoma (negative with HIG and 201Tlcloture)and 4 AIDS patients with no active infections (all negative with GS and HIG scan). In conclusion,HIG scan may be an useful tool for the study of infections in AIDS pts,expecially for the PCP. The information content seems similar to that of GS even though GS images are in some cases more evident.

PO-3L1-82 F. S. Vargas, J. C. Meneghetti, C. A. Bushpiegel, Tei×eira, M~ Izaki~

A. Cukier,

L.R.

M. Terra - Filho.

Insti~uto do Cora¢~o - University of S~o Paulo - Brazil

SCINTIGRAPHIC PNEUMOCONIOSIS

EVALUATION

OF

CARBORUNDUM

Silicon carbide (SIC) is known to induce to an intersticial lung disease, called carbo[undum pneumoconiosis. The airn of this study was to determine if scintigraphic studies could help in the early diagnosis of this pneumoconiosis. Gallium lung scan (n = 37) and the determination of the lung clearances of ~mTc-DTPA (n = 31} were obtained in 37 male subjects employed in the manufacturing of silicon carbide. Twenty eight were n o n - s m o k e r s ; 14 had normal chest X rays and in 14 there were small opacities (5 = I / 0 ; 7 = I / I ; I = 2 / I and I = 3 / 3 ) . Nine were smokers; 4 had no chest X - r a y abnormalities and in 5, small opacities (2 = I 1 I ) ; I = I / 2 ; I = 2 / I and I = 2 / 2) were observed. The results were as follows: Chest X - ray Smokers n patients Age (vr) Exposure(vr) 1"67Ga Uptake I 99mTc-DTPA T 1/2 min.

Normal Yes

No

4 39.5 ± 4.6 12.2 ± 5.3 3 (76.0%) 3 (;'5.0%) 26.7 -+ 16.9

14 46.3 ± 9.0 11.5 ± 6.3 9 (64.3%) 6 (42.9%) 54.2 ± 20.3

Pneumoconiosis Yes No 5 45.8 ± 10.2 13.0 ~ 7.0 5 (100.0%) 4 (80.0%) 24.6 +- 14.2

14 45.4 +- 8.7 16.5 ± 7.5 14(100.0%) 6(54.5%) 45.1 ± 12.3

Measurement of pulmonary clearance of ~ m T c - D r P A could not differentiate individuals with carborundum pneumoconiosis from those with normal chest X - rays. However, as gallium lung scan were positive in all subjects with roentgenographic evidences of carborundum pneumoconiosis and in 66.6% of the exposed workers with a normal X - r a y , it could be used in the early detection of this disease.

Tuesday, 3 September 1991

PO-3L1-83

PO-3L1-84

M.V. Knopp, L,G. Strauss, H. 8ischoff*, U. Haberkorn, D. 8ranscheid*, H, Manke*, H. Ostertag, J. Doll, S. Helus, W.J. Lorenz, G. van Kaick DeutschesKrebsforschungszentrum,Institute of Radiologyand Pathophysiology, ThoraxklinikRohrbach;Heidelberg,Germany

M.C.Lea, D.S.Lee, J-K.C~ung, J.S.Lee and C-S.Koh. Seoul National University Hospital, Seoul, Korea

ASSESSMENT OF PLEURAL M E S O T H E L I O M A WITH PET USING F-1 8 DEOXYGLUCOSE The non invasive evaluation of pleural mesothelioma presents a major problem in staging and therapeutic management of this disease even with the use of CT and MRI. Malignant pleural mesothelioma shows significant FDG accumulation. This study was designed to evaluate if FDG PET can be used to detect mesothelioma as well as to monitor a response to non-surgical therapy. A wholebody PET scanner (W8 2048/7) manufactured by Scanditronix with BGO/GSO detectors and a rotating point source for transmission scans were used. The standard procedure consisted of endpoint measurements 50 min. post iv. injection of 440 MBq FDG with emission scans of 15 rain. followed by 5 min. transmission scans. Each patient was studied by CT prior to the PET exam and in appropriate cases by MRI. Ten patients are included in this study. Histology was confirmed in all cases whereas 5 patients were surgically treated. Based on our observations we can conclude: Malignant pleural mesothelioma shows significant uptake PET can delineate the active areas of the mesothelioma The intensity of FDG-uptake correlates with the rate of tumor progression The changes in uptake in follow up studies can be used to monitor response to therapy or tumor progression

SCINTIGRAPHIC N f ~ A S U R I ~ OF THE CHANGES OF PULMONARY VASCUIATURE IN KOREAN HI94ORRHAGIC FEVI~ Hemodynamic alterations affect most of the patients in the early phases of Korean hemorrhagic fever and the peripheral vasculature and the pulmonary vasculature are the two major important parts which are affected with vasculopathy. The purpose of this study is to evaluate the changes of p u ~ n a r y vascular volume and vascular permeability with relation to the disease courses in patients with Korean hemorrhagic fever with radiolabeled albumin cinescintigraphy. We performed lung and heart cinescintigraphy with 99m-Tc ablumin in I0 patients sequentially at every phase of the disease. Density ratio between the regions of interest (mainly compared with the density of the heart) and tidal density ratio changes for the first sixty minutes after the injection of albumin were calculated. Density ratios of lungs to heart and liver to heart rose upto 2.0 and 2.3 respectively in late oligurie or early diuretic phases, and then decreased to normal values of about 0.5 at late phases. And the slopes of tidal changes of density ratios showed the largest positive deflection during or just after hypotensive phase (2.9x10E-2) and then negatively deflected at later period (-3.99x10E-2) for the lungs as well as for the liver. At last, this returned to normal values of near zero. According to scintigraphical evaluation, pulmonary vascular blood volume increased most, late at oliguric phase and pulmonary vascular permeability increased most, at earlier period in patients with Korean hemorrhagic fever.

PO-3L1-85

PO-3L1-86

Y. RIOART;J. MARTIN-OOMIN; D. PODZAMCZER'; L. PRAT; HI. S~A; H. CASTELL and M. RAMOS. Serveis de Hedicina Nuclear and Medicina Interna*. Hospital Universitari de ~ellvitge. Barcelona. Spain.

M,Mysli~ek,V.Hu~k,V.Kolek,J.Erban,V.Kn~pek D e p t . o f N u c l e a r M e d i c i n e , C l i n . o f Respiratory Disease, University Hospital, Palaeky University, O l o m o u o , C z e c h o s l o v a k i a

o*Ga-CITRATE SCANNING IN THE MANGEM~T OF AIDS

QUANTITATIVE

NIBe%y-nine HIV + patients (93 males) were studied. Mean a ~ was 28 years (19-44).A thorax radiography (Rx) and a @7~-cltrate scanning (GA) were done in 120 cases as r ~ t l m e tests. Patients were classified in Groupe I (N= |2): S~owing adenopathies, without fever. Groupe 2 (N= @6): Those having fever and adenopahies and Groupe 3 (N=42): Those having only fever. GA uptake was scored from 0 to 3 compared to liver activity, grades 0 and 1 were considered normal. R e s u l t s : Group 1 GA was negative in 8 cases: 5 AIDS related comples (ARC) and 3 other infections (OI); Rx Wag normal in Ii. GA was positive in 4 cases: 2 lung tuberculosis (TBC), one ARC and I lymphoma; the Rx was pomltive in I TBC and the ARC. Group 2: GA was nornal in 30 cases, 16 ARC, 3 TBC, 2 Kaposi's Sarcoma (KS), 8 0 I and ! ending AIDS ), the Rx was positive in I0 cases 4 lh~O, the TBCs, 2 NLI and the ending AIDS. The scanning was positive in 36 cases:27 TBC, 3 pneumocistis carlnii pneumonia (PCP), 1 ARC, 3 lymphomas and 20I; the Rx was demonstrative in only 13 TBC and 3 PCP. Group 3: GA was normal in 20 cases : 10 ARC, 6 OI and i TBC; Rx was positive in 2 ARC and 2 sepsis. Ga was positive in 22 cases: 12 TBC, 6 POP, i ARC and 3 0 I while Rx was normal in 2 TBC and 1 pop. ~onclussions: Though GA scanning seems more accurate than Rx in the management of AIDS patients,, both thorax radiography and gallium scanning should be performed. If both exams are normal lung complication may be discarded. When both exams are abnormal TBC or POP are highly suspected (they can be differentiated on the basis on tracer distribution). If only the scan is positive ganglionar TBC is the main diagnosis.

67GA

S C I N T I G R A P H Y IN P U L M O N A R Y SARCOIDOSIS A m e t h o d of a b s o l u t e q u a n t i t a t i o n of 6 7 G a a c c m m u l a t i o n in l u n g s w i t h a L F O V c a m e r a a n d computer was employed. The uptake of 67Ga /67GaU / i n l u n g s i n % of a d m i n i s t e r e d r a d i o a c t i v i ty was determined by a transmission-emission method. The method combines the observed count d e n s i t i e s of a n t e r i o r a n d p o s t e r i o r i m a g e s with the attenuation information obtained fro~ a 5 7 0 0 t r a n s m i s s i o n i m a g e . R e g i o n s of i n t e r e s t w e r e d e l i n e a t e d u s i n g 9 9 m T o - M A A scans, The method was applied to control subjects / n = 2 5 / , a n d to p a t i e n t s /n=70/ s u f f e r i n g f r o m biopsy-proved pulmonary sarcoidosis /27 with i n a c t i v e a n d 4 5 w i t h a c t i v e d i s e a s e / . 16 p a tients were examined during 6 month Prednison t r e a t m e n t . R e s u l t s w e r e c o m p a r e d w i t h the v a l u e s of SACE, B A L - l y % and X ray imag~s. 67Ga-U in inactiye disease was 6,65-I,01% / n o r m a l r a n g e ~ , 6 1 z O , 9 1 % / , 6 7 G a - U in a c t i v e d i sease was 9,96~3,@9%. There was higher 67Ga-U in 5 0 % o f p a t i e n t s w i t h X r a y s t a g e I. The res u l t s o f 6 7 G a - U d i d n o t c o r r e l a t e w i t h a n y of the u s e d m e t h o d s . A f t e r t r e a t m e n t the m e a n dec r e a s e w a s 4 5 , 4 % in 6 7 G a - U , 2 2 , 5 % in S A C E a n d 55,5% in BAL-Iy%. The quantitative 67Ga scintigraphy appeared to be a v a l u a b l e t o o l in the m a n a g e m e n t e f p u l m o n a r y s a r c o i d o s i s . It i s a u s e f u l i n d i c a t o r of s a r c o i d o s i s a c t i v i t y , of the c o u r s e of t h e d i s e a s e a n d t h e r a p e u t i c e f f e c t . It considerably reduces reader's bias and interobserver variability.

631

Tuesday, 3 September 1991

PO-3L1-87

PO-3L1-88

M. Pillay, A.S.Th. Planting and P.H. Cox, Or. Daniel den Hoed Cancer Center, Rotterdam. The Netherlands.

O.Rosso*,J. M . G u i l l o n * * , A.Par r o r * * , M. D e n i s * * , G . A k o u n * * CT~d*%M.Meignan*. *H6pital Henr Mender, service de m6decine nuci~aire,Cr~teil,France.** H6pital Tenon, Centre de pneumologie et de r#animation respiratoire,ParJs, France.

THE EFFECT OF SYSTEMIC BLEOMYCZN AOMINISTRATION

ON THE

ALVEOLAR CLEARANCE OF AEROSOLISED To99mHIOA. The therapeutic usa oq blaemyein (an antitumour antibiotic] can be sarioosly hampered by its toxicity to lung tissue. Although the carbon monoxide di~{usion capacity is generally used to determine lung function, its reliability in detecting early bleomycin effects on the lung remain questionable. Many investigators have proposed the use of alternate diagnostic techniques such as al ~ veolar volume, vital capacity, pulmonary capillary blood volume Xe-133 end ToBBm measurements in order to increase the sensitivity. We report the results of a pilot study (I0 patients] who had carbon monoxide diffusion capacity test as well as a To9BmHIOA redioearosol investigation before chemotherapy and 3 months later following a total dose of 380mg bleomyoin, ToBBmHIOA was aeresolisad using a high efficiency ultrasonic nebuliser with an Output of 80% particles <2 m VMAO. The results indicpte that total clearance of To98mHIOA reflect changes as measured by carbon monoxide diffusion [p<0.1]. However, regional changes in the alveolar clearance of the radioaerosol were more-sensitive (p
PO-3L1-89 R. Bauer, E. van de Flierdt. H. Pr&uer, U. StSckle, H.R. Langhammer, H.W. Pabst Nuklearmedizinische und Chirurgische Klinik, Klinikum rechts der Isar, Technische Universit~.tM(Jnchen, Deutschland GATED VENTILATION SCAN WITH Xe127 IN THE ESTIMATION OF RESIDUAL LUNG FUNCTION PRIOR TO LUNG SURGERY Whole body plethysmography and lung perfusion is usually performed prior to lung surgery to determine the postoperative residual function. Additional ventilation scans are helpful in borderline cases to assess distribution of vital capacity (VCb) and intrathoracical gas volume (ITGV) by the single breath and the equilibrium. Gated ventiliation scans (GVS) allow quantification of the regional distribution of the respiratory volume (RDRV) in normal and enforced breathing patients. The aim of the study was to assess the clinical value of this method in comparison with the conventional method. 17 patients with lung tumors (64 + 8 yrs) were studied. Assuming the RDRV to represent the real physiological gas exchange, Vain overestimated the gas exchange of the diseased lung by up to 14%. Distribution of ITGV differed from RDRV by maximum 20%. In conclusion, borderline cases should be investigated both by perfusion scans and by GVS. The comparison of regional perfusion and RDRV enables for correct preoperative estimation of the postoperative functional result. VOin and regional perfusion correlate also with the postoperative result but to a less degree. In addition, Vain is highly dependent on the patient's cooperation. ITGV is no predictor of postoperative function.

632

PULMONARY COMPLICATIONS OF HIV INFECTION.'THE PLACE OF AEROSOL DTPA SCANNING AND GALLIUM CHEST SCAN. We retrospectively compared the results ef Gallium-67 chest scans and technetium-99m DTPA aerosol clearance measuremenLs with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 19 -mainly Pneumocystis Carinii Pneumonia (PCP)- and a noninfectious disorder was found in 42-mainly Kaposi's sarcoma (KS) and lymphocytic alveolitis. Gallium scan and DTPA celarance were abnormal respectively in 72% and 92% of infectious complications, and in 12% and 60% of non infectious disorders. In 10 cases, DTPA clearance was accelerated while chest X-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance ~ 4 . 5 % . m i n was beth sensitive and specific for the diagnosis of PCP. Gallium scan was always normal in case of brenchopulmonary KS. We concluded that, in symptomatic patientstl)DTPA clearance measurement is useful for detecting lung disease when chest Xray and/or PaQ2 are normal,2)Galiium scan is indicated to distinguish progressive KS from a superimposed second process when radioiogieat abnormalities of pulmonary KS are present.

PO-3L1-90 Van der Wall~ H. & Murray, I.P.C. The Department of Nuclear Medicine,

Prince

of

Wales

Hospital, Sydney, Australia. A VENTILATORY TECHNEQAS

ASSISTANCE DEVICE FOR

USE WITH

High quality ventilation imaging in the intubated, poorly cooperative or very young patient has required the advent of a number of ventilatory assistance devices (VAD). These devices have, in generaL, been interposed between the source and patient, leading to increase in the dead space, and variability of flow rates*with frequent central deposition of

aerosols, resulting in inadequate peripheral penetration and degradation of image quality. A VAD was designed and manufactured in co-operation with Tetley Technologies to utilise the superior imaging qualities of Technegas in this group of patients. This device utilises an external supply of a i r at a controlled flow rate to purge the Technegas into the patient with an inspiratory or manual trigger. The flew rate can be ~;aried up to 25 l/min with a maximal delivery pressure of 18 cm H20. As the VAD is located distal to the Technegas generator it does not add to the dead space. Preliminary clinical studies have demonstrated that the device can be employed in a variety of patients and allow the satisfactory administration of Technegas. This group comprised lO'patients ranging in age from 4 weeks to 67 years. It included 2 intubated neonates undergoing assessment for lung transplantation and 2 sedated children aged 2 and 3 years, being studied prior to bone marrow transplantation. The remaining 6 studies were in adults with suspected pulmonary embolism whose condition negated compliance with standard Technegas inhalation. In all these patient% ventilation images retaining the properties of Technegas and permitting diagnostic evaluation, were obtained.

Tuesday, 3 September 1991

PO-3L1-92

PO-3L1-91 C.Villa, R.Zoccola, °L.Mutti N u c l e a r M e d i c i n e S e r v i c e , C i t y H., A l e s s a n d r i a 0 M e d i c i n e D e p t . , C i t y H., C a s a l e M . t o - I T A L Y

99mTc-DTPA Alveolar-Capillary Permeability, TLCO and BAL in Asbestosis We analyzed the lung epithelial permeability (L.E.P.), the Transfert Lung Capacity (TLC0) and the Bronchoalveolaf Lavage (BAL) in 12 non smoker patients with asbestosis and in 7 healthy non smoker volunteers. LEP was measured as half-time clearance of an inhaled aerosol of 99mTc-DTPA (TI/2); TLCO was performed by single breath method. Ii patients with Asbestosis showed a decrease of TI/2 (38.2 +/- I0 min. vs. 64.2 +/- 12 min.; p < 0.05). We observed a decrease of TLCO value in all patients with Asbestosis (64.2 +/- 10% vs. 80 +/- 5%; p (0.05). BAL demonstrated that, on the average, there were more cells recovered from patients with Asbestosis (250 +/- 16xlOG/ml vs. 210 +/- 15xi06/ ml; p < 0.05). On the average, the proportion of neutrophiles was increased in Asbestosis (3.3 +/- 0.4 vs. 2 +/- 0.i; p< 0.05), CDS, CD4 and CD8 ratio were similar in two groups (77 +/- 5 vs. 78 +/- 2; p:n.s.; 1.4 +/- 0.4 vs. 1.5 +/- 0.4; p:n.s.). In patients with Asbestosis the decline of TLCO was indirectly correlated to TI/2 (r=0.5; p < 0.05) and directly correlated with the percentage of BAL neutrophiles (r=0.5S; p < 0.05). CD3, CD4 and CD8 ra~io were not correlated with LEP and TLCO. These data suggest that abnormalities Capillary Permeability and TLCO depend pathogenetic mechanism.

of on

Alveolardifferent

S. ~'~AL, I. ADALET,S. CANTEZ, A. C.~RPE Dept. oT Nuclear Medicine,Istanbul Medical Faculty, Istanbul,Turkey. THE ROLE OF THALLIUM--201 TOTAL BODY SCINTIGRAPHY(TBS) IN D E T E C T I O N OF THYROID CARCINOMA METSTASES(TCM)

The aim of this study is to evaluate the role of Thal-lium-2Ol(Tl) TBS in detection of TCM.The study consisted of 20 patients (12 female,8 male) Who were undergone-(sub) total thyroideetomy for histologically proven TC.The his-tologic type was folicular in lO,papillary in 7,mixt in 2, and anaplastic in 1 patient.40 scans were performed.All the patients had T1 and 1-131(1)TBSs,ehest X -Ray.Thyroid hormones,antibodies,thyroglobulin (Tg),CEA,ealcitonin were assayed.8 patients (pts) had CT examinations and 5pts with mismatching TI and I TRS had biopsy. The Detectability Of TCM: T g + Tg Total T] + T1 T] + T1 1--131 + 2 i 3 0 6 1--131 I 0 3 i0 14 Total 3 1 6 I0 20 TI localized TCM in all pts with +I TBS except one.That pt had histologically proven lymphocytic thymoma,TCM in the lung and high Tg. In four pts with +TI and -I TBS,metastatic loci were shown on CT and proven histologically. The Detectability Of The Remnant Thyroid Tissue: T1 + T1 -Total I-]31 + ii 5 16 1--131 -1 3 4 Total 12 8 20 The TI TBS i s more s e n s i t i v e ( 9 0 ~ ) than both I TBS (66%) and Tg in detection TCM,but less sensitive in visualizin~ the remnant thyroid tissue,the sensitivity being 73.8~ and 94% resnectivelN.

PO-3L1-93

PO-3L1-94

S.K.Shukla I,Z, C.Cipriani~ G.Argir6 1 ,L.Taglia,3 S.Hani 4, K.Schom~cker5,G.S.Limouris6,R.Hermesl; l)Med. Nucl.,Osp. S.Eugenio,Roma; 2)Ist. Cromatografia,CNR,Roma;S)Amb.Vet. (I),Roma; 4)Amb.Vet.(II),Roma;5)Klin. Poliklin. Nuklearmed K~in Univ.,Germany;6)Dep. Nucl.Med.,Athens Univ.,Greece

C- Grimm, R. Montz, J. K n o p D e p a r t m e n t of N u c l e a r M e d i c i n e University Hospital Eppendorf Hamburg, G e r m a n y

TUMOR-SPECIFIC Y-90 SPECIES IN SOLUTION FOR ANIMAL AND HUMAN TUMOR THERAPY For tumor therapy Y-90 citrate complex solutions or Y-90 labeled antibodies have been tried. Due to the presence of tumor-nonspecific species in the above solutions,high toxicity in the Y-90 treated subjects was reported. We analysed the commercially available Y-90 radiopharmaceutioals chromatographically and eleetrophoretieally and found them to contain cationic, neutral, and anionic species, many of which tended to hydrolyse under physiological conditions. Our studies with pure Tc-99m and with Ga-67 had permitted us to classify malignant tumors into two main groups: Cation-affine tumors: thyroid tumor, lung tumor, neuroblastoma, Hodgkin's disease,hepatoma,... anion-affine tumors: breast tumor, melanoma, osteosarooma, Ewing's sarcoma, fibrosareoma, liposarcoma,... Since stable Y-90 anionic species in solution are easier to be prepared, we studied first the antitumor activity of chromatographically and eleetrophoretieally pure anionic Y-90 complex. The tumor uptake of the radionuclide depended mainly on the anionic nature and the stability of the complex, and was not affected by the nature of the anion used to form the complex. Spontaneous mammary tumors inmice, cats, and dogs completely regressed by repeated administration, every third day, of S.7 MBQ/Kg of Y-90. Regression of osteosarooma in animals and humans was also observed with anionic Y-90, Growth of melanoma of a dog was arrested by Y-90.

P I T F A L L S IN 1 3 1 - I O D I N E W H O L E - B O D Y CARCINOMAS

SCANS F O R T H Y R O I D

Since an a b d o m i n a l 1 3 1 - I - u p t a k e in t h e w h o l e - b o d y s c a n of an a t h y r o i d p a t i e n t w i t h d i f f e r e n t i a t e d t h y r o i d c a r c i n o m a s o n o g r a p h i c a l l y r e v e a l e d as a l a r g e r e n a l cyst, we d e c i d e d to c o l l e c t cases c o n c e r n i n g s u c h u n u s u a l l o c a t i o n s of 1 3 1 - I - u p t a k e . Me%hod: P a t i e n t s w i t h t h y r o i d c a r c i n o m a w e r e e x a m i n e d by 131-I w h o l e - b o d y scan. The o c u r r e n c e of u n s p e c i f i c or u n p h y s i o l o g i c a l 1 3 1 - I - u p t a k e was e x p l o r e d b y x-ray, u l t r a s o u n d or d e n t a l e x a m i n a t i o n . Results: A m o n g s t 118 p a t i e n t s w i t h t h y r o i d c a r c i n o m a b e i n g t r e a t e d by 131-I b e t w e e n july and d e c e m b e r 1990 in our d e p a r t m e n t , we found 6 cases w i t h s u c h i r r e g u l a r 131-I-uptake. Unexpected abdominal 131-I-activity was c a u s e d b y a l i v e r cyst in one case, a renal cyst as d e s c r i b e d above and by h y d r o n e p h r o s i s in a f u r t h e r case. A b n o r m a l t h o r a c i c 1 3 1 - I - u p t a k e w a s f o u n d to be due to p l e u r a l f l u i d a f t e r t h o r a c o t o m y . We o b s e v e d an u n p h y s i o l o g i c a l oral 1 3 1 - I - a c t i v i t y in two cases, one due to s a l i v a r y r e t e n t i o n u n d e r a b a d f i t t i n g d e n t a l p r o s t h e s i s , the o t h e r in c a r i o u s teeth. C o n c l u s i o n : L i t e r a t u r e refers to the o c u r r e n c e of 131I - u p t a k e in a s t r u m a evarii (i) and in the m e d i a s t i n u m after esophagogastrostomy due a c h a l a s i e (2). Our o b s e r v a t i o n s also d e s c r i b e u p t a k e in liver or r e n a l cysts, h y d r o n e p h r o s i s , effusion fluid and dental decay. (2)Brandt,K., Wahner, H.-W., JNM 3 1 : 1 9 7 4 ( 1 9 9 0 ) (1)Zwas,S., Heyman,Z., Lieberman,L., Sem. M e d . : X I X : 3 4 0 - 342 (1989)

Nuc.

633

Tuesday, 3 September 1991

PO-3L1-96

PO-3L1-95 D.HOFFSCHIR*,J.C.PITrET**, M.TOUBEAU***,LL.LEFAIX*, G.FAYART*,A.LE PAPE** and F.DABURON* * CEA-IPSN-DPS-SPE-LRA,91191 Gif-sur -Yvette, France. ** Labomte~e de Biophysique Cellulaire,INSERM U316,Toars,France *** CEA-IPSN-DPS-SHR.Insdtut Curie, 75005 Paris, France, INTEREST OF 201TL CHLORIDE FOR THE SCINTIGRAPHIC EVALUATION OF INFLAMMATION IN TWO MODELS OF IRRADIATED FOCI IN PIGS. At doses higher than 25 Gy, acute localized irradiationsusely induce delayed and extensive cutaneous and muscular damages,The aim of our study was to evaluate and follow the kinetics of the inflammation associated to these lesions.Two experimental models with a focal irradiation on the limb were developed in pigs.

Scintigraphies were performed after intraveinousadministrationof 148 MBq. 201TI chloride. First, the deep muscular ulceration process was followed in 6 pigs irradiated at either 30 or 60 Gy. An increase in thallium uptake was observed in both the area irradiated and the surroundingtissues and it was found to be closely related to the clinical evolution of the lesions. Based on the intensity of the f'~tation, three stages were identified.The determination of the rado0t) between dae lesion and a reference healty area located in the same limb, exhibited a progressive increase in the fixation that reached a maximum 4 months after irradiation. However, this model is limited by an associationof cellular and vascular events that are difficult to dissociated. Skin ulceration acts as an additional disturbing phenomenon. So, immediately after occurence of erythema, the irradiated skin was surgically removed. In this second model, 60 Gy irradiations were performed and followed by successive thallium seintigraphiesfor 10 months. After skin removal, the irradiated site and eicatrisation were normal, The extension of necrosis and sclerosis appeared to be reduced. At 60 Gy the lesions exhibited a progressive fixation reaching R=2.5-2.8 after 6 months then decreasing :4 months later.The contribution of the neovascularization in the kinetics of the thallium fixation was demonstrated by experimentationsusing 133Xe. Cellular events also occurred in the deep muscular uptake but the mecanism of such a process remains to be precised. In conclusion, 201TI chloride could allow an evaluationof the inflammationoccuring in radlo-leslons. To further precise this property, complementary studies are currendy performedon macmphagesassociatedto these inflammatoryfoci.

R. PERDRI$O'I~!, J.J. LE JEUNE1, D. CHOTARD1 , D. POULIQUENI, P. BEAU2, A. LEPAPE2, P. IALLET1 1 - Labo.de Biophys.,Fac. de Mgd., rue Hante de Recutre, 49045 ANGERS,F. 2 - Labo. de Biophys.Cell., Fac. de Mrd., 2 Bd Tonnellr, 37000 TOURS, F.

for

of new tumor

p-emitting

selective

microeapsules

The therapeutic potential of '3~I-Lipiodol was evaluated in 17 patients with primary hepatic malignancy. Eight patients with intrahepatic cholangiocarcinoma (CCA) received a mean total activity of 668 (SD 325) MBq via the hepatic artery. There were no systemic side effects. Comparison of scintigraphy with synchronous CT scans revealed tumour-associated activity in only one case. The cumulative radiation dose from two treatments was 9.6 Gy to turnout, 6.4 Gy to liver and 1.5 Gy to lung. The patient shows turnout stasis and has survived 22 months from the start of treatment. The remaining patients have shown tumour progression, with a mean survival of 7.0 (SD 9.2) months. Nine patients with hepatocellular carcinoma (HCC) received a mean total activity of 1100 (SD 549) MBq. The treatments were well tolerated and selective localisation of the isotope was demonstrated in all 9 patients. The cumulative radiation dose was 33 (SD 34) Gy to tumour, 3.7 (SD 1.6) Gy to liver and 3.9 (SD 1.9) Gy to lung. Partial turnout response (reduction in tumour size > 50%) was seen in 6 patients, one of whom shows complet e turnout necrosis on biopsy. The mean survival to date is 8.5 (SD 6.4) months. Selective retention of '~ll-Lipiodol by CCA has not previously been reported. ~q-Lipiodol can deliver highly selective internal irradiation to foci of HCC with objective response in 2/3 of cases, and may be of value in a few patients with unresectable CCA.

A. MARY, P. HENROT, C. SCUTENAIRE, B. AERTS, R. DEREYMACKER I J. QUIVY. MEDGENIX GROUP, Fleurus, Belgium.

M. WAUTERS

Z-CMIV A STEROID CARRIER FOR TARGETED AUGER ELECTRONS RADIOI~HERAPY.

radiotherapy

This study concerns our initial findings on the preparation, properties and use of biodegradable microeapsules loaded with colloidal Rhenium 186. This radionuclide is characterized by a reasonably long physical half-life of 90h and a strong [3 emission (1 May). A single gamma emission of 137 Key made possible the study of capsule biodistribution, the acquisition of scintigraphic images and the evaluation of the dose delivered to the tumor. Biodegradable microcapsules, 10-15 g m in diameter a r e manufactured either by interracial-polymerization of isobutylcyanoacrylate encapsulating Re 186 or by solvent evaporation of a polylactic acid solution. Microcapsules are injected via the single pedicular artery of B-16 melanoma induced in mice (C57 B1 6/J strain) and metabolic follow-up is assessed by MRS on a AM 200 WB Braker spectrometer. VX2 hepatocarcinoma was also induced in rabbits and followed by MRI and CT-Scan before and after intra arterial injection of microcapsules. The results demonstrated that more than 90 % of the radio-activity injected reached the tumor. Spectra obtained showed a decrease in the ATP/pi and PCr/Pi ratios related to the dose delivered. Furthermore, in comparison with non-treated controls, irradiation arrested minor growth. Survival of both mice and rabbits models was significantly in creased. These preliminary results seem to show that high dose radiation can be delivered to tumor areas with microencapsulated 13-emitting radionuclides.

634

I N T R A H E P A T I C I R R A D I A T I O N OF C H O L A N G I O - AND H E P A T O C E L L U L A R C A R C I N O M A USING ~ % L I P I O D O L

PO-3L1-98

PO-3L1-97

Development

J R Novel_l, A Hilson', N Markham, A Green, K E F Hobbs Hepatobiliary and Liver Transplantation Unit," Dept. of Nuclear Medicine, The Royal Free Hospital, London NW3 2QG, UK

The new steroid, Z-CMIV (Z-II~ - chloromethyl-17~ iodovinyl estradiol), has been described as a high affinity ligand with high selectivity for the estrogen receptor (ERI. Radioimaging experiments with Z-CMIV labelled with iodine 123 allowed us to visualize clearly the MCF-7 human tumour containing ER receptors, grafted onto nude mice from 6h to 48h pest injection. Because of the nuclear localisation of the estrogen receptor the steroid Z-CMIV is a good candidate to study the feasibility of vector mediated Auger electrons radiotherapy. In a first step, this is assessed by experiments of inhibition of cancer cell culture proliferation (DNA content assay) with iodine 125 and 125 radiolabelled Z-CMIV. A strong arlti-proliferative effect is observed from doses of 2 microcuries of Z-CMIV/ml incubation medium. At the sam~dose, sodium iodide IiZ3 or I125 have no or little effect on cell proliferation. In a second step, MCF-7 cells are incubated in the presence of Z-CMIV labelled with iodine 123j in the presence of 'cold Z-CMIV or in the absence of any agent (control group) and injected subcutaneously in different groups ~ nude mice. Tumour growth was greatly delayed in the group of Z-CMIV I123 treated cells compared with the control group. Cold Z-CMIV treated group shows no difference of evolution with the control. Our new data suggests the potency of this type of ligand labelled with an Auger electron emitter to achieve targeted radiotherapy of estrogen receptor positive tumours. This work is suppertedby an European E U R E K A g r a n t (EU/181/18).

Tuesday, 3 September 1991

PO-3L1-99

PO-3L1-100

P.Riva*M.Mariani:.E.Seccamani:G.Moscatelli*P.G. Natali^L.Zardi+N.Riva * G.Franceschi*.A.Spinelli*G.Vecchi etti* *Ist. Onc.Romagnolo § Nucl.Med.Dept. Cesena:SORIN Saluggia^Nat. Cancer Instit. Rome +Nat. Cancer Inst. Genova ITALY DIRECT INTRATUMOR INJECTION OF MOAB-II31 IN BRAIN GLIOMAS 9 patients with bulky brain gliomas following the failure of repeated operations and/or radiotherapy were treated with a specific Monoclonal Antibody (MoAb BC2 SORIN-BIOMEDICA) recognizing an epitope on human tenascin and labelled with I131. Tenascin is a high weight glycoprotein expressed by the stroma of several different tumours and in particular it is found in malignant SNC gliomas , The radidpharmaceutical has been injected directly in the tumour mass by using the stereotaxis technique. The MoAb dose ranged from 0.5 to 3mg (moan 1.80 mg); the 1-131 dose ranged from 3 to 22 mCi (mean 13.01 mCi). Most patients underwent multiple injections. The hematologic,hepatic and renal toxicity resulted absent;the cerebral untoward effects were mild (headache). Only 2 pat. developed HAMA (titer 1:2) 3 months after the first RIT .The MoAb uptake in the tumour per gram resulted quite high (mean value 1.68% at 24h);the MoAb effective half life in the neoplastic mass (mean value 71 h) and the radiation dose delivered to the target tissue (mean ~00 cGy per mCi of I131) were much higher with respect the values achievable by means of the intravenous injection (respectively 0.002%,35 h and 35 cGy).The tumour/background ratio 24 hour after the injection was,on mean. 17.6. The cumulative radiation dose to the neoplastic mass ranged from 5000 to 20000 cGy (mean 13.900). 2 patients are not still evaluable, In the remaining 7,we recorded two progressive disease.two stabilisation of the disease (lasting 5 and 3 months) two partial tumour remission (one lasted i] months and one still lasts for 5 months) and one complete tumour remission still persisting for 9 months.

TOMASELLA G,CASARA D,RUBELLO D,PIOTTO A,PELIZZO MR, BOCCATO P,PICCOLO M,BUSNARDO B. Departments o~ Radiotherapy an~ Nuclear Nedicine, Radiology, Surgery, Semeiotica Medica~ Hospital of Padua.

PO-3L1-101 Tyson I, Martin M, Heal A, Ramirez G, Tenorio L, 'Ketc~ E, Greenberg H, Silbiger M. USF/JAMES A. HALEY VA HOSPITAL, TAMPA, FLORIDA SIDE EFFECTS APPARENTLY WITHOUT MEASURABLE TOXICITY DURING THERAPEUTIC P~GIMEN USING 131-I-MONOCLONAL ANTIBODIES (131-I-MOAB) IN PATIENTS WITH OVARIAN OR COLONIC ADENOCARCINOMA. Administration of diagnostic and therapeutic doses of 131-I labelled F~4FGI, a murine monoclonal antibody (MoAb) (Unipath England) was monitored using renal parameters serum BUN (BUN), creatinine (Cr), uric acid (U) and urine volur~ and creatinine (~__)° This report ~ill emphasize the importance of mino~Lchanges in parameters which may have mixed function such as Cr and U . Results: During periods of 2-10 day post in~raperi~oneal (IP) administration 131-I~HFGI in a dose range 0.6-30 mg (i.0-I00 mCi 131-I) HMFGI and over the therapy periods, i0 days to 8 months, no change in Cr and U could be ascribed to a massive change in nitrogen ~alance. C r dropped from 8030ml/min during periods of 2-i~ days following IP MoAb, the duration may be related to the mass of 131I-HMFGI administered IP. Other parameters suggest changes in osmolar filtered load and fractional excretion of sodium. Short term renal function loss may occur in antibody responses, eg. transient glomerulonephritis of streptococcal initiation in which apparent complete resolution may occur. Loss of renal function, for periods of up to 40 minutes, secondary to angiographic studies, without apparent untoward effect may occur. Particulate glomerular obstruction as either a result of complement absorption or particulate (macro- molecular) deposition on glomerular endothelial cellular foot processes with resultant loss of Ccr could be speculated upon. Studies with glomerular and tubular function eloments are presently being evaluated in currently surviving patients.

NKCKULTHASONOGRAPHY (US) VS TOTAL BODY SCAN (TBS) IN THE FOLLOW-UP OF DIFFERENTIATED THYROID CANCER (DTC).

In recent years an increasing interest on neck US in patients (pts) with DTC has been reported. The present stu dy was undertaken to investigate the effective role of US in the follow-up of these pts comparing US results to TBS. We considered 65 pts treated by total thyroidectomy for DTC and with pathological high serum Thyroglobu]in levels (Tg). They were studied by means of US, TBS, conventiona] radiology, CT scan and FNA cytology. 19 pts presented lymph node metastases (LNM), Ii mediastinic M, 17 lung M, 14 bone M; in other 4 pts, normal thyroid rem nants were found. US-LN image was considered pathologic when the ratio of trasversa] to longitudinal diameters was > 0.65 and when LN showed a hypo- or iso-echoic pattern. TBS resulted positive in 49 pts: 9/14 (64%) cases with bone M, 9/II (82%) with mediastinic M, 14/17 (82%) with lung M, 13/19 (68%) with LNM (I of them was US-nega tire) and in the 4 cases with thyroid remnants. US revea led pathologic them were

3 of

images

in

14/19

TBS-negative.

(73%) In

cases

conc]usion,

with neck

LNM a n d US r e -

presents a usefu], easy and sensitive technique in the follow-up of pts with DTC to search LNM. It may be recom mended to routinely associate neck US to Tg assay in the follow-up of pts with DTC. Moreover, in oases with path 2 logical high serum Tg values but with negative neck US investigation, TBS has to be performed to search distant M.

PO-3Ll-102 D Szeinfeld, N de V i l l i e r s , § Wynchank Research I n s t i t u t e f o r Medical Biophysics Medical Research Council, Parowvallei, R S A EXOGENOUS ATP AND ITS GLUCOREGULATORYRESPONSE AFTER FAST NEUTRON IRRADIATION IN NORMALRODENT TISSUE This work studies the role of exogenous Adenosine-5'-triphosphate (ATP) in modifying r a d i a t i o n damage. BALBc mice received l e t h a l whole body neutron i r r a d i a t i o n (6 or 7 Gy) from a therapy beam, p(66MeV)/Be. Survival (with an endpoint of 7 or 30 days) and activities of hexokinase, lactate dehydrogenase and acid phosphatase in testes were investigated. ATP was administered by i n t r a peritoneal i n j e c t i o n before i r r a d i a t i o n (Group I , n = 48). Other mice received only neutron i r r a d i a t i o n without ATP (Group 2, n = 39). (This work has been approved by the Ethical Committee of the S A Medical Research Council). The survival fractions following neutron i r r a d i a t i o n f o r Group 1 were more than twofold those of Group 2. The a c t i v i t y of acid phosphatase showed a marked increase at a l l the times a f t e r i r r a d i a t i o n but with less augmentation in Group i than in Group 2. The a c t i v i t i e s of l a c t a t e dehydrogenase and hexokinase show a pronounced decrease a f t e r r a d i a t i o n alone. But a f t e r administration of ATP p r i o r to the neutron i r r a d i a t i o n a clear increase in a c t i v i t y is seen. Thus exogenous ATP administered before neutron irradiation clearly provides radioprotection by increasing s u r v i v a l , by augmenting a c t i v i t i e s of the metabolic indicators hexokinase and lactate dehydrogenase, which are involved in physiological glucoregulatory processes, and by decreasing a c t i v i t y of the l y t i c enzyme acid phosphatase.

635

Tuesday, 3 September 1991

PO-3R1-1

PO-3R1-2

A. Ammann, B. Bliiuenstein, P.A. Schubiger, K. Seybold% J.T. Locher* Paul Scherrer Institut, Labor fiir Radiopharmazie, CH-5232 Villigen PSI '~ Kantonsspital Aaran, Nuklearmedizin, CH-5001 Aarau ANTIBODY LABELLING WITH TC-99M AND 1-123: QUALITY

W. Brandau, B. Vollet, O. Schober, I.G.B~ttger Klinik und Poliklinik fflr Nuklearmedizin, Westffilische Wilhelms-Universitat, D-4400 Mfinster, Deutschland

CONTROL ASPECTS For a period of several years the ab47, an antigranulocyte ab, has been labelled routinely with 1-123 (Iodogen method) for the diagnosis of infections. Now we have labelled the same antibody with Tc-99m using a new approach of a tailormade telraamine ligand which is first covalently bound to the ab. In a second step tin chloride and a suitable buffer are added. In the last step pertechnetate is added which after reduction by the tin forms a stable Tc(V) amine complex with the ligand. If the parameters, such as temperature, pH, salt concentration and type of buffer are carefully chosen, good results in vitro and in vivo (patients) are obtained. The labelled products are analyzed by UVspectrophotometry, thin layer and gel chromatography, and the specific binding to freshly isolated granulocytes from human blood was determined. A slightly impaired quality is visible in a lower specific binding to granulocytes (the nonspecific binding is often enhanced) and increased blood pool activity. Preparations of damaged ab47 show the presence of aggregates in the UV spectrum and virtually only nonspecific binding to granulocytes. First investigation show that good results in vivo are obtained with both nuclides.

QUALITY CONTROL OF 99mTc-HMPAO IN THE DIAGNOSIS OF BRAIN DEATH The confirmation of brain death with 99mTc-HMPAO scintigraphy has been shown to be useful, noninvasive and without additional risks for the patient. Nevertheless, caution is required because problems being associated with the instability of lipophilic 99~Tc-HMPAO may occur. Thus, during the last 4 years we observed 6 false positive results in normal cerebral perfusion imaging using ~ T c - H M P A O . In all cases labeling failure could be identified as having been responsible for these pitfalls. In order to enable a safe diagnosis of brain death an individual radiochemical quality control of the radiopharmaceutical prior to the investigation has been introduced. Only preparations with a radiochemical purity > 90 % were administered. In vitro quality control can be done by fast chromatographic procedures (TLC, HPLC) and subsequent quantification of the data (TLCscanner, gamma camera) within I0 - 15 min after preparation. Additionally, in vivo quality control by scintiphotos of thyroid, lung and liver is recommended. In conclusion the diagnosis of cerebral death by planar brain scintigraphy with 99mTc-HMPAO can be further improved using these in vitro and in vivo procedures, especially with regard to the fast and easy handling of the methods mentioned above.

PO-3R1-3

PO-3R1-4

M.Papadopoulos, E.Chiotellis. A.Varvarigou, S.Stathaki, M.Hioha-Skrettas*. Radiopharmaceutical Lab, R.C.P.S. "Demokritos" * National Hellenic Research Foundation, Athens, Greece,

D. Crombez, G. Bormans, M. De Roo and A. Verbruggen. Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

LUNG UPTAKE OF NEUTRAL, LIPOPHILIC NOTHIOL COMPLEXES.

Tc(V)-AMI-

In a project of studying a strueture-biodistribution relationship of eSmTc-DADT complexes, we have synthesized a variety of M-alkylDADT derivatives. In the present work the pulmonary accumulation of two subclasses of DADT compounds is investigated. The classes are comprising pyrrolidinyl and piperidinyl derivatives substituted in position 4 of DADT.Methyl, ethyl or phenyl groups were attached to heterocyelie amine backbone. After purification by HPLC, the SSmTc-D/d)T complexes were administered in animals and biodistibution studied at 2-30 min p.i..Radioaactive species injected, corresponded to lipophilic Tc(V)-DADT compounds.All complexes studied exhibited a high degree of lung aeeumulation.A well defined structure-activity relationship was found to exist in both subclasses with a linear correlation between %ID in lungs and partition coefficient (oetanol/phosphate buffer at pH=7.4). Pyrrelidinyl ee=Tc-DADT complexes been more lipophiilic, exhibited higher lung uptake in comparison to pireridinyl analogues.The highest lung uptake was obtained with SO=To-3,4 dimethylpyrrolidinyl-ethyl-DADT (80%-13% Dose per gr lung, during the time course 2-30 min p.i).Therefore OSaTe-DADT complexes as previously indicated (Lever, J.N.H. 29, 789, 1988) may be useful for lung studies.However, the mechanism of lung uptake has to be determined.

636

COMPARISON OF DIFFERENT TLC METHODS FOR THE ROUTINE ANALYSIS OF 2-[lSF]-FDG 2-[18F]Fluoro-2-deoxy-D-glucose (FDG) is currently the most intensively used radiopharmaceutical in PET. It is now generally prepared by the [lSF]F- displacement of the 2-triflate ester of tetlaO-acetyl-g-mannose in the presence of kryptofix 222 followed by the acidic hydrolysis of the ester functions. Potential radiochemica] impurities in FDG are therefore [18F]fiuoride and 18F-labelled O-acetyl derivatives of FDG originating from incomplete hydrolysis of the ester functions. Small amounts of klyptofix 222 can also be present as chemical impurity. We have compared different TLC systems on silicagel (Kodak) eluted with mobile phases that are described in literature for the assessment of the radiochemical purity of FDG preparations: TLC I : CH3CN/H20 95:5; TLC II : 0.1% Et3N in MeOH; TLC III: MeOH/NH4OH 9:1 and TLC IV : EtOH/EtOAc 1:5. The Rf-values of FDG and its possible contaminants in these systems are summarized in the table. Rf TLC I TLC II TLC III TLC IV tetra-O-Ac-FDG 1 1 1 1 FDG 0.28 0.54 0.58 0 F0 0 0.52 0 Kryptofix 222 0.06 0.20 0.41 0 Developing time 10' 17' 30' 25' Kryptofix can be detected by iodine vapours. Its detection limit (100 ng) is comparable for all TLC systems, but only TLC I and II supply specific Rf values. In contrast to published results, FDG remains on the application point in TLC IV, possibly due to a different brand of TLC strip, TLC III does not separate F- from FDG. Analysis of HPLC-purified FDG shows that all systems are characterized by aspecific adsorption on the application point resulting in a systematic underestimation(+2%) of the radiochemical purity of FDG preps. TLC II suffers from overlap of the F- and FDG spots as a result of the tailing of FDG. TLC I provides the fastest but yet an accurate method for separation of F- from FDG.

Tuesday, 3 September 1991

PO.3R1-6

PO-3R1-5 M. T. Ercan Department of Nuclear Medicine,Hacettepe 06100 Slhhiye, Al~kara, T~rkiye

L.K~Sr6sl~ Gy.A. Jltnoki, J.Szab6, J.Holland +

University,

RAPID DETERMINATION OF }FI~ROLYZED-REDUCED 99mTc IN PA~tTICI~A~ RADIOPHARMACEIF£ICALS It is possible to determine the amount of pertec~etate (99mTc04-) but not the hi~rolyzed-reduced (H-R) 99mTc in particulate radiopharmaceuticals (RP). We tested acid citrate dextrose (ACD) solution to facilitate the migration of H-R-99~Tc. As particulate RP's kits of h i ~ n ser~.~ albumin macroaggregates (MAA), microspheres (MSA) and nanocolloid (NC) obtained from commercial suppIiers, latex particles with either amine or carboxylic groups and liposomes prepared in-house were used. Kits were labelled according to the directions and the others by the tin reduction method. 99mTc-Sncolloid was also prepared. ITLC-SG strips were cut into 1.2x10 cm strips. Each radiop~rmaceutical ~.~.a alkalyzed both in methyl ethyl ketone (t-~K) ar~ ACD solution. ~ e development time for each was 2-3 min. The strips were cut into two pieces I cm above the point of application and ce~ited. All 99mTc labelled particles remained at origin. 99~Tc04 - migrated to the solvent front in both solvents (>99 %). 9~mTc-Sncolloid remained at origin in ]IE~, but migrated in ACD (>99 %). % 99mTc04- was determined from MEK and the total radiochemical impurities (99mTc04- and H-R99fnTc) from ACD strips. In 99~Tc kits where Sn is incorporated into the particles the amo~mt of H-R99~Tc T,~.s
Natl."F.J.C." Research Inst. for Radiobiology and Radiohyglene, Budapest~ Hungary EVALUATION OF 99mTc ANTI CEA MONOCLONAL ANTIBODY: RADIOCHEMICAL PURITY~ STABILITY AND LOCALIZATION IN A COLORECTAL TUMOUR XENO(IRAFT MODEL. In this work the labelling efficiency, stability and tumour uptake of anti CEA MoAb labelled with 99roTe via activated thiol groups was studied. Radlechemical purity and stability was determined with TLC and radio HPLC. HPLC analysis or MoAb was performed with BIO-RAD HPLC system. Samples were eluted with 0 . 0 2 M Na2HPO4/O.O5 Na2SO4 buffer of pH 6.8 and flow rate of 1 ml/mln. Absorbance at 2 8 0 nm, gamma radiation with flow-through detector were measured. During polyacrylamlde gel electrophoresls (PAGE) samples were applied to 7.5 % non reduced gel and O.2 M phosphate buffer of pH 7.6 was used.

The blodlstributlon of 99mTc anti CEA MoAb (1-48 hrs) was determined In mlces bearing CEA positive human eolorectal tumour xenografts. The labelling yield was always higher than 95 %. 20mln 3hrs 6hrs 24hrs free99raTcO4% 1.9-+0.1 1.5-+0.2 3.9-+0.2 7-9 99mTc-stannous component % 0.7_+0.1 2 . 2 + 0 . 2 I hrs 6 hrs 12 hrs 24 hrs I.D. %In gr tumour 2.2 -+0.6 3.2 -+ 1.3 3.6 _+1.5 8 . 5 -+ 0.9

The HPLC study showed low dlmer lgG(<3%) and high monomer lgG (.95%) content. No fragmentation was detected by PAGE also. During the first two hrs post injection of the 99mTcanti CEA MoAb most of the activity remained in the blood pool (25-40%) and the parenehymatous organs. After 24 hrs high tumour, liver and bowel activity was observed. The tumour contrast was good allowing turnout detection as earlyas 3 hrs post Injection. The intact anti CEA MoAb labelled with 99mTc showed, high redlochemical purity, stability and high accumulation In the tumour tissue.

PO-3R1-7

PO-3R1-8

R.W. LIPP, A. Passath and G. Leb Division of Nuclear Medicine, Department of Internal Medicine, Karl-Franzens-University Graz, Austria

M Matarrese, R. J. Nickles, O. T. De Jesus, F. Colombo, E. Deutsch and F. Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy, University of Wisconsin, Madison Wl and BCRC, University of Cincinnati, Cincinnati, OH, USA.

THE FREQUENCYOF NON-IATROGENIC HUMAN ANTIMOUSE ANTIB0DIES IN THE STYRIAN POPULATION I t is essential to know the frequency of positive preexisting non-iatrogenic HAMAt i t e r s because t h e i r presence may influence the results of immunoscintigraphy, immunotherapy and immunoassays. The blood sere of 35 adults of both sexes, 10 infants (2 to 13 months) and 11 newborns and t h e i r mothers were examined with the Enzygnost HAHA micro assay, using the anti-granulocyte Hab BW 250/183 as binding antigen. A l l of the donors had never received a single intravenous i n j e c t i o n of murine antibody, however about 90 percent of the adults yielded positive t i t e r s of non-iatrogenic HAHA. Even the newborns exhibited IgG but no IgM values of maternal HAHA. The infants synthesized t h e i r own HAHA of both frec ~ions. Therefore, i t is important to determine the ni-HAHA t i t e r whenever murine antibodies are used for diagnosis or therapy. Equally the presence of non-iatrogenic HAHA in patients sere has to be taken into account when the results of enzyme immune assys using morine antibodies (e.g. serum-CEA) ere evaluated,

STUDIES ON THE CHEMICAL PROPERTIES OF Mn-52m.

AND

BIOLOGICAL

Mn-52m (21.1 min half life), is a positron emitting isotope which can be readily produced in large quantities with small cyclotrons by proton bombardment of a metallic chromium target [Cr-52(p,n)Mn-52m] [Nickles et al., J.Nucl. Med. 29: 932 (1988)]. The aquo ion, [Mn-52m-aq]2+, has been proposed as a PET myocardial imaging agent, and other Mn52m complexes might function as PET imaging agents. In order to establish if the chemical and biological properties of the substitution labile Mn(ll) center can be modified by addition of appropriate compounds, [Mn-52m-aq]2+ was brought into reaction with several ligands, and then the percentage of.activity which could be extracted from octanol was determined. The following three ligands generated complexes with the. highest octanol extraction efficiencies: d,l-hexamethylpropyleneamine oxime (d,I-HM-PAO, 69%), sodium diethyldithiocarbamate (DTC, 93%), and potassium hydrotris (1-pyrazolyl) borate (98%). Since only less than 5% of the parental aquo ion [Mn-52m-aq]2+ is extracted from octanol, these results indicate that all three ligands give rise to relatively lipophilic Mn-52m ligand complexes. These initial experiments show that a variety of ligand classes can be used to convert the aquo ion [Mn-52m-aq]2+ into Iipophilic Mn-52m complexes. However, useful Mn-52m agents will have to be based on multidentate ligands which undergo only slow displacement from the Mn(ll) center.

637

Tuesday, 3 September 1991

PO-3R1-9

PO-3R1-10

F. Melichar ~, Ju.I.Vereshchagln , K. Svoboda Nuclear Research Institute, ~e~, Czechoslovakia XXThe Kurchatov Institute of Nuclear Energy, Moscow, the USSR THE USE OF ENRICHED 98-Mo FOR THE PREPARATION OF 99m-Tc BY THE (n,~) REACTION AND ITS REGENERATION

J. MERTENS, H. MOEREELS*, I. ZOLLE** VUB-Cyclotron, B-1090 Brussel *Janssen Research Foundation,B-2340 Beerse, **Nucl. Med., 2 Medizinische Universit~tsklinik A-1090 Wien.

At present, there exist three types of 99m-Tc generators - the sorption, the extraction, and the sublimation ones. For bulk supplies to large health centers, the introduction of large extraction generators that process irradiated 99-Mo, obtained from enriched 98-Mo by the (n,~) reaction, seems to be very advantageous. Such a generator operates as a compact extraction unit, fully automated. The extraction generator makes it possible to produce up to 120 C i ~ 4.40 TBq 99m-Tc per week. The content of contaminants in an injection of 99m-Tc sodium pertechnetate is 99-Mo 2.10 -7 , 131-I 1.10 -6 , 103-Ru 1.10 -6 , the content of other contaminants being by 2 - 3 orders lower than that of sorption generators. The regeneration of enriched 98-Mo is a part of the production line. The regeneration of the 98-Mo target material, in the form of potassium molybdate, after finishing the extraction of 99m-Tc is performed discontinually in a special device for regeneration. This way of production permits one to increase substantially the possibility of manufacture of instant 99m-Tc for the surrounding medical terrain and, simultaneously, to increase considerably the utilization of the capacity of a local reactor.

PO-3R1-11 J. YU, I.Zolle, M. Berger*, and R. H~fer Nucl. Med. 2nd Medical Clinic, *Institut Biochemische Pharmakologie, A-I090 Wien

Several attempts were made to develop a radiolabelled Metyrapone analogue as an in vivo adrenocortical and derived tumors imaging agent• Replacement of the A-dng pyddyl group by a phenylring enhances the activity as compared to the original compounds. An additional increase of the lipophilicity by introducing halogen substituents may result in high aspecific binding. In order to overcome this inconvinience we used the principal of compensated lipophilicity and propose the tollowing analogues :

/

Y-i\

~

0

CH3

/2--c--?-7F

Y=H Y=F Y=F

X=Br:l or I : Z X = B r : 3 or 1:4 X = H :5.

As a mesure of lipophilicity the SAA's (solvent accessible area in .~2 proportional to log P) using a 1.5 A probe are calculated.Compared to the unsubstituted analogue (X = Y = H) the increase of SAA of the proposed analogues is respectively 7.4 for 1, 11.4 for 2, 13•5 for 3 and 16.5 for 4, while meta substitution shows an increase of at least 40.0 A t Compound 1_(the firsttried in the series) shows the highest binding affinity as compared to eadier developed analogues (1) The radioiodinated compounds ~ and 4 are easily obtained by Cul + assisted non-isotopic exchange on .1.and 3. A potential PET tracer 5 can be obtained by 'eF- for NO 2 exchange on the activated para position. (1) Zolle, I ;Yu, Jet aL J. Lab. Compd. Radiopharm. XXIX (3), (1991).

PO-3R1-12 M. BANYAI, G. LUPATELLI, I. VIRGOLINI, J. PIDLICH, f.

EVALUATION OF METYRAPONE-DERIVATIVES AS PRECURSORS FOR LABELLING WITH RADIONUCLIDES Derivatives of ring-A phenyl-metyrapone have demonstrated highest binding to adreno-cortieal mitochendria when compared with metyrapone, metyrapol and 4'-bromo-metyrapone (Zolle et al. 1991). ICs0-values calculated from binding studies with 3H-metyrapol and various metyrapone analogues emphasize the competitive binding capacity of the 2-substituted phenyl-metyrapone derivatives. Enzyme-binding of metyrapone is rapid and remains constant for a longer period. Addition of excess unlabelled metyrapol (500nM) showed saturability of binding sites. When rat adrenal tissue slices were incubated with the binding solution for 1 hr, autoradiography revealed a dense blackening of the film in the cortical region, indicating exclusively cortical binding. Biodistribution studies in rats using 131I-2iodo-phenyl-metyrapone labelled by the Cu +lassisted method (Mertens et al. 1987) confirmed high adrenal uptake of the tracer. References Merte~s, J., Vanryckeghem, W., Gysemans, M., Eersels, J., Finda-Panek, E., and Carlsen, L.. Eur. J. Nucl. Med. 13, 380-381, (1987). Zolle, I., Yu, J., Robien, W., et al.. J. Labelled Compd. & Radiopharm. XXIX(3[, (1991).

638

DESIGN OF RADIOHALOGENATED METYRAPONE ANALOGUES AS POTENTIAL IN VIVO TRACERS.

P. ANGELBERGER,H. SINZINGER LDL-RECEPTOR ACTIVITYOF LYMPHOCYTESFRESHLY ISOLATED FROMPATIENTS WITH FAMILIARHYPERCHOLESTEROE~MIA ( FH ) The number of LDL-receptors as well as their a f f i n i t y to apoIipoprotein B-tO0, the only apolipoprotein of the major cholesterol-carriers in bloo~, namely low-density lipoproteins, were de~ermined in a radioligand-binding study. Fiftyfour ml of peripheral venuous blood were anticoagulated with sodium-citrate (3.8%) out of which the lympocytes were isolated by a single-step density-gradient centrifugation. The cells were then incubated with increasing concentrations of 123-I-LDL (1-60 ~g protein/m]) either in the presence or absence of excess unlabeled LDL at 4"C for 45 minutes. Radioligand-binding studies were subject to Scatchard analysis in order to determine the number of LDL-receptors and their a f f i n i t y to their ligand. Scatchard analysis revealed saturable, high a f f i n i t y (Kd 4 ~ 1.5 pg protein/ml) receptor sites for LDL particles in healthy c,'mtrols as well as inFH patients. Specific binding was in the range of 90% in both groups whereas the number of high-affinity binding sites was significantly (p< 0.01) reduced in FH-patients. These in vitro findings correlated with the hepatic uptake of 123-I-LDL respectively 1111n-LDL in the same patients. I t is concluded that determination of LDL receptor activity of l~nnphocytes in-vitro and hepatlv LDL receptor activity in vivo could provide a valuable tool for :he diagnosis of FH. This study was supported by a grant of the ~sterreichische Nationalbank, Jubil~umsfond, Project Nr. 3778.

Tuesday, 3 September 1991

PO-3R1-13

PO-3R1-14

P.H. Cox, M. Pillay and O.H.W. Seh~nfeld Or, Daniel den Hoed Cancer Centre, P.OoBox 5201, 3008 AE Rotterdam, NL.

S.Danilov, H.Hiemisch, E.Atochina, V.Gavrilyuk, V.Muzykantov USSR Cardiology

THE MECHANISM OF TECHNETIUM TUMOURS

MIG COMPLEX UPTAKE IN

Research

Center,

M.Slinkin,

Moscow,

USSR.

I M P R O V E D L U N G A C C U M U L A T I O N OF M O N O C L O N A L A N T I B O D Y TO A C E A F T E R A D S O R P T I O N ON C E L L U L O S E

Technetium 8gm pelyolenal IgG complex has recently been introduced as e radiopharmaceutieal for the detection of focal sites of active inflammation by means of scintigraphy. Accumulation has also been reported in tumour tissue. The object of this investigetien was to examine the degree of up~ake of Technetium igG in tumours and to determine to what degree this was due to non specific binding. MATERIALS ANO METHODS. Technetium lgG complex was prepared ~coording to manufacturers instructions using a commercial labelling Kit (MallinoKrodt HIG). 22MBq of activity was injected intravenously into r a t s bearing eoloreotal tumeurs. The biDdistribution ~as monitored during one hour post injection by oontinuous gamma camera scintigraphy. RESULTS AND CONCLUSIONS, There was a rapid accumulation o~ activity in the tumour tissue which reached e maximum at ~ 4 min post injection. The tumour to muscle uptaKaratios were 5:1 which was ~avourable to scintigraphy. A continuous washout of activity from the tumours was observed after the maximum concentration had been reached. This was parallel to similar deoreases in muscle and blood pool activity observed at the same time. The data suggests that whilst the initial concentration of IgG complex in the tumour was adequate for scint±graphy there is no significant binding o£ complex in the tumour tissue. The mechanism of accumulation is prssumably related to local aadsme fluid associated with inflammation at the tumour site. This would imply that tumours with little or no inflammation would be difficult to visualise.

P r e v i o u s l y it w a s s h o w n t h a t m o u s e m o n o c l o n a l a n t i b o d y (MoAb) to a n g i o t e n s i n - c o n v e r t i n g enzyme (ACE), n a m e d 9B9, r a d i o l a b e l l e d by I-I25, I n - I I I a n d T c - 9 9 m a c c u m u l a t e s s p e c i f i c a l l y in lungs of rat, h a m s t e r , cat, m o n k e y a n d human. Furthermore, we have demonstrated that MoAb 9B9 lung a c c u m u l a t i o n is a s e n s i t i v e m a r k e r of lung v e s s e l injury. T h e a i m of this s t u d y was i m p r o v e m e n t of l a b e l i n g / p U r i f i c a t i o n procedures for M o A b 9B9 and e v a l u a t i o n of t h e i r s t a b i l i t y . S t a b i l i t y a n d i m m u n o r e a c t i v i t y of the m o d i f i e d and p u r i f i e d r a d i o l a b e l e d M o A b 9B9 w e r e a s s e s sed by b o t h in v i t r o and in v i v o a n t i g e n ( A C E ) b i n d i n g assay. R a d i o l a b e l l e d M o A b 9B9 w e r e p u r i f i e d by i) ads o r p t i o n c h r o m a t o g r a p h y on c e l l u l o s e , ii) H P L C (gel f i l t r a t i o n ) , iii) a f f i n i t y c h r o m a t o g r a p h y on A C E - S e p h a r o s e . T h e b e s t r e s u l t w a s o b t a i n e d w i t h c e l l u l o s e : e f f i c i e n c y of M o A b 9B9 lung acc u m u l a t i o n (% of i n j e c t e d d o s e / g of lung) incr e a s e d to 2 9 . 2 + 2 . I f r o m I 7 . 0 + 2 . 4 for non-treated MoAb; s p e c i f i c i t y of this a c c u m u l a t i o n (expressed as c p m / g of lung to t h a t of blood) i n c r e a sed to 2 3 . 3 + 2 . 3 vs. II.I+I.6. We c o n c l u d e t h a t the p h e n o m e n o n of s p e c i f i c lung a c c u m u l a t i o n of M o A b 9B9 m a y s e r v e as an i d e a l (convinient, c h e a p and t e c h n o l o g i c a l ) assay s y s t e m for e v a l u a t i o n of m o n o c { o n a l antib o d i e s m o d i f i c a t i o n s and l a b e l i n g .

PO-3R1-15

PO-3R1-16

S.J. Mather, M. Granowska. T. Jobling and K.E. Britton. St. Bartholomew's Hospital, London UK.

I. Novak-Hofer 1, H.P. Amstutz 2, A. Haldemann~, H. R6sler3, K. Blaser 4, J.J. Morgenthaler 2, P. Bl~inenstein I, P.A. Schubigerl IPaul Scherrer Institut, Villigen, 2Zentrallaboratorium Blutspendedienst SRK, Bern, 3Abt. Nuklearmedizin, Inselspital, Bern, 4SIAF, Davos, Switzerland TUMOR TARGETING PROPERTIES OF RADIOIODINATED

INDIUM-Ill MACROCYCLE LABELLED ANTIBODIESRADIOLABELLING AND CLINICAL APPLICATION. The use of Indit~n labelled antibody-DTPA conjugates for Jarma~oscintigraphy results in an immediate high uptake by the liver and slowly increasing levels in the bowel and bone marrow. A possible cause of this nontarget uptake is release of indium frown the conjugate owing to inadequate in-vivo stability. The u s e of a chelator with a very high affinity for indium such as a macrocyclic chelator may reduce this problem. '9N3' is a macrocyclic chelator with a log formation constant for indium greater than 30. A maleimide derivative of 9N3 was conjugated to thiol groups produced by the reaction of 2-iminothiolane with a monoclonal antibody S~43. The preparation was purified by gel filtration to remove unbound chelator. The conjugate was labelled w±th In-lll and, after purification, 90-100MBq of the labelled conjugate was injected into 7 patients with a high diagnostic probability of ovarian c a n c e r . Serial gamma c~nera images were acquired and blood and urine sar~oles taken. The images did not differ significantly from those obtained in a similar group of patients imaged using Indium labelled ~ 3 - D T P A conjugates. Pbermacokinetic profiles were also comparable. In this small group of patients, the chelating agent was not a major detemninant of non-turnout uptake of Indium-lll indicating that the mechanism of uptake is not poor in-vivo stability.

CHIMERIC

ANTIBODY

CHCE7

IN

NEUROBLASTOMA-

BEARING ATHYMIC MICE A chimeric (mouse/human) monoclonal antibody (chCE7) of human

gamma 1, kappa isotype directed against a neuroblastoma associated cell surface glycoprotein is described. In vin'o chCE7 binds with high affinity (Ko - 1 x 10-10M) to SKN-AS human neuroblastoma cells. In vivo biodistributions of radioiodinated chCE7 in nude mice bearing SKaN-AS tumors were measured after 1, 2, 4, 5, 7 days. Maximal tumor uptake was reached after 24 h (31.9 + 4.0 % I.D./g., n = 4) and declined over a period of 7 days to 15.5 + 3.0 % I.D./g. Optimal tumor/blood ratios (3.4 : 1) were reached after 4 - 5 days. At all the time points'uptake in other organs, including the reticuloendotelial system was low with tumor/organ ratios of 10 or more. Stability of chCE7 during and after radiolabeling was good with no loss of immunoreactivity in preparations labeled with '231 up to 100 mCi/mg and 80 % immunoreactivity left after labeling with 13 mCi/mg of ~31I. Neuroblastoma xenografts were imaged by radioimmunoscintigraphy with 123I- and 131I-labeled chCE7. We conclude that the high affinity and selective tumor uptake in the xenograft system make chimeric antibody chCE7 a promising agent for neuroblastoma imaging and therapy.

639

Tuesday,

3 September

1991

PO-3R1-17 Briqitte Pesau, Irene Virgolini, Shuren Li, Christian Hunt, Peter Angelberger, ,.Johann Pidlioh, Helmut Sinzinger ,Dept. of Nuclear Medicine, I1. Dept. of Medicine, University of Vienna, and Chemical I n s t i t u t e R e s e a r c h C e n t e r Seibersdorf, Austria

PO-3R1-18 J.C.PITTET*, M.PEPIN*', H.BINZ**', G.NORMIER"*, A.LE PAPE*. *Laboratoire de Biophysique Cellulaire et RMN, INSERMU316,Tours. **Laboratoire de Pathologle Infectieuseet Immunotogie, INRATours. ***Centre d'lmmunologie et de Blotechnologie Pierre Fabre, St Julien en Genevois,France.

Thyroid dysfunction is known to have an important influence on lipid metabolism, but nothing is known about its influence on the lipoprotein (LDL)-receptors. In 10 patients platelet LDL-receptors were evaluated after total thyroidectomy for thyroid cancer as well as after a 2-3 months treatment period with levothyroxdin-natrium (0.150.25 mg daily). In the hypothyroid state (TT4: 2.16±0.66; FT4: 0.15±0.071 ; -I-13: 37.2-,-9.34; TSH: 48.46±2.81 ) the patients exhibited significant higher levels for total cholesterol ( 3 5 4 ± 4 1 . 1 m g / d l ) , L D L - c h o l e s t e r o l ( 2 5 5 . 9 ± 4 3 . 7 ) and apolipoprotein B (176.5±20.44) as normolipemic individuals. The capacity of platelets to bind 1111n-LDL was remarkably impaired (Smax: 3 5 1 ± 2 5 5 vs 1 5 6 2 ± 3 4 3 ng protein/109 platelets) whereas the binding affinity (Kd: 5.1±12.1 vs 4.2±2.1pg protein/ml) was unchanged. The competition of unlabelled LDL for I~qn-LDL binding (IC~0:23.4±12.1 vs 8.2±4.3pg protein/ml) was decreased in the hypothyroid state. Following substituation therapy normalization occured (TT4:13.61 ±2.56; FT4:1.81 ±0.65; TT3:111.77±27.17; TSH: 0.28±0.44; total cholesterol: 226.6±35.3; LDL-cholesteroh 143.5±34.37; apolipoprotein B: 108.5±24.6). This was a c c o m p a n i e d w i t h i n c r e a s e in L D L - r e c e p t o r s (Bma:x 9 6 2 . 1 ± 3 4 9 ng p r o t e i n / 1 0 9 platelets; K~: 4 . 7 ± 2 . 9 p g protein/mi; IC59:10.1±3.1 IJg protein/ml). These findings support the view that platelet LDL-receptors could be downand up-regulated, and that thyroid function has an important effect on this regulation.

LYMPHOSCINTIGRAPHY VIA THE TARGETING OF MACROPHAGES WITH J001 GLYCOLIPOPEFrlDE : STUDY IN THE EXPERIMENTALLY INDUCED INFECTIOUS GRANULOMAS IN SHEEP. In its present form, lymphoscintigraphy involves labeled microparticules or colloTds that distribute in the lymph or are carded by mononuclear phagocytes, Limitation often occur from the reduced permeability of infected or metastatic lymph nodes. So, visuatization of several pathological lymph nodes in the same chain is usually difficult. A strategy could be the targeting of macrophagss using a highly diffusible lymphotropic agent such as J001. In a previous study it was demonstrated that this 34 Kda glycolipopeptide isolated from Klebsiella, when administrated as an aerosol ,allowed to image small metastatic lymph nodes in mediastinum and axiUary, pepliteal and inguinal areas. In this study, J001 was labeled with 99mTc using SnF2 reduction and its efficacy as a lymphoscintigrephic agent was assessed in a model of infectious granulomas developed in superficial lymph nodes in lambs following subcutaneous inoculation in the hindlsgs with Corynebacterium pseudotuberculosis. Macrophage recruitment and accumulation in chronic granulomas induced by this bacteria were demonstrated by immunochemistry using a monoclonal antibody (Mab) raised against ovine maorophages. This massive recruitment of macrophages in the granulomas will be confirmed by immunoscintigraphy using this Mab labeled with ggmTc. Lymphosclntigraphies were performed in lambs, 1 to 3 months following experimental infection. 0.ling J001 labeled with 18.5 MBq 99roTs was intradermally injected. During the first 30 rain, lymphatic vessels were imaged all along the two hindlegs. Two hours after injection, images exhibited highly fixing pepliteal and inguinal nodes with a scintigraphic ratio ranging from 2 to 3. The second infected lymph node was not imaged by a usual tymphoscintigraphy using Antimony Sulfide, confirming the interest of a highly diffusible agent such as J001. Use of J001 has also allowed to image the lymphangitis which developed in early stages of bacterial dissemination. So, targeting of macrophagas with J001 glycolipopeptide which has been already described as a new strategy for imaging turnouts and inflammatory lesions should be also of use for lymphoscintigraphy . Studies are currently in progress to evaluate its efficacy to image metastatic lymph nodes in humans.

PO-3R1-19

PO-3R1-20

F. S c o n i n a r o , M. Di L o r e t o * , L. Di M a c i o , M. Banci,- A.Mele*, R.De Santls*, O.Schillaci, A.M. Anastasi*, A.Centi Colella S e c t . of N u c l e a r M e d i c i n e , D p t . o f E x p e r i m e n t a l Medicine, University "La Sapienza", Rome, and *Menarinl Ricerche ~ud,Pomezia, Italy

A. steinstr~aer, R. Kurrle, A. Schwarz, K.H. Sch~fer Hoechst AG /Behringwerke AG, Germany

I N F L U E N C E OF T H Y R O I D RECEPTOR REGULATION

FUNCTION

ON L D L -

ANTI CROSS-LINKED FIBRIN MoAb. A POSSIBLE SPECIFIC AGENT FOR RADIOIMMUNODETECTION OF THROMBI. F a c t o r V I I I c a t a l y z e s t h e f o r m a t i o n of c o v a l e n t bonds between the D fragments of c o n t i g u o u s fibrin monomers. Thus the DD fragment is a specific marker of cross linked fibrin. F 6 0 / 4 3 / 8 is t h e m o s t r e a c t i v e o u t of s e v e r a l a n t i DD M o A b o b t a i n e d in o u r l a b o r a t o r i e s . It does not show cross reactivity with fibrinogen. P l a s m a c o n t a i n i n g h u m a n c l o t s (0.5 q. o f c l o t p e r i0 cc of p l a s m a ) w a s m i x e d t o 125 I F A b o f [25 I n o n F60/43/8 and specific murine IgG. C l o t s w e r e w a s h e d w i t h P B S t w e e n 20 a f t e r 18, 24, 36 a n d 96 h r s a n d t h e r a d i o a c t i v i t y was measured. The results are shown as % of the total activity administered: F60/43/8 18 h: 41%; 24 h: 40%; 36 h: 34%; 96 h: 32% Non specific IgG 18 h: 8%; 24 h: 7%; 36 h : i . 7 % ; 96 h: 1% i0 r a b b i t s w e r e s t u d i e d in o r d e r t o a s s e s s t h e in v i v o b e h a v i o u r of F60/43/8. A clot was o b t a i n e d in a v e i n o f o n e e a r a n d t h e 131IFAb w a s i.v. i n j e c t e d in t h e o t h e r ear. T a r g e t / B K g r a t i o w a s h i g h e r t h a n 5 in a l l r a b b i t s ; t h e clot/liver r a t i o w a s 4+2 b o t h at 5 a n d 24 h. The anti-DD-fragment Mo-Ab t e s t e d in our. s t u d y shows high specific linkage with cross-linked f i b r i n . L a c k of c r o s s r e a c t i v i t y w i t h f i b r i n o g e n a n d h i g h a f f i n i t y t o c l o t s in v i v o s u g g e s t that radiolabelled F60/43/8 may be useful for radioimmunodetection of thrombi.

640

KINETIC STUDIES OF ANTI T-CELL-ANTIBODIES IN A HOMOLOGOUS MODEL Monoclonal antibodies against T-lymphocytes of men have been applied several times to prevent rejection of transplants. Yet there is little known about the kinetics of these antibodies. A systemic study on animal models is impossible in most cases due to a missing cross-reactivity. We used therefore a MAb directed against rat lymphocytes in our animal model. An anti CEA-antibody of the same isotyp was used in controls. Both antibodies were labelled with Tc-99m. Series of sequential scintigraphies during the first 2 h p.i. did neither show pooling nor redistribution phases, but on the whole a fast accumulation of the activity in the spleen. Organ distribution studies could therefore be restricted to 1 and 24 h p.i. The protein applied varied between 0.25 and i000 ~g (equivalent to 0.i 350 mg for men). The largest accumulation revealed in the spleen decreasing with time and increasing amount of protein. The activity in lymphocytes rises however with time, but is also the most in case of the least protein application. Above i00 ~g protein per rat the activity in blood is not essentially different from controls. A significant cell binding is not recognizable. Below I0 ~g cell binding appears high in the periphery (50-60 %) by a greatlydecreased activity concentration in blood. The antibody can be applied excessively for therapeutic purposes, but for scintigraphic studies only small amounts of protein are useful (~ I mg for men). The kinetics of labelled cells can only be recorded under such conditions, but then lymphatic organs are represented in high-contrast.

Tuesday, 3 September 1991

PO-3R1-21

PO-3R1-22

l.Szilv~si, l.Balogh, M . O m a r , J . T e n c z e r ° Dept. of N u c l e a r Medicine, P o s t g r a d u a t e M e d i cal School and 3rd Dept. o f M e d i c i n e , S e m m e l weis University of Medicine~ Budapest,Hungary

J.R. THORNBACK, B. LECLEF, P. CERFONTAINE, F. DONCEL, R. PIROTTE MEDGENIX S.A., Fleurus, Belgium and I.R.E., Fleurus, Belgium

1-123-MIBG SCINTIGRAPHY MYOCARDIAL INFARCTION

IN P A T I E N T S W I T H A C U T E

1-128-MIBG scintigraphy is a reliable diagnostic technique to study adrenergie i n n e r v a t i o n o f t h e heart. D i s t u r b e d s y m p a t h e t i c nervous function might have a role in g e n e r a t i n g v e n t r i c u l a r a r r h y t h m i a s in p a t i e n t s with acute myocardial infarction. Resting myocardial scintigraphy with To-99m-MIBI and 1-123-MIBG scintigraphy were performed in 12 patients with acute transmural myocardial infarction. Extent of perfusion and adrenoceptor d e f e c t s was estimated using SPECT. Scintigraphic data were correlated to clinical findings and continous ECGmonitoring. Localization of MIBG defects corresponded to the site of resting perfusion defects. The size of MIBG defect was significantly (p < o.oi) larger than that of MIBI. In 2 p a t i e n t s with.clinical e v i d e n c e of p e r i c a r d i a l i n v o l v e m e n t diffusely d e c r e a s e d I - I 2 3 - M I B G u p t a k e was found.Patlents w i t h large d i s c r e p a n c y between p e r f u s i o n and adrenoceptor distribution had more frequent venticular ectopic arrhytmias detected by H o l t e r ECG m o n i t o r i n g . In c o n c l u s i o n : c a r d i a c adrenerg innervation seems to be more s e n s i t i v e to i s c h a e m i c d a m a g e t h a n myocardial tissue. 1 - 1 2 3 - M I B G s c i n t i g r a p h y m a y c o n t r i b u t e to b e t t e r understanding of the g e n e s i s .of v e n t r i c u l a r a r r h y t h m i a s in p a t i e n t s w i t h a c u t e myocardial infarction.

NEW RADIOtABELLED MOLECULESWill{ HIgH SPECIFICITY FOR THE R£RIRdERAL BEN/I]DIt~EPINE RECEPII~ Unlike the central benzodiazepine receptor which are found primarily on neuronic tissue, the peripheral type is found p r i n c i p a l l y in the heart, adrenal glands and in certain tumours notably gliorna and coloa carcinoma. Thus, moleculeswhich bind to the l a t t e r could find extensive use in both oncology and cardiology. In this work we present the results of our studies with a new series of ligands which havea high a f f i n i t y for the peripheral benzodiazepine receptor but l i t t l e cross-reaction with the central receptor. Themolecules are a series of assymetric urea derivatives ofthe general fo ula whereX is an iodine atom : cold or or 1231 in

the o, m, or p position

The molecule where X = meta-ipeo has an IC50 value

of .2 x 10-9 M for the receptor and i n h i b i t s uptake of the reference ~H - PK 11195 and has been further developed. In rats the molecule shows good heart uptake 4.3 %/g tissue within 15 minutes although were out also discuss f a i r l y rapidly. Further studies are contisuing with this interesting series O{ new molecules and iS appears that the peripheral benzodiazepioe receptor sbows promise for use in c l i n i c a l practice.

PO-3R1-23

PO-3R1-24

N. P. L G. Verhoeff, ~ Bobeldijk, G.J. Boer, ~i G. P. F~ensr_ra, . K. Krur~ieck-Ez~te, and E.A van l~oyer~ ueparumen~ of Nuc±ear Medicine, Acaaemic Medic~l Centre, and Netherlands Ir~titute for Brain Research, A,sterdam, and Cygne B.V., TU Eindhoven, '±ne Netherlands.

S.E. S.A.

IN VITRO BINDING OF M U S C ~ N I C CHOLINERGIC R E C E ~ R S WITH 1-123 IODODEXETIMIDE IN RAT BRAIN 1-123 4-1ododexetimlde (I-123 IDEX) (opec. act 6000-6800 Ci~mmol ) has recently been synthesized by so{r@, oz us. 'zne present stu~ly is a zirst attempt to y~idate, this -igand for muscarinic receptor mlnalng ,z~ an in vitro study in rat brair~ In vi~_ro saturation bindincT experiments w-lth 1123 IDEX and H-3 ~ (opec. ac~ 4~ Ci/mn~l) were performed for me~u)rane ~_rb:i~tior~ of the hippocaE~pus (HI; n~tinly M1 receptors), cerebellum (ca) i~'i]ly M 2 receptors), and striatum (ST; ..rag-JulyMJ or M4 rece-pi~ors). Receptor specificity of v.ne p relm3+~ions %r~s investi~ted in displacement experlmenr_s of H-3 ~ h~ at-[:c©ineand the specizic displacers pirenzepzne (MI), /a~T)X-II6 (M2)~ IiHSiD (M3~, and u~labelecq IDE)I Results (mean _+ S}~): Saturatio~ Kd (pM) HiDDoc~uus Ce~bell-um Striatum

1-123 IDEX (n = 5) 28_+3.8 280 _+ 192 56 _+ 22

6_+4.0 54 -+ 8.7 54 + 17

Displac: Atropine Pirenzepine AFDX-I 16 HHSiD IDEX (n=2) InM) ~ n ; 1 - 5 ) n=2) (n=2) (n=2) 37.5_+3.8 61_+46.5 I0.9 _+ 4.0 3. 3_+0.5 1948_+601 14211+-14127 CB i. 4 460 _+14.8 69.2_+4.7 96.4 _+ 9.3 8.3_+1.6 ST 0.9_+0.2 51.7_+11.3 387 _+180 22.4 _+ 4.4 4. i_+0.i 3150_+2792

~

The Kd of 1-123 IDEX was lower than has in the literature_ Conside_rable.aspecific b inchlng of 1-123 u.~..was o~serve~ 'l~lerlr~tlnqs or the d/spAacemen~ ex~.nments are according to the lite.r@ture. The az-fi.m'~y of 1-123 IDEX ~ IDEX was slightly higher zor M,- ar~ MJ- ~nan zor ~z-receptors.

1311

either

KAKABAKO~ ~ , E. L IVANIOU ~ , G.P. EVANGELATOS ~, a n d D . S . ITHAKISSIQS ~,~

EYANGELAT~ ~ ,

~R/RP [nstltute, NCSR "Demokrltos", Athens 15310., Greece aDept of Pharmacy, Univ. of Patra$, Patras 26110, Greece SYNTHESIS OF PURE CONJUGATION LABELLING

IK]NO- AND

DI-

*2SI-TYRAIiINES

FOR

A method for preparing pure mono- and dl- ~ 2 ~ I tyramines is described. Tyramine was radioledinated according to the chloramine-T method, sllghtly modified. Briefly, 10 pL of tyramlne (0.73 mmol/L), 10 ~L of Na*mSl (250 CI/L in phosphate buffer 0.25 mcl/i, pH 7.5) and 5 ~L of chloramlne-T (3.55 ~ o l / L in phosphate buffer 0.25 mol/L, pH 7.5) solutions were incubated in a 3-mL test tube for 70 sec and then the reaction was stopped by adding 5 pL of a sodium metabisulfite solution (3.55 mmol/L in phosphate buffer 0.25 mel/L, pH 7.5). Mono- and dl- *asl-tyramines synthesized were isolated by thin-layer chromatography (n-butanol: 2 mol/L NH~OH: ethanol, 3:1:1, v/v/v) or paper electrophoresls (500 V, paper Whatman 3MM, barbital buffer 0 . 2 mol/L, pH 8 , 4 ) . The Rf values in the thinlayer chromatography system were: 0.36 (tyramine), 0.46 (mono-'2~I-tyramine), 0.52 (dl-~mSl-tyramine), 0.84 ('2sI); on the electrophoresls paper, non-, rmDno- and dl- ~=sl-tyramlnes were located 12, 5, and I cm, respectively, away from the origin, while free ~2sl had coI~pletely moved out of the strip. Under the conditions used, >95 % of the * = S l was incorporated into the tyramlne molecule and the relative percentages of monoand di- *cOl-derivatives synthesized were 90 % and 10 %, respectively. Pure mono- and dl- *esl-tyramines were finally obtained, with very high specific activities (2500 and 5000 Ci/Im~ol, respectively). These derivatives can be applied to numerous conjusation labellin 5 techniques, replacing the crude products used so far.

641

Tuesday, 3 September 1991

PO-3R1-25

PO-3R1-26

L.Fridrich, D.Szekeres, E.Artner-Dworzak, M.Havel, A. Gassnec, E.Harfiter, B.Puschendorf. Clinic For Nuclear Medicine, Dept. of Med. Chemistry and Biochemistry, Innsbruck, Dept. of Medical Chemistry University of Vienna, Austria

Modoni S . , Aucella F.,Guglielmi G,,Frusciante V., Guida C.C,,Petracea Ciavarella G.,Scarabino T.,Gramazio hi.L, Depts. of Nuclear Medicine, Nephrology and Radiology Hospital C,S.S., S.Giovanni Rotondo, Italia,

REST AND EXERCISE ANF- AND cGMP-PLASHALEVELS BY RIA ~[TH AND MITHOUT EXTRACTION IN COMPARISON TO RNV-EF. P]asma-Ocncenflrafiions of ANF and cGMP (its second messenger) can be assessed by RIA. However d i r e c t RIA o f ANF needs cumbersome p r e a n a l y f l i c b ] o o d - c o l l e c f i i o n , where-as cGMP can be assessed by RIA a f t e r E t h a n o l - E x t r a c t i o n From simple dra~n EDTA-Plasma. Therefore the aim o f t h i s study was to c o r r e l a t e in p a t i e n t s and healthy w~lunkeers EF-values during r e s t and exercise RNV with ANF and cGMP-levels in simultaneously drawn plasma-samples to judge i t s s u i t a b i l i t y For c l i n i c a l use. Results: in 36 p a t i e n t s with d i f f e r e n t heart diseases, i n c l u d i n g also p a t i e n t s a f t e r h e a r t - t r a n s p l a n f i a t i o n (n=16) a s i m i l a r c o r r e l a t i o n between ANF and cGMP o f r= 0,74 and r= 0,81 ( p e 0 , 0 0 1 ) could be demonstrated during r e s t and exercise r e s p e c f i i v l y . Excluding p a t i e n t s a f t e r heart t r a n s p l a n t a t i o n a negative c o r r e l a t i o n between r e s t i n g LVEF and ANF (r= 0,76, p ~ 0,001) and 6GHP (r= 0,58, p < 0 , 0 0 1 ) could be revealed. No c o r r e l a t i o n between eather plasmaconcentrations o f ANF oe cGBP was Found to I_VEF during exercise or to RVEF during rest and e x e r c i s e . However s i g n i f i c a n t d i f f e r e n c e s were demonsfirated t o t ANF and cGMP - l e v e l s between healthy v o l u n t e e r s and p a t i e n t s with heart diseases and between p a t i e n t s with and without h e a r t - t r a n s p l a n t a t i o n . Conclusions: normal resLing ANF and cGMP plasma-levels might exclude serious heart disease. Elevated l e v e l s o f ANF and eGMP must be i n t e r p e t e d wiLh care and need f u r t h e r i n v e s t i g a t i o n , cGMP seems more a p p l i c a b l e For broad c l i n i c a l use bee&use of ease in blood sampling.

RENAL OSTEODYSTROPHY: OSTEOCALCIN ASSAY vs ~ADIOLOGICAL FINDINGS.

(BGP)

~DIOI>~IUNO-

The Authors report their experience in the diagnosis of renal uremic ostheopathy, A study was carried out to evaluate the relationships between radiological findings vs. plasma Bone Gla Protein and other biochemical parameters in patients in routinar} dialysis treatment. 73 haemodialyzed patients (mean age 55±14 yrs.: dialytic age 56±36 mths) were studied by means of conventional radiology and hand microradioscopy (Meema method); in selected cases other imaging methods were used (CT, digital radiography, bone scintigraphy): CT densiLometry was performed in some typical cases. BGP RIA assay was carried out by a commercial kit (OSTK-PR, CIS International). PTH-C, alkaline phosphatase (ALP), calcium and phosphorus were also evaluated, All the patients were allowed to group A (hyperpsrathyroidism) or group B (osteomalacia), Student t test and linear regression were used for statistical analysis. High BGP levels were found in 68 pts, and correlated with PTH (p
PO-3R1-27

PO-3R1-28

A. P i f f a n e l l i , G. Giovannini, L. Catozzi, D. Pelizzcla, L. U c c e l l i , R. B a r o z z i , M. G i g a n t i . Chair of Nuclear Medicine, University of Ferrara (Italy)

J.M. RIEDINGER, C. TOUZERY, A. BERRIOLO, M. TOUBEAU, F. BRLrNOTTE Service de M6decine Nud6aire Centre G.-F. Lederc - 21034 DIJON CEDEX -FRANCE

RADIOMETRIC STANDARDIZED DETERMINATION OF EGFR: A PRELIMINARY EXPERIENCE IN QUALITY CONTROL. In the search for new biochemical tests for the

prognostic factors in mammary cancer, we focused our interest on the radiometric binding of Epidermal Growth Factor Receptor (EGFR). In the past f i v e years, many publications have been produced by several international groups, but =any discrepancies have emerged in the results. In collaboration with the EORTC Steroid Receptor Group, a new standardized method was performed and the main steps were: 1) adequate c e l l membrane preparation; 2) tracing of 1251-EGF by Protag 125 (Baker Chem., USA); 3) specific binding of 1251-EGF to membranes from mammary cancer; 4) method of separation by hydoxylapatite. A quality control was carried out in 1990 among 10 European Laboratories, on lyophilized human placenta (4 v i a l s = A,B,C,B). The results of the t r i a l were: 1) between-assay, expressed as coefficent of variation, was about 20%; 2) the mean of within-laboratory assay, by analyzing the same v i a l s (A=C; B=D), was about 22%. Experiments are now in progress for the determination of EGFR in human breast tumors accompanied by the assays of estrogen and progesterone receptors and oncogene c-erbB-2/neu a l l submitted to international quality control. Also, close follow-up of a larger series of patients a f t e r EGFR determination w i l l allow us to assess the oncological relevance of t h i s biochemical marker.

642

STUDY OF FT4 AND FT3 LEVELS DURING NORMAL EUTHYROID PREGNANCY The assessment of thyroid status during pregnancy is difficult because clinical signs can suggest thyrotoxicosis and assays of F~4 and FT3 are submitted to technical artefacts in relation to elevation of TBG levels. The aim of this study is to determine the evolution of serum levels during pregnancy and to select the best parameter to monitor thyroid status in pregnant women. Patients and methods : sera were obtained from a control group (N = 24) and from 58 clinically euthyroid pregnant women : 17 in the first, 18 in the second and 23 in the third trimester of the pregnancy. TSH was in the normal range in both group. FT4 and El'3 concentrations were respectively measured by two radioimmtmoassaTs : a one-step assay which uses a radiolabeled analog method Amerlex-M from AMERSHAM and a two-step immtmoextraction assay RIA-gnost from BEHRING. Results : PT4 level was found to be statistically lower when compared to the control group. This was observed in the three trimesters and with the two assays. PT4 level was strongly correlated to the age of pregnancy. In the third trimester FF4 was 38.9 % lower than the average of the control group (p < 0,001) and the concentration was in 34,5 % of the cases in the range of hypothyroidism. On the other hand, FI'3 level was 17.5 % lower in the third trimester (p < 0.001) and only 5 % of the patients were classified as hypothyroid. FT3 level was statistically correlated with the age of pregnancy but its relative decrease was lower than the relative decrease of El'4 during pregnancy. This finding is not dependent on the assay. Thus it seems more accurate to use F r 3 level to assess the thyroid status of pregnant women. Conclusion : When comparing to a non pregnant control group, FT3 reflects more accurately the euthyroid status of pregnant women.

Tuesday, 3 September 1991

-

Wednesday, 4 September 1991

PO-3R1-29

PO-3R1-30

M. Rodrigues, M.G. Paros and M.R. Vieira.

M.Kesse-Elia, E.Kaskani, Ph.Rondo~ianni, M.Maragou, l.Houssianakou, H.Giannopoulou, C.Alevizaki, P.Dantis. Depts of Nuclear Medicine, Rheumatology and Medical Physics, Evangelismoe Hospital, Athens ,Greece.

Nt~.lear i ~ i c i n e Depar~m~t, Institute Portugt~s de Oncologia Rim Prof I/ms I~sto, 1093 Lisbon, Portugal. SI~]M I~VEiS OF CA 125 IN DIMIkK~B~G, MINflDRh-~G D ~ EVALUATING PBJ£N]87S IN OVARIAN C A ~ .

ST#/US AND

.Most patients (pts) already have tumor spread throughout the peritoneal cavity when the diagnosis of ovari~n cancer is made. The sire of our study ~ s to determine the contribution of Ca 125 in the disgnosis and follow-up (nsmely in monitorieg disease status and in early detection of recurrence or metastasis) of ovarian carcinomes (OC).The prog_ nostic value of Ca 525 prior to therspy was also analysed. Serially ~e performed in 175 03 pts 447 serum RIA measurements of Ca125, for a period of 17.9 (3-57) months. Ca 12_5was elevated in all the 29 pts evaluated prior to therapy. Mean value of Ca 125 prior to therapy in pts with further favorable clinical course in follow-up was statistically different (p£O.Ol) from that of pts that showed signs of local disease or mo~stasis. All the 95 pta that ~re in remission in follow-up after initial therapy had normal levels of Ca 125. Twelve out of 63 pts that showed signs of disease were false negative for Ca 125~ Early increase of Ca 125 values were observed in 4 pts i-6 months before clinical and/or tadiological diagnosis of tumor reiapse. In conclusicn:1) We found e sensitivity of 100% at diagnosis of CC and 81% for detection of recurrent disease; 2) Increased levels of Ca 525 in follow-up most draw attention on the presence of local diseaseand/or metastasis; 3) Norm~l levels of Ca 125 during follow~p after initial the[spy do not guarantee s disease free condition; 4)Increased levels of Ca 125 can be the only positive finding, even before clinical snd/or radiological evidence of disease; 5) levels of Ca 125 prior to therapy have a prognostic value.

i

Wednesday, 4 September 1991 PO-4L1-1

PO-3R1-31 RUBELLO D,CASARA D,GIRELLI ME~SALADINI G,PICCOLO M~ BUSNARDO B~ Radiotherapy and Nuclear Medicine,

SERU~ TYPE III PROCOLLAGEN PEPTIDE LEVELS IN RHEUMATOID ARTHRITIS (RA) AND SYSTEMIC SCLEROSIS (SS). Serum levels of the aminoterminal type IIl procollagen peptide (SP-III-NP) have been used as a measure of collagen synthesis.The aim of this study was to estimate SP-III-NP levels (determined by RIA) in patients with RA and SS and correlate the findings with their clinical and laboratory data.Serum samples were obtained from 19 females with RA (mean ~ g e 56.4 ~i,9 yrs, mean disease duration 8,3 ± 1,9 yrs) and from 34 females with SS (mean age 55.8 i 1.9 yrs, mean disease duration 7.0 !1.2 yrs). Control sera were available on 21 healthy women of mean age 39.9 ±2,6 yrs.No correlation was found in controls between SP-III-NP and age.The results are as follows: RA (N=I9) SS (N=34) CONTROLS (N=21) SP-III-NP .725±,079 .741±.038 .497 ~.021 m v(U/ml) t ~ s ~ , ~<.ooi 'I [ J - - - p < .01 In RA there was a statistically significant positive linear correlation hetween SP-III-NP and rbc sedimentation rate (r= .667 p< .0025 ).SP-III-NP did not correlate with disease duration, Raynaud's phenomenon ,Ritchie index , lung involvement, Sjogren's syndrome, anemia and autoantibody, patterns.ln SS SP-III-N-P did correlate (r= .692 p< .001), esophageal with the disease activity involvement (r = .33 p< .05) and autoAb to SCL70 (r = .31 p< .033) There was a tendency for correlation with nucleolar Ah pattern and rheumatoid factor (p< ,06 for both). SP-III-NP did not correlate with the extend of cutaneous and organ involvement (except esophagus), disease duration and D penicillamine treatment. Conclusions:Patients with SS and RA had SP-III-NP levels higher than normals,oorrelating in SS with disease activity, esophageal involvement,and special autoAb patterns and in Rh patients with rbc sedimentation rate,

°Semeiotica Medics,

C. Alexander, R, Berberich, G. Omlor*, S, Schmidt Abt, f, Nuklearmedizin / Abt. f. Allgemeinchirurgie Universit~tskliniken; D-6650 Homburg/Saar; F.R.G,

University and Genera] Hospital of Padua, Italy. 'ROLE OF ANTI THYROGLOBULIN ANTIBODIES (TzAbs) ASSAY IN THE FOLLOW-UP OF PATIENTS WITH DIFFERENTIATED THYROID

3ANCER (DTC). rgAbs may interfere in Thyroglobu]in (Tg) assay and as consequence it ]imitates the usefulness of Tg as neoplastic marker.However,some authors recently reported that the presence of antithyroid Abs in patients (pts) previ~ usly treated for DTC may indicate the persistence of tumor (Pacini, Acta Endocrine1 1988,]19:$73). To further investigate this aspect,we studied TgAb changes in AS pts with DTC before and after thyroid ablation. They were 35 F,8 M,age ranged 18-65 yrs,mean 47. 33 pts had papillary, i0 follicular tumor.Following TNM classification 20 pts were classified T+NOMO, 19 N+MO, 4 M+. All pts were treated by total thyroidectomy,lSiI administration and hormonal therapy.Mean follow-up was 3.5 yrs. Tg and TgAbs were measured before surgery and then every 6-12 months.No relationship was found between preoperative TgAb levels and stage or outcome of disease. In 24 pts, considered tumor-free,TgAbs became undeteetable within 6-12 months from therapy. In 19 pts,TgAbs remained detectable:5 pts had persistence of disease,3 to nodes,2 to ]ungs.TgAbs were higher in pts with persistent disease than in tumor-free pts (653£196 vs 163~95 U/m],p < .01). Tg was elevated in only 2 pts M+. High TgAb levels in pts treated for DTO,even in absence of detectable Tg, may lead to suspect the presence of metastases. Yet,the disappearance of TgAbs seems to indicate the remission of disease.

MEASUREMENT OF BLOOD LEAKAGE DURING ISOLATED LIMB PERFUSION: A COMPARISONOF IN-ll3m TRANSFERRINE AND TC-99m BLOOD POOL LABELING In order to avoid complications a f t e r isolated hyperthermic limb perfusion the measurement of blood leakage from the extracorporeal to the systemic c i r c u i t is important. The present study tested Indium-ll3m transf e r r i n e as a potential substitute f o r Technetium-99m blood pool labeling. A group of 9 patients underwent i s o l a t i o n perfusion for the treatment of malignant melanoma of the upper/lower extremity in 2/7 cases. Four divided dosages of melphalan were injected in time inter~ vals of 15 minutes into the extracorporeal c i r c u i t . Ten minutes a f t e r in vivo labeling of red blood cells (RBC) with 150 MBq Tc-99m and the administration of 60 MBq In-ll3m the blood samples preceded every bolus and the last one was drawn 15 minutes a f t e r the last injection of melphalan, By the help of a mobile well counter the measurement of blood samples f o r Tc-99m- and In-ll3ma c t i v i t y was performed and the leakages were calculated i n t r a o p e r a t i v e l y , During perfusion t o t a l a c t i v i t y showed a mean decrease of 43.1±17.6 % (Tc) and 34.6+23,6 % (In) respectively, Leakage results are 0-20.1 (6.5+2.8) %(Tc) and 0-34.7 (12,0±2,5) % ( I n ) , The corresponding mean flow rates from the extracorporeal to the systemic c i r c u i t are 5,8±2.9 ml/min (Tc) and 10,9+2.2 ml/min ( I n ) , There was no correlation between the Teakage values of the two methods: y = 0,75 x + 6,19, r = 0.55, In conclusion In-ll3m t r a n s f e r r i n e is no releable substitute f o r Tc-99m blood pool labeling, The increased mean leakage results, probably caused by the low molecular weight of t r a n s f e r r i n e , overestimate the real melphalan leakage by far,

643

Wednesday, 4 September 1991

PO-4L1-2 PG Avery, H Williams, M Early, N Hudson, P J B Hubner. Regional Cardiac Unit, Groby Road Hospital, Leicester, UK.

EVALUATION OF CHANGES IN LV DIMENSIONS ON EXERCISE USING GATED MIBI S C I N T I G R A P H Y Left ventricular (LV) volume changes on exercise have been used to evaluate patients with coronary artery disease (CAD). We analysed changes in LV ~imensions from rest to exercise using gated T c - 9 9 m - m e t h o x y - i s o b u t y l - i s o n i t r i l e scintigraphy in 43 patients and compared the results with volumes calculated from radionuclide v e n t r i c u l o g r a p h y (RNV). The Correlation between resting end diastolic volume (EDV) and resting mean end diastolic diameter (EDD) was 0.777 (p~<0.001) and between resting end systolic diameter (ESD) 0.720 (p=<0.00I). On exercise this good correlation remained EDV versus EDD r=0.738 (p=<0.001), ESV versus ESD r=0.717 (p=<0.001). On exercise there was a fall in mean EDD from 19.52 to 18.14 (p=0.001) and a fall in ESD 13.99 to 11.25 (p=<0.001) in normals, while no significant change was found in EDD or ESD in those with CAD. This compared well with volume changes on RNV (EDV 156 to 138 p=<0.02 E S V 71 to 58 p=<0.02 in the normal group). Using failure to decrease ESD and/or an increase in EDD on exercise as diagnostic of CAD sensitivity was 79% and specificity 73%. Thus gated MIBI scanning provides a good indicator of changes in LV dimensions so enhancing its diagnostic usefulness in patients with CAD.

PO-4L1-3 H. Valette, L. Andre, M.H. Bourouionon, P. Merlet and A. Syrota. SHFJ-CEA, Orsay and CHU Paris XI, France.

LEFT VENTRICULAR SIZE MEASURED ON TL-201 SPECT GIVES INFORMATIONS ON THE SEVERITY OF CORONARY ARTERY DISEASE. The dilatation of LV cavity is an adaptative response of myocardium. LV size estimated from SPECT could become a useful clinical parameter. Eighty two patients with, or without, coronary artery disease (CAD) were studied after exercise (Ex) and at rest (R) : group 1 (n=26) with a low likelihood of CAD, group 2 (n=30) with a previous myocardial infarction and group 3 (n=26) with angina pectoris. LV size was obtained as the size of Endo- and epicardial (Epi) ROIs automatically drawn on 5 thick (2pixels) short axis tomographic slices (SATS) ; the myocardial ring was calculated as the difference between Endo and Epi ROIs. TI-201 redistribution was quantified on bull's eye images obtained from SATS. LV ventricular function was estimated with radionuclide ejection fraction (LVEF). Results: Sizes of Ex-Endo, Ex-Epi, R-Epi, Ex-ring and R-ring ROIs were significantly different in the 3 groups of patients (p<0.01). R-Endo ROI sizes were not different in groups 1 and 3. Ex-Endo, Ex-Epi and Ex-Ring ROI sizes significantly correlated with LVEF (r= 0.8, r= 0.87, r= 0.84 respectively). A decrease in ring size from Ex to R was observed in group 3 but this decrease was not correlated with the presence of TI redistribution; in the 2 other groups, the ring size remained unchanged. Conclusior]; a large LV size is associated with severe CAD. Since changes in LV size could not be related to ischemia assessed from TI redistribution, the measurement of Ex LV size can give an additional prognosis information about the severity of CAD.

PO-4L1-4

PO-4L1-5

I.¢arri6, M.Estorch, L.Bern&, C.Duncker, G.Torres, D.Duncker. H o s p i t a l de Sant Pau, Barcelona. Spain.

M.Clausen, E.Henze, J.Langhans, V.M~ller, R.Weller, J.Mester (i), S.Mack, M.Kochs, T.Eggeling, W.E.Adam Nuclear Medicine, Cardiology~ University Ulm~ Germany (i) Nuclear Medicine, University of Szeged, Ungarn

CUMULATIVE DOSE OF DOXORUBICIN AND SEVERITY OF MYOCARDIAL DAMAGE ASSESSED BY ANTIMYOSIN MONOCLONAL ANTIBODY STUDIES.

FREQUENCY AND POSITIVE PREDICITVE VALUES FOR TYPICAL ARTEFACT-LIKE LESIONS IN COLOR-CODED POLAR QUANTIFICATION OF MYOCARDIAL SPECT.

To assess chemotherapeutically induced myocardial damage, we performed In-111 antimyosin antibody scans and ejection fraction measurements in 34 c a n c e r p a t i e n t s who had received chemotherapy including d o x o r u b i e i n , A n t i m y o s i n u p t a k e was q u a n t i f i e d by means o f a h e a r t t o lung r a t i o . Of 8 p a t i e n t s s t u d i e d a t a c u m u l a t i v e dose o f 200-300 mg/mz o f d o x o r u b i c i n , antimyosin u p t a k e in t h e myocardium was o b s e r v e d in 5 patients; h e a r t t o lung r a t i o in t h i s group was 1 . 6 4 ± 0 . 1 2 (p
In myocardial SPECT polar quantification is limited by a high rate of false positive results. The purpose of the study is to define patterns~ determine their frequency, and the positive predictive values for typical artefact,-like lesions in the polar plot. In 270 angi0graphically controlled myocardial SPECT 26 polar lesions are not explained by the anglo finding. The patterns of these false positives are: sectorial at 2 hour (N=I8); peripheral (N=2); inferior (N=IS); circumscribed apical (N=22); irregular widespread (N=5); hot spot (N=4); anteroseptal (N=4). The following statistics incorporates the frequency of angiographically proven lesions with identical pattern. The sensitivity (sens) and specificity (spec) is calculated: for all lesions patterns (all), for artefactlike lesions only (arte), for all except arte lesions (no arte), for all lesions including visual analysis of the slices (+slices). The positive predicitive val (+PV) is calculated for a prevalence of 50%. sens spez +PW all: 88.8% 52.7% 65.5% arte: 28,4% 52,7% 37.4% no arte: 60.4% I00 % I00 % all+slices: 88.8% 60.0% 80.6% Characteristically the polar plot exhibits a high sensitivity and a rather low specificity. By taking the lesion pattern into account the +PV may be dramatically differentiated: in artefact-like lesion the +PV is reduced to one-third, while in all other patterns the +PV will approach 100%. In any case, for final diagnosis a careful reading of the original data (short and long axis slices) will remain dominant.

644

W e d n e s d a y , 4 S e p t e m b e r 1991

PO-4L1-6 J.Dalle Mule. G.Soravia, A.DaPo!d. P.Peltegrini *R Perslli, ~:F.Martinelli, ~B.Sponga, ***C.Burelli, :~:~*D.Zanuttini. UCI - 5ervizio di Cardiologia; ~'Servizio di Medicina Nueleare O.C. Belhmo, Bellun{ ***Dbisione di Cardiologia, O.C.Pordenone, Pordenone, ITALY. T H E INFLUENCE OF THROMBOI,YTIC THERAPY FOR ACLVfE MYOCARDIAL INFARCTION W I T H OR W I T I t O U T PTCA ON EXERCISE 20 I - T H A L L I U M SCINTIGRAPItY. The aim of the present study was to determine the impact of residual coronaD" artely stenosis after thrombolyrie therapy and PTCA of the infarct related vessel on maximal 3PECT 201-ThalIium exercise peffusion scintigraphy. We studied 7:t consecutive patients who received i,v. thrombolysis for an acute myocardial infarction and were submitted to coronary angiography within -/- wee!
positive locatgdn stenosis therapy (h) negative location stenosis therapy adm.

(n:28) (22%) (50%) 43% 2.9 2.2 22 {78%) 12 (57%) 39% (h) 2.9 3.6 6 3

(n:44) (53%) (65%) 95% 3.7 1.7 2] (47%) 15 (70%) 72% 3.3 0.2

23 15

PO-4L1-7 ~ w R. Roszczyk, W. Wysznacka-Aleksandrow, J. Wnuk, iek, P. Borkowski, E. Szwiertnia-Roszczyk, S. Bojenko. Central Clinical Hospital WAM, Warsaw, Poland. GATED RADIOISOTOPE ANGIOCARDIOGRAPHY (GRA) FOR THE ESTIMATION OF THE LEFT VENTRICLE FUNCTION DURING FAST TRANSESOPHAGEAL PACING OF THE LEFT ATRIUM GRA has been performed In 16 persons without Coronary Artery Disease (CAD) and 21 patients with CAD (narrowing ,)70Y, or a total occlusion of one coronary artery}. Systolic and diastolic parameters before, during, and after fast transesophageal pacing of the left artrium were measured. AFTER REST normal

CAD El; PI~P. tPER

TE PFR tPFR

TF *

PACING normal

CAD

6SJ +-n.9 4e.~ + 14.e 1~.9 + iS.@ 2,3 +0.s 3.1 +-0.9 t.~ ± o . s t.~ ¢ 0 .S 24.9 +4.,5 33.6 +5.9 ss.s-+ s.8 a2.8.+6.z 61.3 "1-4.2 4S.3 -+6.3 4s.4 -+4.s 8S.0+~.8 61.6 "+10.6

1.9 -+0.7

1.~*o.~

18.6 4"-6.0

12.s +-e.l

54.7 "+6,2

se.st ~.v

PACING normal

7.1 -+3°| 4.:l+ 2.6 22.0 "+4.5 25.6+-5.= 38.7 +-4.1 17.0.+ ~'.l

C~kD

60.2 -+9.4 48.8+U.l 2.5 -+o.7 2.1+0.9 26.3 -+6.! ;=1.~-+ 8.1 81.3 -~.6 82.8-+~.2 3.0 -+1.3 Z.5 -+1.3

23.7 -+6.8

2 6 . 8 +- 9 . 8

48.7 -+7.5

In conclusion PTCA is associated with a significant reduction of the residual stenosis and provocable isehemia in the IS. Furthermore, there is an improvement of the infarcted RWM$ after PTC_<

During pacing, in patients without CAD, a si nificant increase of EF, PER, tPER, TE, PFR, TF was obserwed accompanied by akinesis or dyskinesis of the left ventricle. In patients with CAD, the results differed significantly from those without CAD, both a decrease In EF and aklnesie or dyskinesis were observed in the course of pacing. It has been concluded that the fast esophegeal pacing of the left atrium in the GRA is a valuable dl~jnostlc for coronary artery disease.

PO-4L1-8

PO-4L1-9

D. Faaret. J.E. Wolf, E. B o r r e l , C. R o c c a , J. Machecourt, M. Comet. Services de M6decine Nucl~aire et de C a r d i o l o g i e LERU R A CNRS 1287 - GRENOBLE FRANCE

M.Faraggi ° , G.Montalescot °° , G.Drobinski °° B.Mazoyer °°° , O.Messian ~ , A . S y r o t a ° ° ° B . B o k ° ' D.Thomas ° Y.Gresgogeat°°: °Beaujon (Cliehy);°°Salp~tri@re(Paris); °°°Serv. Hosp. F.Joliet (CEA,Orsay) -FRANCE.

*

]23I-SMIHA-SPECT DETECTION OF VIABLE TISSUE IN M Y O C A R D I A L SEGMENTS WITH P E R S I S T E N T D E F E C T S AT TL 201 SPECT, IN P A T I E N T S WITH A FIRT Q WAVES M Y O C A R D I A L INFARCTION. TO assess the p o s s i b i l i t y to detect viable m y o c a r d i u m in segments with p e r s i s t e n t d e f e c t s at 2 0 1 T I - S P E C T , with ]23I-~MIHA ( 1 6 - i o d o - 3 - m e t h y l h e x a d e c a n o i c - a c i d , a new r a d i o - l a b e l l e d fatty acid, 30 p a t i e n t s (29 M, 1 F, 56,5±8.5 y.o) were p r o s p e c t i v e l y s t u d i e d b e t w e e n the 2nd and the 6th week f o l l o w i n g the o n s e t of a first acute Q waves m y o c a r d i a l infarction (MI). A l l of t h e m benefit of : stress 2 0 1 T I - S P E C T (3 m C i I.V. at the p e a k of e x e r c i s e , initial study and d e l a y e d study 4 hours later were p e r f o r m e d ) , stress 123I-~MIHA-SPECT (4 mCi I.V. at the peak of e x e r c i s e ; i n i t i a l study and d e l a y e d 40 m i n l a t e r ) ; c o r o n a r y a n g i o g r a p h y and left v e n t r i c u l o g r a p h y . F o r b o t h SPECT, short axis, sagittal and coronal images were reconstructed. The left v e n t r i c u l a r m y o c a r d i u m was d i v i d e d in 9 segments (sgts) to compare 201 T I - S P E C T with 1231~ M I H A - S P E C T , and in 5 sgte (apical, anterior, eeptal, lateral, inferior) to c o m p a r e b o t h S P E C T w i t h left v e n t r i c u l o g r a p h y . Of t h e 270 sgte a n a l y s e d on 201 TI-SPECT, 75 had fixed d e f e c t s (F), 24 r e v e r s i b l e d e f e c t s (R) and 171 were n o r m a l (N). 5 M I H A fixation (initial and/or delayed) was o b s e r v e d in 36 (48%) of the F sgte, in 23 (95.8%) of the R egta and in 169 (98.8%) of the N sgts.On the 150 sgts a n a l y s e d of left v e n t r i c u l o g r a p h y 25 were d y s k i n e t i c or a k i n e t i c (A). P r e s e r v e d f i x a t i o n of 2 0 1 T I was observed in 4 (16%) A sgte, ~MIBA fixation was o b s e r v e d in Ii (44%) of A sgts. To conclude, 1 2 3 1 - 5 M I H A a p p e a r s to be u s e f u l l to d e t e c t viable m y o c a r d i u m in the area of a p e r s i s t e n t defect at 201 T I - S P E C T in p a t i e n t w i t h a first m y o c a r d i a l infarction.

LATE PTCA IN ASYMPTOMATIC PATIENTS WITH M Y O C A R D I A L INFARCTION (MI) AND NO EVIDENCE OF RESIDUAL ISCHFA~IA : MYOCARDIAL V I A B I L I T Y DEMONSTRATED BY REPEATED T H A L L I U M SPECT. To demonstrate wether myocardial viability exists after a Q-wave MI in asymptomatic patients without clinical and scintigraphic evidence of residual isshemia, 15 patients (pts) with one vessel disease (7 left anterior descending arteries, 8 right coronaries) and MI older than 6 weeks were randomized for medical treatment or PTCA. Stress TI-BPECT was performed before randomization and repeated 2 months later. TI uptake was estimated by a normal/pathological counts ratio (automatic Bull's Eye analysis). TI uptake improved significantly in the PTCA group (ratio decreased from 1.97 to 1.72, decrement = .25 ± .2, n:8, p
645

Wednesday, 4 September 1991

PO-4L1-lO

PO-4L1-11

M. F i t z s i m o n s , D. H a m i l t o n , D.D. Kidney, P.J. Freyne, J.F. Malone, P. C r e a n and M. Walsh. St. J a m e s ' s Hospital, D u b l i n 8, Ireland.

P,R.Franken, R.Ranquin, A.Dobbefeir, J.Vandevivere. Middelheim Generat Hospital, Antwerp (BELGIUM).

M Y O C A R D I A L P E R F U S I O N IMAGING: T H E E F F E C T S OF RADIONUCLIDE, DATA REPRESENTATION AND I N T E R A C T I O N W I T H THE IMAGE. T h i s s t u d y w a s u n d e r t a k e n to a s s e s s the e f f e c t s of the c h o i c e of r a d i o n u c l i d e , image r e p r e s e n t a t i o n t e c h n i q u e and i m a g e d i s p l a y m e d i u m on the d i a g n o s t i c p r o c e s s of i n t e r p r e t i n g m y o c a r d i a l p e r f u s i o n images. The factors studied were data acquisition using T I - 2 O I or Tc-99m, image p r e s e n t a t i o n u s i n g h a r d c e p y or i n t e r a c t i v e c o m p u t e r d i s p l a y , and image r e p r e s e n t a t i o n u s i n g c o n v e n t i o n a l longand s h o r t - a x i s or 3D s u r f a c e display. 75 patients with suspected coronary artery disease were investigated prospectively. All u n d e r w e n t c o r o n a r y a r t e r i o g r a p h y and S P E C T i m a g i n g w i t h i n an e x a m i n a t i o n i n t e r v a l of less than one month. The i n v e s t i g a t i o n s w e r e read b y b o t h R a d i o l o g i s t s and C a r d i o l o g i s t s and the r e s u l t s w e r e e v a l u a t e d u s i n g ROC curve analysis. T h e s e r e s u l t s i n d i c a t e that: T c 9 9 m M I B I is m o r e s e n s i t i v e than T I 2 O I in the d i a g n o s i s of CAD, the d i a g n o s t i c p r o c e s s is i m p r o v e d w h e n the i n t e r a c t i v e c o m p u t e r d i s p l a y o f f e r s m o r e t h a n the static images d i s p l a y e d on h a r d c o p y and 3D i m a g e r e p r e s e n t a t i o n b e n e f i t s the less e x p e r i e n c e d observers.

DETECTION OF MULTIVESSEL DISEASE AFTER ACUTE MYOCARDIAL INFARCTION WITH Tc99m SESTAMIBI. To identify patients (pts) with multivessel disease (MVD) after acute myocardial infarction (AMI) combined first pass radionuclide angiocardiography (RNA) and SPECT using Tc99m SESTAMIBI were obtained, as well as ECG, at rest and at peak exercise 13_+4days after acute event in 43 pts. Eighteen pts had MVD (_>70% stenosis) on coronary angiography (CA) obtained within 5 days of the radionuclide tests. Positive exercise ECG, >5 EF-units decrease in LVEF or exercise induced ischemia on SPECT were respectively observed in 6, 12 and 15 pts with MVD. All pts with MVD had at least one positive test for exercise induced ischemia, Exercise induced ischemia was also noted in 13/25 pts with single vessel disease (SVD). No significant differences were noted between SVD and MVD in perfusion severity score, LVEF or ST segment depression. Localisation of exercise induced ischemia in the infarcted or in remote regions on RNA and SPECT studies; CA

AMI

n

MVD ANT 7 INF 11 SVD ANT 12 INF t3

WALL MOTION PERFUSION INFARCTED REMOTE INFARCTED REMOTE 4 2 4 2 2 4 0 9 3 4 6 1 2 1 5 1

Conclusion: (1) all pts with MVD after AMI were detected by combined exercise RNA and SPECT; (2) ischemia is not related to the extent of coronary artery disease (3) SPECT identified MVD after INF but not after ANT MI; (4) peri-infarction zones at risk are frequent after acute MI.

PO-4L1-12

PO-4L1-13

Institute of Gardiology and Cardiovascular Surger~ 17 y A, Vedado~ Habana, Cub~ LATISSIMUS DORSI CARDIOMYOPLASTY: ASSESSMENT CARDIAC EQUILIBRIUM GA~EDANGIOGRAPHY

BY

I~tissimus dorsi cardiomyoplasty was performed in eight patients with dilated cardiomyopathy, normal coronary arteries aad functional mitzal regurgitation graded as severe or moderate, Patients were studied by equilibrium gated anglography one week before surgery and four months later. The functional mitral regurgitatlon was assessed by the ventricularamplitude ratio (VAR) derived from the Pourier image. The clinical status of the patients improved from the NYHA functional class III or IV to the class I or If. There was no clinical differences in the pra and postoperative left ventricular ejection fraction (EF). Nevertheless, the postoperative end diastolic volume index was 74 ± 11% of the preoperative value and the VAR decreased from 2.01 ± 0.54 to 1.21 ± 0.59. Our results indicate that in patients with severely depressed myocardial contractility the main effect of dynamic cardiomyoplasty is the reduction in the left ventricular diameters. Secondary to this effect, the functional mitral regurgitation was reduced and the cardiac performance improved, although the E ~ w a s not modified,

646

W. Furlan~ H. Fritzsche~ E. Hillbrand, W. Benzer. Departmsnts of Nuclear Medicine and Internal Medicine, Landeekrankenhaus~ Feldkirch, Austria.

RESULTS OF REINJECTION STUDIES WITH TL-201 AFTER MYOCARDIAL SCINIIGRAPHY IN AN UNSELECTED PATIENT GROUP. Reinjection oF T1-201 after stress/redistribution myocardial seintigraphy was reported probably to evaluate viable myocardium £n persistent defects. Expected frequency for reinjection studies in an unselected patient group with suspicious coronary artery disease (CAD) or myocardial infarction (HI) remains to be assessed. During the period from 1.7 to 31.12.1990 we performed 513 TI-201 stress/redistribution myocardial scintigraphies for evaluation of CAD and MI. In IOQ of these patients (n= 51; 39 m~ 12 f; 35-78 a; ~= 59 a) a persistant T1-201 defect was observed and a reinjection study was performed. 18 of these pat. were referred to seintigrsphy because of suspicious CAD, 33 pat. because of MI. 28 pat. (35%) showed a persistant defect, 23 pat. (45%) s "fill-in" phenomenon. Quantification of "fill-in" phenomenon was assessed by calculation of the percentage of maximum T1-201 activity in the defect area in 24 pat.

The percentage showed an increase in 8 pat, (~= +22~) with " f i l l - i n " phenomenon and remained equal or decreased (~= -12%) in 16 pat. with scars. In 6 of 7 pat. with " f i l l - i n " phenomenon coronary arteriography showed stenoses~< 100%. In 3 patients with soars coronary arteriogrsphy revealed 100% stenosis and stenosis<10O~ in 5 patients. Our results indicate a condiserable number of patients with suspicious CAD or HI showlng " f i l l - i n " phenomenon in r e i n j e c t i o n studies who may benefit from more extensive treatment.

Wednesday, 4 September 1991

PO-4L1-14

PO-4L1-15

DG Gordon, M Lyle, A Saalmann, SJ Schultz, SL Pellerin, L Belardinelli. Memorial PETscan Center, Jacksonville, FL and University of Florida, Gainesville, FL.

DG Gordon, SJ Schultz, and SL Pellerin. PETscan Center, Jacksonville, FL.

COMPARISON OF THE VASODILATORY ACTION OF IV ADENOSINE AND DIPYRIDAMOLE IN THE SAME PATIENTS USING PET SCANNING OF THE HEART. Ten Pts. underwent PET myocardial perfusion imaging of the heart using the ultra short-lived radicnuclide Rubidium-82 (Rb-82), which allowed for serial studies in the same Pts. After obtaining a resting Rb-82 study, each Pt. was infused with 140 mcg/kg/min of adenosine (A) for 6 min. Hand grip stress was applied for the middle 4 min. Rb-82 was infused halfway through the A infusion period. All side effects abated within 5 min. After a 20 min. wait, the Pts. were infused with 142 mcg/kg/min of dipyridamole (D) over 4 min. and after a 2 min. wait, hand grip stress was applied for 4 min. Rb-82 was infused halfway through the hand grip stress. Blood pressure and heart rate increased in all subjects with no statisticall~ significant differences between A and D. Computer analysis of the data allowed the calculation of the average percentage difference in coronary blood flow between rest and stress for the ehtire left ventricular myocardium. This value was 133% for A (range 112-154) and 147% for D (range iii-168), which was not a significant difference. The ratio of intensity of the stress studies of A to the stress studies of D showed an average value of 92% (range 78-101). Side effects such as chest pain, headachet and shortness of breath were similar in both cases, but in general more intense with A. Transient heart block occurred with A in 1 Pt. Four Pts. preferred A, 4 D, and 2 had no opinion. We conclude that A and D given intravenously provide equivalent increase in coronary blood flow in the same Pts. Side effects were similar, although in general more intense with A. There was no particular Pt. preference.

SAFETY OF THE USE OF INTRAVENOUS DIPYRIDAMOLE IN MYOCARDIAL PERFUSION IMAGING: A FIVE YEAR EXPERIENCE. Between Sept. i, 1985 to Dee. 31, 1990, one of the authors (DGG) has supervised the administration of IV dipyridamole to 2576 Pts. for the purpose of producing increased coronary blood flow for myocardial perfusion imaging. 35% were done using SPECT thallium imaging and 65% were done using PET Rubidium-82 scanning of the heart. The dosage was 0.56mg/kg injected over 4 minutes. Untoward rea£tions were as follows: none-22% of all Pts., mild-57%, moderate-20%, severe-l%. The most common symptoms were headache (44%), chest pain (31%), dizziness (i0%), epigastric discomfort (7%)i neck, jaw, arm and shoulder pain (7%}, nausea, (6%)t shortness of breath (5%), leg discomfort (5%), and other minor reactions less than 5%. ST depression occurred in 16%, PVC's in 2%, and PAC's in 0.4%. Delayed reactions of joint soreness occurred in 2 Pts. and nausea in i. Reactions of special concern were marked hypotension in 9 Pts., bradycardia in 2, a vasovagal reaction in i, acute respiratory distress in i, severe wheezing in 2, and vomiting in i. One nonfatal myocardial infarction occurred within 1 hour after the procedure (0.03%). Several cases of angina pectoris were prolonged for as long as 15 min. The first line of defense in treating severe reactions is intravenous aminophylline in a dose of 125 mg given over 2 min. Sometimes 2 or 3 doses are required. We have had no problems with significant arrhythmias using these doses. All reactions to dipyridamole, except the myocardial infarction, have been immediately reversible or self-limited. There have been no deaths. We conclude that intravenous dipyridamole used over a long period of time has been found to be a safe method of producing increased coronary blood flow for myocardial perfusion imaging.

PO-4L1-16

PO-4L1-17

C. GRANDIN, A. BOL, A. COPPENS, B. ESSAMRI, F. HAMMER, W. WIJNS, J. MELIN. University Louvain-la-Neuve and Brussels, Belgium.

R. DEMEURE, of Louvaln,

Mltl DETERMINATION OF MYOCARDIAL CONTOURS FOR PARTIAL VOLUME AND SPILLOVER CORRECTIONS OF PET DATA. In order to correct PET cardiac data for finite resolution effects, we have developed a correction method based on a Monte Carlo simulation. This requires an accurate delineation of the heart contours. The contours are usually obtained from PET images and therefore submitted to errors. In this study, we compared PET and MRI defined myocardial thickness and contours in 26 coronary patients. We also evaluated the effect of these parameters on the quantified PET results. On 210 regions of interest (ROIs), the difference between PET and MRI thickness was within a range of ± 30% in 75% of the ROls. In absolute values, 75~ of the ROIs were in a range of ± 3mm. We selected the cases which showed a difference of + 30% and -30~ and we used the MRI contours to evaluate the spillover and the partial volume effects. We calculated the value of metabolic rate of glucose (MRGIu), acetate kinetics (T~) and absolute blood flow (NH4) obtained with the contours delineated by PET and MRI, respectively. If PET overestimated wall thickness, it underestimated MRGIu from maximum 15% and inversely. The effect on acetate T~ was less than 5%. For NH4, an overestimated wall thickness gave an overevaluation of flow of maximum 15~ and inversely. We conclude that the difference between myocardial PET and MRI contours was >30% in only 25% of the analyzed ROls. The influence of a 30% difference was maximum 15% on MRGIu and flow and less than 5Z for acetate kinetics.

Memorial

M. Gv6ngy6si, H. Klepzig, F. D. Maul, R. Standke, D. Mildenberger, G. Hfr, M. Kaltenbaeh. Divisions of Cardiology and Nuclear Medicine, University Medical Center, Frankfurt/Main CHRONIC CORONARY ARTERY OCCLUSION VS STENOSIS: PRE-/POST-PTCA STUDIES UTILIZING TC99M-SESTAMIBI MYOCARDIAL SCINTIGRAPHY The aim of our study was to evaluate whether the re-opening of a chronically occluded vessel leads to a comparable improvement of perfusion as successful PTCA, either at rest or dufin~ exercise-induced transient ischemia. 27 paUents (pts) with CAD, 16 pts with critical stenosis, and 11 vath chronic occlusion (5 without transmural myocardium infarc0 were studied within 1 week before and after successful PTCA utilizing quantitative myocardial SPECT. A 1-day Tc-99m-Sestamibi protocol was applied. After reconstruction and reorientation, sectofial profiles of 4 slices (short axis) covering the entire myocardium were generated. Differences between two profiles were calculated as an index derived from the sum of sectorial uptake differences (SUD). Perfusion defects at rest were calculated as difference between a normal sectorial and a patient profile; a perfusion defect during exercise as the difference between rest and exercise profile. Interestingly, pts with total occlusions had a more severe exercise-induced myocardial ischemia (436 vs 187) and less perfusion defects at rest (203 vs 334) than pts with coronary stenoses. After successful PTCA, both groups indicated a significant reduction of exercise-induced ischemia (p<0 05). Perfusion at rest was significantly improved (SUD >50) in 36% of pts with prewous stenosls and m 36% of pts with previous occlusion, respectively. In conclusion_, our results indicate that both groups benefit significantly from coronary intervention. However, and this has not yet been shown, differences were found before PTCA: ischaemia is more pronounced at rest in pts suffer!rig from stenosis, whereas pts suffering from chronic occlusxon present with prevailing ischemia during .exercise.

647

Wednesday, 4 September 1991

PO-4L1-18

PO-4L1-19

B.Haubold-Reuter, R.Ha±oemann, F.Amann, J.Turina, W.Reist, K.Leenders, G.K.v. Schulthess Klinik u. Poliklinik fur Nuklearmedizin, Dept. Med. Radiologie., Kardiologie,Dept. Int.Medizin, //SZ z~r4ch, B/i~Villlgen: CH

M.J.Henzlova, v. Bittner, E.Dubovsky, H.Nath, University of Alabama at Birmingham Medical Center and V.A. Medical Center, Birmingham, AL, USA.

P O S I T R O N EMISSION T O M O G R A P H Y IN A S S E S S M E N T OF THE METABOLIC STATE OF THE HEART MUSCLE In some states of the m y o c a r d i u m in w h i c h conventional diagnostic methods s u g g e s t the p r e s e n c e of m y o c a r d i a l infarction, t h e r e is persistent metabolically active myocardial tissue. One of these states is the "hibernating myocardium". Patients with this disease e n t i t y will show an improvement in c a r d i a c f u n c t i o n after revascularisation in over 85 %. Therefore the diagnosis of "hibernating myocardium" has a high predictive value. Purpose of study: Differentiation between e s t a b l i s h e d m y o c a r d i a l infarction and " h i b e r n a t i n g myocardium" by positron emission tomography by combining imaging of myocardial m e t a b o l i s m with imaging of myocardial perfusions. Method: 36 p a t i e n t s with e s t a b l i s h e d m y o c a r d i a l i n f a r c t i o n and a question of "hibernating myocardium" have been examined in the PET scanner at the Paul Scherrer Institut (PSI). Images of g l u c o s e metabolism were made by using 18fluorodeoxyglucose, and p e r f u s i o n images were obtained using thallium in a first phase (Thallium-SPECT) and Rubidium-82 as a p o s i t r o n emitter in a second phase. Results: In 19 of 36 patients, that is in 53 %, we i d e n t i f i e d "hibernating myocardium" Conclusion: Our study confirms that "hibernating myocardium" is relatively frequent in a selected population of patients with myocardial infarction.

HIGH INCIDENCE OF STRESS-INDUCED THALLIUM-201 MYocARDIAL PERFUSION DEFECTS IN PATIENTS WITH PATENT INTERNAL MAMMARY TO LEFT A N T E R I O R DESCENDING ARTERY GRAFT. Twenty consecutive symptomatic patients (15 men, 5 women) underwent symptom-limited exercise (n=17) or dipyridamole (n=3) thallium-201 imaging and coronary angiography 30.5±21.2 months after coronary revascularization with an internal m a m m a r y artery graft (IMA). Two patients with distal IMA stenoses developed stress-induced ischemia in the proximal and distal left anterior descending artery (LAD) distribution. Of 18 patients with patent, non-obstructed IMA, 13

(72%) developed reversible perfusion defects with stress: 6 in proximal, 4 in distal, 3 in both proximal and distal LAD distributions. Proximal LAD occlusion and/or distal LAD stenosis were evenly distributed in patients with and without stress-induced isehemia in the LAD territory. The unexpectedly high incidence of stress-induced perfusion defects in nonstenetic IMA may be related

to limited IMA flow during stress.

PO-4L1-20

PO-4L1-21

S. Iles, L. Lalonde, A. Fung, R. Burns, R. Nickerson, P. Radzikowski, L. Diagneault, F. Hong Tai Eng. Victoria General Hospital, Halifax, Nova Scotia, Canada.

L Bontemps, R Itti, F Delahaye, O Jegaden, P Mikaeloff Cardiological Hospital, 69003 Lyon - France

EXERCISE TC-99MTEBOROXIMECARDIAC SPECT: OPTIMIZATION OF ACQUISITION PARAME±E~S. Exorcise Tc-99m-teboroxime (TEBO)SPECT was performed and compared to exercise TI-201 SPECT in 25 patients, 14 of whom had cardiac eath within 3 months. Rest and stress TEBO images were acquired Within 2 min. of injection of 15-25mCi TEBO on a GE Starport 400 A. using step-andshoot, 32 stops from -135 ° 120 to 450 RAO. 12 sees (18 pts), 9 sees (4 pts) or 6 sees (3 pts) per stopwereused for total imaging times of 540,440,and 354 sec. respectively. TI-201 studies were performed within 2 wks, using 3 mCi of TI-201. 3 blinded readers analyzed 9 segments per study as normal(N), reversible(R) or fixed(I). Coronary artery disease was defined a s > 7 0 % narrowing of primary or major secondary branches. Exact agreement between TI-201 and TEBO occurred in 160/225 segments (71%). CAD in primary coronary territories (LAD, circ., RCA) was detected with sensitivity of 77% (17/22) and 73% (16/22) and specificity of 70% (14/20) and 75% (15/20) for TI-201 and TEBOrespectively. Exact agreement was present between segmental TEBO and TI-201 scores in 76% (48/63) for short (6 or 9 sec) acquisitions and 69% (112/162) for 12 sec acquisitions (see tables). TI-201 TI-201

EVOLUTION OF STRESS EJECTION FRACTION IN PATIENTS WITH SEVERELY REDUCED LEFF VENTRICULAR FUNCTION BEFORE AND AFTER CARDIOMYOPLASTY. In order to assess the benefit of cardiomyoplasty (technique of Carpentier and Chachques) stress blood pool studies have been performed before surgery and at regular intervals during the follow-up. The population included 12 male patients (age=59.3 +/-7.1 years) suffering from severe congestive heart failure (NYHA class III). With exception for 2 patients (one received a heart transplant 8 months after cardiomyoplasty and another one is on a waiting list) all patients are clinically improved (NYHA class I or II). In a subgroup of 9 patients for whom the 6 month follow-up tests have been completed, the radioisotopic results are as follows : resting EF stress EF Preoperative 17.7+/-8.1% 16.8+/7.3% 6 month follow-up 15.4+/-2.8% 17.3+/-4.9% Despite the absence of significant changes in ejection fraction, the maximal stress levels reached were statistically higher after surgery (p < 0.05): preoperative workload W = 49 +/-30 watts (2 patients could not perform any exercise : W=0) and 6 month follow-up W=81+/-20 watts (all patients could exercise at least at 50 watts). The obvious clinical and functionnal improvements of patients with initial low ventricular performance are therefore not supported by relevant changes in rest nor stress ejection fraction values.

TEBO (6 or

-N

36

7

1

TEBO (12

-N 95

16

7

9 sec)

R

3

12

0

sec)

R

5

i0

5

I --

0

4

0

I --

7

i0

7

63

l-l_ -~_ 162

Preliminary results suggest bettor agreement between TI-201 and teberoxime for shorter acquisition times.

648

Wednesday, 4 September 1991

PO-4L1-22

PO-4L1-23

JM Latre, FM Gonz~lez, A Jim~nez-Heffernan, JM Arizbn(~) M Tortes, A Valverde, JM Llamas and A Mated

!i.]:[. KeG, K.S. Hsieh, Y.L. Wang, C.W. Chen, S.Q. Lind, S.J. Wang, Y.P. Wang and S.H. Yeh

Nuclear Medicine and Cardiology (~) Services. Hospital " Reina Sofia ". CGrdoba. SPAIN

Taichung Veterans General Hospital, Talchung, Taiwan. R.O.C.

RIGHT VENTRICULAR FUNCTION IN HEART TRANSPLANT PATIENTS. We have performed 75 examinations on 29 heart transplant patients in a prospective protocol for noninvasive diagnosis and follow-up of rejection(R). The follow-up period ranged from 15 days to 44 months. The protocol comprises: First pass and equilibrium right ventriculography with 99mTe-Albumin (740 ~ q ) . Right ventricular ejection fraction of the first three cycles (EFI,EF2,EF3) after the highest point of the curve, and the mean value were obtained in the first pass study (REFX). Right ventrieular ejection fraction (RVEF) was obtained from equilibrium study using phase and amplitude images as help for R0I drawing. Endomyocardial biopsy was performed 48 hours later in all cases and pathology results were classified using Stanford criteria for rejection. Results were evaluated by comparison of tbe mean values of each and correlation analysis in relation to parameter the presence (R)-'or absence of rejection (NR); and treatable (TR) (Moderate and Severe) or nontreatable rejection (NT) (Mild and Absent). Results obtained are the following: NR R NT TR EF1 38.3+7.4 * * 32.9+7.3 36.6+7.7 * 31.3+6.6 EF2 41.1+7.6 * * 35.3+7.9 39.6+7.9 ~ 32.3+7.7 EF3 40.4+7.0 * 36.6+7.3 39.5+7.1 * 34.1+7.3 8EFX 39.9+6.5 * * 35.0+6.9 38.6+6.8 * * 32.5+6.7 RVEF 35.7+7.6 * 32.3+6.5 35.0+7.3 * * * 29.2+4.3

~p0.05,~*p0.Ol,*~p0.001 Significant correlation with biopsy existed for all parameters. In conclusion, these results provide a noninvasive diagnosis of rejection episodes an allow an accurate selection of patients with treatable and nontreatable rejection.

A ~

~

'r',_~2o:]. I~3~U'BC~I'Z(1%T ~

EVALUATE THE RESULTS OF HIGH DOSE •-GLOBULIN TREATHENT IN KAWASAKI DISEASE. Nyocardia] imaging with Tc-99m HNPAO labeled WBC (Te-WBC) was used to detect myocarditis and evaluate the results of high dose 7-glebulin treatment in Kawasaki disease. All 18 cases of [awasaki disease (1] boys, 7 glrls, mean age: 18 months) in acute stage accepted the first Tc-WBC scan before treatment. The symptoms and signs subsided

after 400mg/kg/day x 5 days 7-globulin treatment. Then the second Tc-WBC scan was arranged to evaluate the effects of the treatment for myocarditis. The Tc-WBC were prepared by a modified method (Uno K. et al. J Nucl Ned 1987;28:648), 18ml whole blood with 2ml ACD-~ solution as anticoagulant and lOmCi Tc-ggm HHPAOwere used

for each scaning. The labeling efficiency was 50+15%. The 24-hr myocardial imaging was preformed in anterior, LAO, and left lateral views. The gradings were as the following c r i t e r i a : score 0 < bone uptake; I = bone uptake; 2 > bone uptake; 3 ~ liver uptake; and 4 --~ splenic uptake. The r e s u l t s showed the severity of myocarditis had eignifcant difference between before and after a high dose -globulin treatment (P < 0.001, by signed rank t e s t ) . 39% (7/18) of total patients had significant improvement in severity of myecarditis. 50% (9/18) had not definite change. However, 11% (2/18) became more severe after a high dose ~ -globulin treatment. In conclusion, Tc-WBC scan may provide evdlences of myocarditis in tawasaki disease, even if the clincal symptoms and signs have improved after a high dose -globul in treatment.

PO-4L1-25

PO-4L1-24 N. I~tt~_r, M.J. l
Tc-gOm HI~PAO LABELED WBC SCAN TO DETECT NYOCARDITIS AND

A. C ~ i e . Alfl~

Hospit~,

ZMI)BDVES ~ O N

P~inj~ion (P~'N) of Ti-201 tl~ ~ r e p o r t ~ to incTe~ det~ion of reve&~sibilitzz of n r y c ~ a i l~ion defaults seen ~ i r ~ s t ~ stress ~Lnd l~adistri~tion (RED'N) p ~ t ~ i s . Some publis~l~ P~'N stm/die~ have l ~ higher t o t ~ d ~ of TI-201 t/nan the 2.5 n~2i (92 ~ we Y~ve ~ l y ~ for s ~ ' N oraly. We ~ whet/le~r sJ/nilar REINJ'N l~ts c~m/id l~ c ~ i r ~ wit_h~t e ~ tot~l Ti-201 dose, in l ~ t i e ~ undergoir~ planar TI-201 scintiq[ralmhy ~he stq~dy [mD~mtlati~ ~ r ~ i s t e d of I00 ~ t i e ~ in ~¢nc~n a definit~ p e ~ i ~ def~"t ~ ide/ntified on st~ J/nages (~otaJ/~ a f ~ a(~tLinistration of 71 + I0 F~q (depe/qdent ~ patient weight) of TI-201. PJ~D'N i m g e ~ of ~he ~ abr~l~ view we_re (~bt~in~d ~t_h i~at~ly befoz~ ~ 5 raJ_nut~ afffce~ ~LE]]qJ'N of 21 + 2 ~ of TI-201. ~lle i r / t i ~ stre~s i m g e ~r~ 300,000 c~unts, ~ sub~e_nt J_mag~ we-re for the s ~ time. ~he s ~ , I~'N ~ REINJ'N images were the/q d~lay~ t~et_he~ in u n p ~ ~md Metz f i l t e r ~ digit~ format ~ irf~t~d by a b l i n d ~ ~ e ~ :

DF~ P~I~E S~IRF~S -> I ~ ' N

I~IBI~ NO ( ~ G ~ MOPJB O~7I(~JS 71 26 3 I ~ ' N -> IRE]~klT'N 38* 58 4 S ~ -> RE]~J'N 81 15 4 * Of 38 d e f ~ with i r ~ zL~ve~J]0ility a f ~ RE]]qJ'N, i0 ~ d l ~ t o t ~ l y f ~ x ~ at I ~ ' N . ~=e l~e~m~it~s with a I ~ d ~ TI-201 P~E]]qJ'N r ~ i m e n (tot~ 92 + i0 Mike) &re ~ l e to t h ~ repoz~ with higher d ~ of TI-201. ~ the be~fit~s of &~l-201 I ~ ' N my ~ ~3tai~ wit-h(~/t significantly ir~i~ radi~clide ~x~t~ ~ ~-a~ation e ~ e .

K.Kletter, T.Leitha, K.Krivanek, R.Koppensteiner, A.StOmpflen, H.Ehringer, R.Dudczak. Dept.lnternal Medicine I; Div.NucI.Med.; University of Vienna, Austria.

TCg9M LABELED MONOCLONAL ANTIFIBRIN ANTIBODY (AFAb) FOR THE DIAGNOSIS OF DEEP VEIN THROMBOSIS (DVT). Recently a method to rapidly label T2Gts antifibrin (AF) Feb'fragment with Tc99m has been made available (Centocor) for detection of DVT by immunoscintigraphy (ISC). We report our preliminary findings with this radiolabeled AFAb, which is part of a multicenter trial. 34 patients (pts.) suspected of having DV7, who gave informed consent were studied. 19 of those were shown to have DVT by contrastvenography (CV, n=17) or duplex sonography / plethysmography (n=2), whereas in the remaining 15 pts CV was not indicative of acute DVT. CV of the suspected leg was performed within 24 hours of ISC. Symptoms had been present for a median of 6 days (range 3-20) before ISC and all pts were treated with heparin. Pts were injected with 0.5 mg AFAb labeled with 555-740 MBq Tc99m iv. Images were obtained immediately, 90 and 240 minutes p.i.; in 5 pts with a history of DVT in the suspected leg additional imaging was done 18 hours later. Scintigrams of the pelvic region, thighs, knees and calves were obtained for a preset time (initially 1 min, therafter 4 mini. Legs were imaged horizontal and additionally the knee and calf region being elevated by 30°. Scintigrams were analyzed visually in a blinded manner, knowing only the suspected extremity. For diagnosing DVT considering the sequential scintigraphic findings is essential, by comparing the initial findings with the later ones; thus mostly DVT diagnosis was possible at 90 min p.i. with the images at 240 min pi. being more distinct; but only one patient appeared normal at 90 minutes p.i, but not at 4 hours p.i.. All but one patient with DVT were judged abnormal by ISC (sensitivity 95%), and two pts were false positive (specificity 87%). The extent of DVT was underscored in 6 pts and overestimated in one Regional sensitivities and specificities were in the calf: 88% (15/17) and 88%, in the popliteal region: 73% (11/15) and 89%, in the thigh: 70% (7/10) and 100%, end only 33% (1/3) and 100% in the pelvis, These preliminary data show that Tc99m-AFAb ISC may play a useful role for diagnosing DVq-, comparable to that with In-111 labeled monoclonal AFAb, but allowing for a shorter investigation performance and a lower radiation burden for the patient,

649

Wednesday, 4 September 1991

PO-4L1-26

PO-4L1-27

W, H. Knapp, U. Schmidt, A. Bentrup, G. Notohamiprodjo, U. Gleichmann Institute of Nuclear Medicine and Department of Cardiology, Heart Center North-Rhine Westphalia, Bad Oeynhausen, FRG.

J.Kropp*,U.Koehler**, F.F. K n a p p , J r . * * * , H.J. Biersack*, *,** D e p a r t m e n t s of Nucl. Med. and C a r d i o l o g y Univ. B o n n / F R G , * * * O R N L Labs O a k R i d g e / U S A

MYOCARDIAL SCINTIGRAPHY IN LEFT BUNDLE BRANCH BLOCK (LBBB): RESULTS WITH T1-201 AND WITH Tc-99mMIBI

(p-123-Iodophenyl)-3-R,S-methyl-pentadecanoic acid (BMIPP) TO E V A L U A T E I S C H E M I A IN P A T I E N T S W I T H C O R O N A R Y A R T E R Y D E S E A S E (CAD). W e i n v e s t i g a t e d 20 p a t i e n t s (pts) w i t h CAD cont r o l l e d by c o r o n a r y a r t e r i o g r a p h y and left ventricular cineventriculography. The pts u n d e r w e n t a s y m p t o m l i m i t e d e x e r c i s e and 5 mCi of I1 2 3 - B M I P P was i n j e c t e d at the m a x i m a l stage of e x e r - cise. S P E C T was than p e r f o r m e d w h i c h w a s repeated a f t e r 3 hours. A t h i r d S P E C T was p e r f o r m e d a f t e r r e i n j e c t i o n of 2 mCi of BMIPP. O b l i q u e slices w e r e o b t a i n e d a f t e r f i l t e r e d b a c k p r o j e c t i o n . A f t e r n o r m a l i z a t i o n the slices w e r e c o m p a r e d by a b u l l s - e y e technique. B l o o d s a m p l e s were w i t h d r a w n at 2 min., 20 min., and 3 h o u r s p.i. Lipids w e r e e x t r a c t e d from the s e r u m and a n a l y z e d by TLC. 98 % of the d o c u m e n ted i n f a r c t i o n s c o u l d be d e t e c t e d by fixed defects in all 3 SPECT's. Segments without infarctions, supplied by a s t e n o t i c artery s h o w e d in 95 % a d e c r e a s e d u p t a k e in the first SPECT. The 3 h d e l a y e d S P E C T ' s s h o w e d no d i f f e rences. 98 % of t h e s e s e g m e n t s h a d normal u p t a k e in the r e i n j e c t i o n SPECT. H e a r t to liver r a t i o was 1:0.7. D e c r e a s e of a c t i v i t y in the h e a r t w a s 14.6% as an a v e r a g e d u r i n g 3 hours. On the TLC B M I P P a c t i v i t y d e c r e a s e d to zero a f t e r 3 h o u r s and a m o r e p o l a r p r o d u c t increased w h i c h y i e l d e d a b o u t 2.9% of the i n j e c t e d a c t i v i t y a f t e r 3 hours. B M I P P seems s u i t a b l e to d e t e c t i s c h e m i c and v i a b l e m y o c a r d i u m w i t h high accurcy. A p o l a r m e t a b o l i t e c o u l d be d e t e c t e d w h i c h has to be f u r t h e r analyzed. Research supported in part t h r o u g h a g r a n t t h r o u g h the NATO (CRG 900966).

With LBBB, T1-201 scintigraphy is indeterminate for left anterior descending coronary disease (CAD). Initial septal defects with redistribution is a common finding in LBBB, whether CAD is present or not. This study was undertaken to test the hypothesis that stress and rest imaging with Tc-99m-MIBI corresponds with initial and delayed "1"1-201images in LBBB. 184 investigations were performed in 145 patients with LBBB, 92 with T1-201 and 92 with MIBI. 30 patients were investigated with both tracers. For MIBI, a 1-day-protocol (stress/rest) was used. 68 % of the total population bad a reversible T1-201 septal deficit, 9 % a constant deficit. MIBI: 23 % and 65 %. Without evidence of CAD, 75 % of patients studied with 1"1-201 had a reversiNe septal deficit in contrast to 7 % studied with MIBI. However, 87 % of patients studied with MIBI had a constant deficit.In intraindividual comparison, reversible T1-201 deficits coincided with constant MIBI deficits in 68 % of patients. All patients with LBBB and LAD stenosis had reversible septal deficits with 1"1-201 and with MIBI. Conclusion: the septal T1-201 redistribution in LBBB without CAD is typically due to stress-independent reduction of septai perfusion. Therefore, the MIBI stress/rest image pattern - in contrast to T1-201 early/delayed imaging - differs from that obtained in CAD, so that MIBI scintigraphy can be considered for screening of CAD in LBBB.

PO-4L1-28

PO-4L1-29

D. Le 6uludec, F. Lhote, P. Weimaaz~, O. Bletry. Herson, M. Faraggi, B. Jarrousse, L. Guillevin, J.L Moretti. Avicenne, Bichat and Pitie Hospitals PARIS - FRANCL

3.Lekak~s, N.S~fak~s, P.Athanassiades, Th,Athanassoulis Ch. Kall~onLz~, H.GtannioL~, P.KosLamis, S.Moulopoulos. DepL of Clin TherapeuLics and Dept of Nuclear Medicine, Alexandra University Hospital, Athens,

SPECIFICITY OF I n - l l I - A ~ M Y O S I N MYOSIN IN Ac~i~ POLYMVOSI~S.

IN-111 ANTIHYOSIN MONOCLONAL ANIIBODY SCINTIGRAPHY IN DETECTING DOXORUBICLN CARDIOTOXICITY.

FOR

MYOCARDL~:.

Ar~timyosin scintigrs~s (AS) are used for the detection of myocyte necrosis but the specificity of the antibody for myocardial myosin remains uncertain. 48 hrs after injection of 74 MBq of Inlll-Antilyosin, planar AS of the heart and of proximal muscles (arms, thighs, legs) were performed in 10 patients with acute skeletal muscular disease : 8 pelymyositis and 2 lupus erythematosus with muscular involvement, all biologically (CRK 1647 +/- 1888), electrically &nd histologically; _confirmed. Presence of muscular uptake was assessed visually and a heart to lur~ ratio.(HLR) >= 1;85 (= mean + 2 SD value in 6 normal pts) was used-to define abnormal myocardial uptake. No patients had any skeletal muscular uptake, 8 ~-d normal cardiac uptake (HLR = 1.55 +/- .15). The 2 pts with proven myocardial involvement had positiv~ myocardial scans (HLR respectively of 2.04 ar~ 2,12). AS was repeated in both pts after 3 months of treatment, showir~ normalization of scans (HLR of 1.6 and 1.81 respectively). Conclusion : I) in-ili-Antimyosin are highly ~pecific for cardiac ~ersus skeletal muscular mvosL~. 2) Antimyosin scintigrams m~y be useful for the detection of cardiac in~,o!vement in pol~lTcsit2s.

650

To evaLuaLe the importance of antimyosin imaging For early detection of doxorubicin (D) cardiotoxlcity we examined 28 paLieots (pts) receiving chemoLherapy with D. 10 were men and 18 female and mean age was 62±8,9 yrs (range 45-78 yrs). Pie were injected 2 mCi In-111 antimyosin and planar imaging was performed 48 hrs later. Radionuelide ventricuLography was performed I week LaLer for estimaLion of ejeeLion fraction (EF) and peak filling rate (PFR). 5 pLs presenLed positive antimyosin scanning; heart to lung rakio (H/L) was 1,7±0,12 (range 1,6-1,9); EF was 46±14% (18-57%) and PFR 1,6±0,6 EDV/sec (O,~-2,&). 4/5 pts wiLh positive scanning had normal EF (>50%),white Q/5 pts showed markedly abnormal PFR (< 2 EDV/sec). Mean cumulative dose of D was 407~148 mg/m ~. In 25 pts with negative antimyosin scanning H/L ratio was 1,2q±0,I0 (range 1,0-~,4, p < 0,01); EF was 59±9% (p < 0.05) and PFR 2,4±0,9 EDV/sec (p < 0.05). 2]/2] pLs presenLed normal EF and only 2/23 abnormal PFR (<2 EDV/see, p< 0,001). Mean cumulative dose of D was 218~122 mg/m 2 (p< 0.01). In 7 pts with negative iniLia[ antimyosln sLudy, imaging was repeated 2 months Later; 2/7 pts presented abnormal antLmyosin scanning with H/L ratio 1,8; EF decreased in 1 pt (56~44%) while P[R declined in both. In conclusion, In-111 anLimyosin imaging is useful for monitoring and early detection of D cardiotoxicity. MyocyLe damage can be deLected with anLimyosin in the presence of normal EF; in these pts diastolic LV function usually is disturbed.

Wednesday, 4 September 1991

PO-4L1-31

PO-4L1-30 V. R. LELE,

P. DOUGALL,

ZG Wang, XJ Liu, RL Sun, Cardiovascular Institute Beijing, China

R.D. L E L E

J A S L O K H O S P I T A L & R E S E A R C H CENTRE, BOMBAY.

ISONITRILE MYOCARDIAL SCINTIGRAPHY-INITIAL INDIAN EXPERIENCE. 99mTC-Isonitriles are being accepted as substitutes for Thallium in e v a l u a t i o n of c o r o n a r y a r t e r y disease. W e report t h e i n i t i a l Indian experience with Isonitriles in 12@ patients with known or suspected Isohemio heart disease(50 with 99mTc-TBI & 7@ with 99mTc-HIBI). S@ S P E C T & 90 P l a n a r s t r e s s ~tudies were performed using GE-STARCAM camera. A n g i o g r a p h i c c o r r e l a t i o n was a v a i l a b l e in 2@ subjects. Overall sensitivity (Sen) & specificity (Spa) for diseased artery d e t e c t i o n was 8@% & 98% r e s p e c t i v e l y . For i n d i v i d u a l arteries: LAD CIRC RCA sen i~% 55% 80% spa 88% 90% 1@O%

ZXHe, RF Shi & Fu Wai Hospital,

CAMS,

EVALUATION AND LOCALIZATION OF THE ABNORMAL ONSET OF VENTRICULThR ACTIVATION BY PILASE ANALYSIS The onset and pattern of ventricular excitationcontraction sequence can be detected by phase analysis of radionuclide ventriculography(RNV). The location of orthodromic accessory A-V pathways(APs) in I0 patients with manifesting W-P-W ~'~drome was studied by RNV and electrophysiological techniques. 8 of 9 patients with APs were identified by phase analysis of RNV and confirmed by epicardiac mapping. In 5 patients with permanent ventricular pacemaker implantation, the sites of ventricular excitationcontraction onset were determined by phase analysis and confirmed by electrophysiology and X-ray films. Conclusions : RNV provides an accurate noninvasive techniques for detecting the location of APs and the abnormal onset of ventricular activation, especially in localizing the LV free wall AP.

A different d a y s t r e s s & rest study protocol was used. We found 99mTo-TBI images t o be inferior to 9 9 m T c - M I B I ,images d u e to excess hepatic uptake obscuring inferior w a l l in t h e former,We c o n c l u d e that i s o n i t r i l e s e s p e c i a l l y in i s e h e m i e H I B I p r o v i d e v a l u a b l e information h e a r t disease, and h a v e p o t e n t i a l in d e v e l o p i n g c o u n t r i e s like India where Thmllium is n o t e a s i l y available.

PO-4L1-33

PO-4L1-32 Ping Lu, XJ Liu, KC Li, YQ Liu Cardiovascular Beijing, China

Institute&Fu

Wai

Hospital,

CAMS,

A COMPARATIVE STUDY BETWEEN RADIONUCLIDE IMAGING AND MAGNETIC RESONANCE IMAGING IN PATIENTS WITH MYOCARDIAL INFARCTION Comparative studies between radionuclide imaging and magnetic resonance imaging(MRI) in patients with myocardial infarction(MI) were performed. The left ventricular ejection fraction(LVEF) measured by radionuclide ventriculography(TOSHIBA 90B) and MRI(FONAR) was 44.4~12.7% and 51.7±10.5% respectively in 22 patients with MI. There was a good correlation in LVEF between RNV and MRI(r=O.75,P<0.O01). Regional wall motion abnormalities of left ventricle(LV) detected by RNV and MRI was 69 and 52 respectively in total 154 segments of LV. It seemed that RNV is more sensitive for detection of regional LV function. Meanwhile we compared the results of both Tc-99m labelled MIBI myocardial tomography with TOSHIBA 90B SPECT and MRI in 19 of 22 patients. All 19 patients with MI were detected as abnormal by myocardial perfnsion imaging, but MRI detected MI in 17 out of 19 patients. The sensitivity of MRI in detection of MI was lower than that of Tc-99m-MIBI myocardial perfusion tomography. Conclusion:the sensitivity of radionuclide techniques for detection of wall motion abnormalities of LV and myocardial perfusion defects in patients with MI was better than MRI.

W.J. MacIntyre, S.A. Cook, H.T. Go, T.H. Marwick, G.B. Saha, D.R. Neumann, M.A. Antar and D.A. Underwood. Department of Nuclear Medicine, Cleveland Clinic Foundation, Cleveland, OH 44106, U.S.A. COMBINED RUBIDIUM-82 AND F-18-FDG PET IMAGING IDENTIFYING VIABLE MYOCARDIUM FOLLOWING INFARCTION

IN

The determination of viable myocardial tissue in patients following myocardial infarction is important in patient management, especially in patients considered for revascularization. Recent studies have shown that a fixed defect noted on a conventional potassium analogue myocardial perfusion image is a reliable indicator of myocardial tissue nonviability. The purpose of this study is to determine if an additional FDG study can be helpful in determining viability. To identify such viability, 33 patients with previous myocardial infarction and who had demonstrated persistent defects with stress and rest Rb-82 PET imaging were further imaged at rest with F-18 Fluorodeoxyglucose (FDG) 45 minutes after completion of glucose loading. All studies were performed on a Posicam PET system (Positron Corp., Houston, TX) either immediately following the Rb-82 procedure or within the next 48 hours. Fluoroscopic marking on the patient of heart position for the Rb-82 procedure was utilized for heart localization in the FDG procedure to obviate the need for a second attenuation measurement Of the 33 patients with Rb-82 persistent defects, nine showed FDG uptake in those areas demonstrating viable tissue. Eight of these 33 patients also had reversible defects on the Rb-82 images and all of these ischemic regions demonstrated positive FDG uptake. These results show that 27% of the patients with previous myocardial infarction that showed fixed defects on the perfusion image would have areas of myocardium falsely classified as non-viable, if FDG studies had not been added to the Rb-82 procedures.

651

Wednesday, 4 September 1991

PO-4L1-34

PO-4L1-35

F.MANNTING, R.G.14ORGAN,E.RARIPUU & A.ISKAELSSON University Hospital, Uppsala, Sweden.

P.Y. MARIE, G. KARCHER, P. OI-IVIER, N. DANCHIN, C. MEZERAY, Y. JUILLIERE, F, CHERRIER, A. BERTRAND Service de M~decine Nucl6aire et de Cardiologie, CHU Nancy, France USEFULNESS OF REST REINJECTION AFTER EXERCISEREDISTRIBUTION SPECT T1201 FOR THE DETECTION OF REVERSIBLE STRESS ISCHEMIA AFTERMYOCARDIALINFARCTION

GATED vs NON-GATED SPECT FOR QUANTITATIVE ASSESSMENT OF MYOCARDIAL PERFUSION WITH 99m-Tc SestaMIBI (CARDIOL1TE) The aim of this study was to analyze the cost/benefit of gated SPECTfor quantified assessment of myocardial perfusion abnormalities using 99m-Tc (Cardiolite)(C). We studied 12 normals (Nl) and 24 pts with CAD according a the one-day C protocol: 250 MBq at rest with imaging after lh, followed by 900 MBq at peak stress and imaging after lb. The studies were acquired using gated SPECT, 8 frames/cycle, 32 angles, 32 s/angle, and processed to: A) a l l frames summarized (=non-gated study) and D) a study consisting of only diastolic frames defined as the frames with constant LV volume. Camera time was 50% longer and filtering/reconstruction time 8 times longer than for a std SPECTstudy. Each study required 8 times more space. High quality dynamic sagittal and coronal studies, demonstrating perfusion & wall motion in a l l parts of LV were obtained. RV appeared more pronounced in D studies than in A studies (p<.Ol). The LV cavity was larger in D than in A studies (p<.O01), leading to more coronal slices with cavity (p<.O01). An inverse relation between LV dimension and increase in number of coronal slices with cavity in D studies were seen ( r : -.87 p<.O01). Perfusion defect size were not different (p> .05), but in 3 pts with proven non-Q infarcts perfusion abnormalities were only detected in D studies. We conclude that cost in time and space of gatedSPECT is offset by the perfusion/wall motion information, and better definition of the LV wall and cavity. Gated SPECT seems particularly useful in pts with small hearts or LV hypertrophy, and may lead to detection of smaller perfusion abnormalities.

Rest reinjection, performed after exercise-redistribution SPECT TI201, might improve the detection of ischemic but viable myecardium. The aim of this prospective study was to evaluate the interest of rest reinjection for ~.i~e detection of reversible stress ischemia (RSI) after myocardial infarction. Exercise SPECT TI201 was carried out in 53 pts (56 + 10 years), a mean of 31 + 14 days after myocardial infarction. Tomoscintigraphic acquisitions were performed (1) after exercise, (2) 3-4 hours later (redistribution : RD) and (3) after reinjection of 1 mCi of TI 201 (rest reinjection : RR). Results were analysed by 2 trained observers using a 20-segment division of the left ventricle. RSI was defined as the existence of partial or complete reversibility on at least one segment with a stress defect and was observed in 4 1 % of pts after RD, 55 % after RR and 58 % after RD or RR. In 22 pts RSI was already observed after RD (group A). In 9 pts, RSI was only identified after RR (group B). The number of segments with a stress defect was similar in both group (group A : 5.8 + 2.7 vs group B : 6.0 _+2.0, NS). However, the number of segments with a reversible stress defect was lower in group B (group A : 3,3 + 2.1 vs group B : 1.4 + 0.7, p<0.02). Qonclusion : After myocardial infarction, the occurence of RSI, assessed with exercise-redistribution SPECT TI201, increases when rest reinjection is performed. However, RSI is less important when reversibility is only observed after restreinjection.

PO-4L1-36

PO-4L1-37

J. Mester. I. K6sa, N. Gruber, G. Kov~cs, L. Csernay A. Szent-GySrgyi Med. Univ. Dept. Nucl. Med., Dept. Cardiac Surgery, 2rid Med. Clinic, Szeged, Hungary.

P-Y. MIGNOLET, J. DONCKIER, F. CAUWE, H-J. SHET, C. BRICHANT, J. HELIN, C. BECKERS, P. DE COSTER. Centre de H~deeine Nucl~aire, University of Louvain Hont-Godinne, 5530 Yvoir, Belgium

201-T1 REINJECTION IN PATIENTS B E F O R E C O R O N A R Y B Y - P A S S SURGERY. IMPROVED PREDICTION O F POSTOPERATIVE PERFUSION. In 7 single vessel (LAD) coronary patients 5-12 days before coronary by-pass surgery (CBS) standard dipyridamole-2@l-Tl perfusion scintigraphy (0.56 mg/kg dipyridamole, 2 mCi 2@I-T1) w a s performed. S P E C T acquisitions w e r e made immediately and 3 hours after 2@I-T1 injection. After completion of the redistribution study, 1 mCi of 2@I-T1 w a s injected. R e p e a t e d S P E C T acquisitions were done i~ min and 1 hr following reinjection. 3 weeks after CBS, myocardial perfusion scintigraphy w a s r e p e a t e d without reinjection. Pre-operative stress perfusion defects (PDs) were found in all investigated patients. In 3 patients small, in further 3 patients relatively large persistent defects were observed. Small defects have shown minor, but large defects dramatic reduction in their size in the I@ min post-reinjection study. Further significant improvement w a s detected on the images of the 1 hr reinjection study in 2 patients. Post-operative stress scintigrams corresponded more to the results of the reinjection study, than to those of the redistribution images. 2 of the 3 patients with large persistent defect in the 3 hr redistribution study had completely normal post-operative stress scintigrams. In conclusion, in patients with permanent PDs in 2@I-TI redistribution images, reinjection study contributes to better prediction of postoperative results, PDB on the 10 min post reinjection study m a y disappear after 1 hr.

1-123 MIBG MYOCARDIAL IMAGING IN DIABETIC AUTONOMIC NEHROPATHY To determine if cardiac autonomic neuropathy (CAN)

652

induces changes of myocardial uptake or washout rate of 1-123 MIBG in diabetic patients (pts), ll pts (7 men, 4 women; mean age 53 years) were evaluated both with HIBG imaging and 5 cardiac autonomic tests (CAT) previously described by Ewing and consisting of heart rate and blood pressure responses to different maneuvers. All pts were off drugs known to interfere with MIBG and had a normal stress T1-201 scan. Planar imaging was performed 30 and 200 min after i.v. injection of 370 HBq MIBG. Definite CAN was considered if at least 2 CAT were abnormal (5 pts) and CAN was considered doubtful if only 1 CAT was abnormal (2 pts). Cardiac activity was quantified by drawing regions of interest (ROIs) around the left ventricle. Background subtraction was performed using a mediastinal ROI. The washout was evaluated by means of the decrease in activity between 30-200 min, expressed as the percentage of the 30 min activity. The initial uptake was considered as the myocardial versus mediastinal ratio at 30 min. This initial uptake was similar in pts with or without CAN. The myocardial washout of HIBG between 30 and 200 min, was significantly higher in definite CAN pts (26±8%; 18-40) compared with pts having normal CAT (8±8Z; 0-16; p<0.02). If doubtful CAN pts were included, this difference remained significant (27±9Z; 18-40; p<0.01). In conclusion, these data suggest that 1-123 HIBG scintigraphy is a reliable noninvasive method for the assessment of myocardial adrenergic system disintegrity in pts with definite and doubtful CAN.

Wednesday, 4 September 1991

PO-4L1-38

PO-4L1-39

i,~ Mole~_*.,V Di Bello, 0 Boni *, CrR. Ballina*, S Berti #, U.Conti ~, E Lazzem *, F. Matteuccl *, C. G~orgl ~, G,lervasl#.O. Marlam, R.Blar,cm~.

L. Mortelmans*, E. L e s a f f r e * * * , J. Nuyts*, M. De Roo*, J. Vanhaecke**, F. Van de Werf** * Div. Nucl. Med., * * Cardiology and * * * B i o s t a t i s t i c s , U . Z . K . U . Leuven, Belgium

2ridMedicalClinic;*Cardiovascular Medicine Division,*Center of Nuclear Mediclne, Universityof P]sa and # CNR Istituteof Chnical Physlo~og7 Pisa, Italy. DETECTION OF CORONARY ARTERY DISEASE BY EXERCISE THALLIUM-201

$CINTIL~RAPHY (TS), HIGH DOSE DIPYRIDAMOLE ECHOCARDtoGRAPNY (DET) AND EXERCISE ELECTROCARDIOGRAPHY fEET): COMPARISON AMONG THREE NONINVASIVE METHODS ,The aim of thisstudy was to evaluatesensitivity,specificity,accuracy, predictlvevalue of TS, DET and EET m the detectionof angmgraphlcaiiy assessedcoronary artery disease.The 66 patients (pie) we studied(51 men, 15 women, age range 35-67 yrs) underwent TS, DET and EET after adeguatepharmacologicalwash-out; 38 had hystoryof angina peclorisand 28 of previousmyocardia] Infarction.The three studieswere performed as follows;a) maximal bicycleEFT followingthe Bruce's protocol;b) DET, 2d-ecno-ecgmonitoringduring InfusionoI 0.56 mglkg over 4', followedby 4' of no infusion,and then,iftestwas negative,by an additional0,28 mglkg over 2'; c) 2.0 mCi of Thallium-201 (T]-201) was injectedat peak of exercise and exercisewas continuedfop an additionalminute (using the same protocol as fop EET); mltlal (5'-after Injectionof TI-201) and delayed(4 hours),imagingwere acquired( I0 rainfor each) in the 45 ° LAO, anterior and 70°LAO projection.EET was conslderedpositivewith an ST >O,ImV at 80 ms for J point. PositiveDET was consideredfor transient ~/nergy of contraction(hatwas absentor of lesserdegree in the baseline examination. 201-TS was consideredpositive in presence of reversible perfuslon eegmenlal defectsin the redistributionimaglng as comperlson with thestress.Selectivecoronaryarteriographywas performed in all pts within two weeks the above tests:a vesselwas conslderedto nave significant obstuctionin presenceof ,70% narrowing.

EET

DET

TS

Sensitivity 75 % 76 % 90 % Specificity 41% 75 % 85 % Accuracy 68 % 76 % 87 % Posibve predictivevalue 83 % 92 % 95 % Negativepredictivevalue 27 % 42 % 64 % In conc]uslonexermse Thal]ium-20I scintigrapnyseem to be better than DET and EET in detectingartery disease due to its greater sensitivity, specificityand accuracywhen compared with anglographicfindings.

PO-4L1-40 G. N A R A I N ,

LONG TERM FOLLOW-UP OF THE BENEFICIAL EFFECT OF THROMBOLYSIS ON GLOBALAND REGIONAL LEFT VENTRICULAR FUNCTION.

The aim of the study was the functional re-evaluation of 296 patients 12 to 18 months after a double-blind t r i a l evaluating the effect of rt-PA versus placebo given within five hours of onset of symptoms. All patients underwent rest-stress radionuclide angiography (RNA). For each stage the global l e f t ventricular ejection fraction (LVEF) was calculated together with an estimate of regional wall motion abnormalities (RWMA) defined by the definition of 8 sectional EF's and of one single index (Ind.) (Goris '84). Results of both groups were s t a t i s t i c a l l y compared and correlated to parameters measured at the hospital stage. A clear difference of the total workload and the peak workload was found between both groups. A significantly higher value of maximal LVEF and LVEF at the endpoint was found in the thrombolytic group. Study of RWM at rest showed only a difference in the apico-infer i o r region. Discriminant analysis using the Ind. at peak LVEF and at the endpoint revealed less wall motion abnormalities in the treated group, A multivariate regression analysis showed the prognostic value of LVEF and RWMAat the subacute stage. We conclude that radionuclide analysis was able to prove a better functional capacity and a more optimal coordination of myocardial c o n t r a c t i l i t y during stress RNA. At rest, no major differences were found between the hospital stage and the one year follow-up. Early measurement of ventricular function and perfusion by RNA and Tl scintigraphy provides prognostic information.

PO-4L1-41 D. M A ~ H U R ,

M.

CHATURVEDI,

C. M E E N A

D I V I S I O N OF N U C L E A R M E D I C I N E SMS M E D I C A L C O L L E G E H O S P I T A L J A I P U R (INDIA] 3 0 2 0 0 4 LEFT VENTRICULAR DYSFUNCTION HYPOTHYROIDISM : A RADIONUCLIDE ASSESSMENT

IN

Patients with long standing hypothyroidism have symptoms suggestive of i s c h e m i c heart disease along with nonspecific ECG c h a n g e s , which revert to normal after thyroid medication. We evaluated 45 female hypothyroid p a t i e n t s w i t h the a b o v e f i n d i n g s to f i n d out whether they had left ventricular (LV) d y s f u n c t i o n also. LV functions at rest and d u r i n g e x e r c i s e w e r e s t u d i e d by r a d i o n u c l i d e M U G A s t u d i e s on a g a m m a c a m e r a u s i n g Tc 9 9 m labelling. We f o u n d t h a t 80% of o u r p a t i e n t s h a d a resting ejection fraction b e l o w 60% c o m p a r e d to c o n t r o l s who had above 70%. 60% of our patients h a d a f a l l of L V E E of 10% or m o r e while 29% h a d a r i s e in EF. T h i s r i s e w a s less than 10% after exercise, while the c o n t r o l s h a d a 10% or m o r e rise. We infer that hypothyroidism significantly affects LV function and may be reversible. T h i s s h o u l d be c o n s i d e r e d while t r e a t i n g p a t i e n t s of h y p o t h y r o i d i s m .

Mark A. Nedelman, Harlan F. Weisman, Daniel J. Lahey, A. Bertrand Brill and Thomas F. Schaible. University of Massachusetts Medical Center, Worcester, MA and Centocor, Inc. Malvern, PA, USA. SPECIFICITY OF TECHNETIUM-99M T2GIs FAB' FOR ACUTE THROMBI: EVALUATION IN A CANINE MODEL OF VENOUS THROMBOSIS Technetium-99m (Tc-99m) labeled T2GIs Fab', a monoclonal antibody fragment directed against the betachain of human fibrin, detects acute venous thrombi with high sensitivity. The epitope is sterically blocked with progressive fibrin crosslinking and is cleaved by plasmin fibrinolysis, likely reducing antibody binding as thrombus ages. Thus, the location of the epitope may permit T2GIs to distinguish acute from older thrombi, a problem with all current diagnostic tests for deep venous thrumbosis (DVT). To test this hypothesis, femoral vein thrombi, induced by thrombogenic coils were allowed to age i, 3 and 7-9 days before iv administration of 0.5 mg/10-15 mCi of Te-99m T2GIs Fab'. Antibody uptake was unequivocally apparent in 4 hour images of 1 day (n=3) and 3 day (n=3) old thrombi but not in 7-9 day (n=2) old thrembi. Quantitative analysis of images was conducted by setting regions of interest over the thrombus and background (muscle in contralateral leg). One day and 3 day old thrombi had target-to-background ratios of 2.14 + 0.27 and 1.79 ~ 0.08, respectively (p=NS). Seven to 9 day old thrombi ratio was 1.36 + 0.I0 (p< 0.05 vs i day old thrombi). Thus, Tc-99m T2GIs Fab' is a specific marker for acute venous thrombosis, a property which could provide unique capabilities in the diagnosis of DVT.

653

Wednesday, 4 September 1991

PO-4L1-42

PO-4L1-43

G . Porenta, J. Czernin, R. C. Brunken, S. Y. Cban, R. A. Hawkins, M. E. Phelps, H. R. Schelbert, UCLA School of Medicine, Los Angeles, CA.

Elizabeth Prvulovich, G. M. Shah, S.R. Underwood ,D.E.Jewltt, King's College Hospital and *Royal Brompton and National Heart Hospital, London, U K.

A COMPARISON OF VISUAL ANALYSIS WITH CIRCUMFERENTIAL PROFILES TO ASSESS PET ISCHEMIA: A ROC STUDY

THE PHASE HISTOGRAM INFARCTION ?

To delineate the variability of visual analysis in assessing PET ischemia defined as maintained glucose metabolism in hypoperfused m¢ocardium, we studied myocardial blood flow and glucose metabolism with 13-N ammonia and 18-F deoxyglucose in 20 patients with angiographically documented CAD. Four experienced observers independently graded 8 myocardial segments twice on a 5 point grading scale. Intraobserver variability was defined as the pement of scores that differed by more than one grade point between the two scoring 0 • j rounds and was 14_+1%, 14-+3%, 0 FP 1 and 9_+5% for scores of presence, extent and severity of ischemia. Receiver operating curves (ROC) relating the true positive (TP) to the false positive (FP) fraction were derived by comparing observer scores to circumferential profile analysis, We conclude that visual analysis of PET ischemia is associated with an acceptable intraobserver variability and yields reproducible ROC curves between observers consistent with a low interobserver variability.

Prognosis following myocardial infarction is related to extent of infarction and left ventricular ejection fraction. Their relationship with the extent of regional wall motion abnormality is unknown. We have therefore studied 40 patients (mean age 55 years, 30M, 10F) six weeks after their first transmural myocardial infarction (20 anterior, 20 inferior), using exercise thallium emission tomography and exercise equilibrium radionuclide ventriculography. The thallium tomograms were assessed semiquantitativety to produce indices of fixed and reversible ischaemia which combined both extent and severity of defect. Regional wall motion was assessed from the standard deviation (SD) of the phase histogram. Mean LVEF was 49%, range 21 to 76% (anterior) and 61%, range 43% to 76% (inferior). There were significant correlations between LVEF and size of infarct (r =-0.68, p <0.001), SD of LAO phase and LVEF (r=-0.70, p<0.001) and SD of LAO phase and size of infarct (r=0.55, p<0.001), The correlation between SD of phase and size of infarct was better in patients with anterior infarction (r=0.55, p=0.018) than inferior infarction (r=0.35, p=0.08) which may be explained by attenuation of the inferior portion of the blood pool, We conclude that in anterior infarction SD of LAO phase is related to the extent of infarction and to LVEF and may prove valuable as an objective and easily measured parameter when assessing prognosis following acute myocardial infarction.

PO-4L1-44

PO-4L1-45

Elizabeth Prvulovich, G M Shah, S R Underwood*, D E 3ewitt. King's College Hospital and *Royal Brompton & National Heart Hospital, London, U.K.

W. Richter, R. Schroeder, G. Eichstaedt, R. Felix Dpts. Radiology and Cardiology, Hospital R. Virchow, Berlin, FRG

1S

LEFT POSTERIOR OBLIQUE RADIONUCLIDE VENTRICULOGRAPHY IN THE ASSESSMENT OF WALL MOTION ABMORMALITY Equilibrium radionuclide ventriculography is used in the assessment of left ventricular ejection fraction (LVEF) and wall motion abnormalities in patients with coronary artery disease, imaging is usually confined to the left anterior oblique (LAO) projection but this has been shown to be less sensitive for abnormalities of the inferior wall. We therefore assessed the value of the left posterior oblique (LPO) projection which should be superior for abnormalities of the inferior wall. Twenty patients with recent transmural anterior infarction and 20 with tramsmural inferior infarction were studied by LAO and LPO radionuclide ventriculography. The findings were compared with the findings in 15 subjects without cardiac disease. Mean (-+SD) LVEF in patients with anterior infarction was significantly lower than normal (56%_+15.6% versus 71%_+7.1%, p=0.028), but in the patients with inferior infarction was not (65%_+12.8%). LAO phase and amplitude abnormalities were seen in 15 (75%) and 20 (100%) of the patients with anterior infarction, but in only 7 (35%) and 10 (50%) of the patients with inferior infarction. By comparison, LPO phase and amplitude abnormalities were seen in t 6 (80%) and 17 (85%) of thte inferior group. The standard deviation of the LAO phase histogram was similarly less sensitive for the detection of inferior infarction than anterior infarction (normal 9.9°-+1.5°, anterior infarction 18.8=+7.8 =, inferior infarction 12.6°-+4.6°). Sensitivity of the LPO phase histogram was maintained (normal 11.8°+3.3 °, inferior infarction 16.3°-+4.4°, p=0.033). We conclude that LPO equilibrium radionuclide ventriculogrsphy should always be performed in addition to LAO imaging in order to obtain a full picture of regional ventricular wall motion.

654

- A REFLECTION

OF EXTENT OF

Barzen,

4.

University

TL-REINJECTION OR LATE SCINTIGRAPEY DETECTION OF LATE REDISTRIBUTION MYOCARDIAL SPECT?

FOR IN

Late redistribution phenomena in 201-TI myocardial SPECT can be demonstrated either by late scintigraphy after 24 hours or by reinjection of approximately 1 mCi 201-TI. The aim of our study was to compare these two techniques with regard to their diagnostic usefulness. We performed late seintigraphy after 24 hours in 33 pts. with evidence of incomplete redistribution in the resting scan. While in 15/33 pts. late scintigraphy was performed before and after reinjection (group I), in all other pts. scans were obtained after reinjection only (group II). 19/33 of all pts. had evidence of late redistribution. In 4/16 group I pts. reinjection contributed to diagnosis whereas segmental analysis revealed no significant difference between scans performed before and after reinjection in the remaining 1.2/16 pts. Conclusion: Reinjection can be avoided in many cases if scans without reinjection were performed after 24 hours. Late scintigraphy without reinjection is often sufficient for diagnosis.

Wednesday,

4 September

1991

PO-4L1-46

PO-4L1-47

N. R i l i n g e r 1, G.H, R e i l 1, D.L. Munz2, H. Niemann 1

F. ScopinarO, M. Banci, M. Pagan, O. Schillaci, C. Greco*, A. Centi Colella Section of Nuclear Medicine, Dpt.of Experimental Medicine,*Ist. of Card. Surgery, University "La Sapienza", Rome, Italy

1) St~dtische K l i n i k e n Oldenburg, Dr. Eden-Str. 10, W-29 Oldenburg 2) U n i v e r s i t ~ t G6ttingen, Nuklearmedizin, W-34-G6ttingen EVALUATION OF MYOCARDIAL VIABILITY AND CLINICAL RELEVANCE OF THALLIUM 201 REINJECTION IN THE MANAGEMENT OF CORONARY ARTERY DISEASE. I t was t h e aim o f t h i s study t o e l u c i d a t e the d i a g n o s t i c value and the c l i n i c a l relevance o f the Thallium 201 (T1 201) r e i n j e e t i o m method (RI) in t h e management o f coronary a r t e r y disease (CA) in p a t i e n t s (pts) w i t h p e r s i s t e n t T l - d e f e c t or q u e s t i o n a b l e r e d i s t r i b u t i o n a f t e r stress and r o u t i n e l y 3 h delayed SPECT (DL) s t u d i e s , Method: A t o t a l o f 60 SPECT s t u d i e s was performed in 20 pts w i t h known CA, 12 pts w i t h old myocardial i n f a r c t i o n 8 pts w i t h angina p e c t o r i s and p a t h o l o g i c a l angiogram, At t h e peak o f exercise 74 HBq T1 201 were i n j e c t e d . Post stress as w e l l as 3 h delayed SPECT studies were r o u t i n e l y performed. In a d d i t i o n 1-4 days l a t e r 48-74 MBq T1 201 were i n j e c t e d at r e s t and RI SPECT was begun 1020 min l a t e r . - S t r e s s and r e s t s t u d i e s were i n t e r p r e t e d v i s u a l l y as w e l l as q u a n t i t a t i v e l y using Bullseye t e c h nique. Furthermore'~o compare s t r e s s and RI studies each coronal image was d i v i d e d i n t o 8 segments t o diagnose ischemia or scar. Results: O u t , o f 96 defects in T1 201 s t r e s s study 67 show p e r s i s t e n t d e f e c t in DL and 48 i n RI. 27 segments (28%) show r e d i s t r i b u t i o n in DL whereas 48 segments(50%) show new T l - f i l l i n using RI. In 6 pts T1 RI was the dec i s i v e approach f o r t h e r a p e u t i c a l d e c i s i o n . We conclude t h a t T1 201 r e i n j e c t i o n i s an important method f o r c o r r e c t e v a l u a t i o n o f myocardial v i a b i l i t y and f o r optimal c l i n i c a l treatment planning.

DETECTION OF REST HYPOPERFUSED MYOCARDIUM BY 99mTc-MIBI SCAN. USEFULNESS IN CARDIAC SURGERY Detection of viable but rest hypoperfused myocardium is an important aid in clinical decision making in cardiosurgery. 99mTc-MIBI uptake is correlated to regional myocardial blood flow. Nitrate-induced vasodilatation may increase the regional blood flow and the 99mTc-MIBI uptake. 20 pts. were studied with 99mTc-MIBI injected A) At rest and B) During vasodilatation caused by nitrates. The scans were performed in 3 standard views by a computer-assisted gamma camera. Each view was divided in 5 sectors (s.)(15 s. per study), i0 pts. underwent coronary by pass or percutaneous angioplasty (P.T.C.A.). A third study with rest injected ~gmTc-MIBI was performed in these pts., i to 3 months after the treatment. The study A) showed lack of myocardial uptake in 102 out of 300 myocardial s. (80% of agreement with coronarography). 33 out of these showed restored uptake at the B) scan. In the i0 pts. who underwent by pass or P.T.C.A., the A) scan showed lack of uptake in 47 s., the B) scan shewed restored uptake in 16 s. and the scan performed after treatment showed a moderate to normal 99mTc-MIBI uptake in 22 out of the 47 s. All the s. but 2, with restored uptake at the B) scan, showed restored uptake at the scan performed after treatment. At the moment, the collected data suggest that: l)lack of 99mTcMIBI uptake at rest does not always indicate scar; 2) the scans detect at least part of the viable but rest hypoperfused myocardium.

PO-4L1-48

PO-4L1-49

V, Podio*, M.T. Spinnler °, T. SDandonari*. C. Moretti °, M Bessone*, G. Castellano*, G,L. Turco*

Steinmetz h. ShemeshJ+,FismanEZ+,Kellerman JJ+ + Department of Nudeax Medidne, CardiaoRehabilitation Institute Sheba Medioal Center, TeI-Hashomer, Sadder Faculty of Medidne TeFAvivUniversity,Israel

*Cattedra di Medicina Nucleate - L)niversit& di Totino (Italy) °lstituto di Medicina e Chirurgia Cardiovascolare - Universit& di Tonno (Italy)

MIBG as an Index of Cardiac Innervation in Human Myocardial Infarction To assess regional myocardial sympathetic innervation after acute myocardial infarction (MI), we evaluated the distribution of nerve endings using meta[1231]iodobenzylguanidine (MIBG). Moreover, we compared MIBG scans with perfusion images with ZOlTI (TI), Ten untreated patientts, five to ten days after first episode of MI were studied by MIBG and stress TI scintigraphy. All the patients underwent a coronary angiography, a contrast ventriculography and serial echocardiograms. Four months and one year after MI, scintigraphic studies with MIBG and TJ w e r e repeated. Myocardial MIBG images were acquired 15 rain, 90 rain, 4 hours and 24 hours after injection in the same standard views of TI images (Anterior, LAO 45 ° and LAO 70°). Quantitative analysis of MIBG scans were compared with correspondent redistribution TI images. In each set of images we compared MIBG washout rate both in the region of MI and in the region apical to MI. We analyzed qualitatively and quantitatively the MIBG scans obtained at different times after MI. In our patients, comparison between stress and redistribution TI scans did not show ischemic regions. Cardiac perfusion, as shown by TI images, and ventricular function (echocardiography) did not change significantly during our investigation. Qualitative and quantitative analysis showed that MIBG uptake defect were more extensive than perfusion defects. Circumferential analysis at one week, four months and one year did not show any significant change in MIBG uptake, both in necrotic areas and in regions apical to MI. Our study shows that: 1. regional sympathetic denervation can be established non invasively with scintigraphic technique; 2. area of sympathetic denervation includes necrotic region and region apical to MI; 3. in our patients population, there is no evidence of reinnervation of area distal to infarction one year after MI.

THE HEMODYNAMICEFFECTSOF NISOLDIRNE ON SILENT MYOCARDIALISCHEMIA The purpose of this studywas to assess the influence of Nisoldipine ~P) on patients with silent myocardial ischemia, We evaluated the hemodynamio effects of shoK~termoral administration of NP by means of radionudide Ventriculography(RR~, Nineteen male patients (mean age 62 +h G years) with documented corona`,y after, disease, but without angina pectods or impaired left ventricular function were selected, Ina randomized double blind study 10 mg of NP was given each morningfor two weelu and placebo in the next fofmight or vice versa, Re~ng and stress RNV-~ were performed at the beginning of the study as baseline° after the first two weeks and after the seoondtwo weeks, For each RNV left ventdcular ejection fraction El:), end diastolic volume (EDV), end systelin volume (Eb"V), cardiac output (CO), peak ejection rate (PER), peak filling rate (PFR) and estimated systemic vascular resistance (Eb"VR)were calculated, In the resting studies mean heart rate rose from &8 to 73 on NP treatment (.o':0,05), ESV tended to decrease with NP, but was not statistie.ally si9nifioant, However EF increased from 62% to 66% (p
655

Wednesday, 4 September 1991

PO-4L1-50

PO-4L1-51

Eaillefer R., Freeman M., Greenberg D., Picard M., Chen F., Lamoureux F., Humen D., Rosenthall L., Klolber R., Frlede J., Fung A., Dalgneautt L., Lalonde L., Eng FHT *

N. Takahashi. N. Tamaki, H. Ohtani, M. Shindo, Y. Yonekura, R. Nohara, H. Kambara, C. Kawai, J. Konishi, *T. Toyama, *Y. Ishii, *K. Torizuka. Kyoto University Faculty of Medicine, Kyoto, and *Fukui Medical School, Fukui, Japan.

COMPARISON BETWEEN g~Tc-TEBOROXIME AND 2°1THALLIUM PLANAR MYOCARDIAL IMAGING IN THE DETECTION OF CORONARY ARTERY DISEASE IN A CANADIAN MULTICENTRE TRIAL. In a study involving 10 Canadian centres, the efficacy and sensitivity of 99mTc-Teboroxime (TEBO) in the detection of coronary artery disease (CAD) by planar myocardial perfusion imaging were evaluated and compared to 201-TI (TL) in patients with significant disease on coronary angiography (>50% stenosis) done within 3 months of the TEBO study. Fifty-four patients (10F, 44M, mean age: 56) were submitted to two treadmill stress tests within 3 weeks. The level of stress was similar for the 2 tests (double product was 22,800 for TL and 22,200 for TEBO). Planar imaging (3 views) was performed at 5 min and 4 hrs after injection of TL (2.2 mCi) and at 2 min after injection of TEBO (15-25 mCi, 1 min/view for the first two views and 90 sec for the last view) at stress. Two hours later, a second injection of TEBO (18-25 mCi) was given for the study at rest. Blinded reading was performed by 4 observers. The left ventricle was divided into 3 segments in each view. Twenty patients had single vessel disease, 14 had double, and 13 had triple vessel disease (7 patients had normal angiograms). TL and TEBO detected 113 and 104 ischemic segments and 49 and 39 fixed defects respectively. The sensitivity for CAD detection was 85% for TL (40 T.P, 7 F.N.) and 83% for TEBO (39 T.P., 8 F.N.). Coronary angiogram showed 87 stenosed arteries (35 LAD, 25 RCA, and 23 CX). TL detected 42 vascular territories and 40 were detected by TEBO. In conclusion, TEBO and TL planar imaging are similarly sensitive in the detection of CAD. TEBO imaging was rapidly completed. • HoteI-Dieu de Montreal, St, Michael's Hospital (Toronto), Health Sciences Center (Winnipeg), Hopital St. Luc (Montreal), Montreal General Hospital, Hopital Notre-Dame (Montreal), Health Sciences Center (Edmonton), Foothills Hospital (Calgary), HoteI-Dieu de Quebec, Vancouver General Hospital, Squibb Diagnostics Canada (Montreal).

DISCORDANCE OF STRESS TC-99m METHOXYISOBUTYL ISONITRILE AND THALLIUM IMAGING. Experimental studies suggest different mechanisms of Tc99m methoxyisobutyl isonitrile (MIBI) uptake from TI. To evaluate the discrepancy of MIBI and TI in the clinical study, stress perfusion SPECT using MIBI and TI was obtained in 11 normal subjects and 36 patients with coronary artery disease, including 16 with myocardial infarction and 16 with post PTCA or CABG. The distribution in 5 myocardial segments was assessed blindly with a 5 point grading system (1=normal, 5=defect). The discrepancy between the images was considered present when the difference in score was >2. The discrepancy was observed in 12 of the total 235 segments (5%) from 9 patients (19%). postmoderate distribution n revasculadzed stenosis soasm unknown MIBITI 9 4 4 1 0 total 12 5 4 1 2 Relatively increased uptake of MIBI as compared to TI was often seen in the post-revascularized segments and ischemic segments with moderate (75-90%) stenosis. We conclude that the discrepancy between MIBI and TI distributions was occasionally but not quite often observed in stress perfusion imaging. The major causes of such discrepancy may be postischemic myocardium and mild ischemia.

PO-4L1.52

PO-4L1.53

N. Takahashi. N. Tamaki, H. Ohtani, M. Shindo, Y. Yonekura, R. Nohara, H. Kambara, C. Kawai, J. Konishi, T. *Toyama, *Y. Ishii, *K. Torizuka. Kyoto University Faculty of Medicine, Kyoto and *Fukui Medical School, Fukui, Japan.

Y. Taniguchi, T. Shudoh, K. Miyao, M. Shima, M. Iwanami, M. Takakura, H. Tsuji, M. Kitamura, H. Kotera*, M. Murata* Kyoto Second Red Cross Hospital, Internal Medicine and *Radiology 355-5 Haruobi-eho Kamanza-dori J-602 Kyoto Japan

INTEROBSERVER VARIANCE OF TC-99m METHOXY ISOBUTYL ISONITRILE MYOCARDIAL IMAGING.

QUANTITATIVE ANALYSIS OF RIGHT VENTRICULAR PERFUSION ON 201-THALLIUM SPECT IN RIGHT VENTRICULAR PRESSURE OVERLOADING CONDITION --- COMPARISON WITH RIGHT VENTRICULAR PRESSURE, AND WALL THICKNESS ON MAGNETIC RESONANCE IMAGING

Tc-99m methoxy isobutyl isonitrile (MIBI) provides high quality myocardial perfusion images due to higher photon flux. This study was undertaken to determine whether MIBI images may yield less interobserver variance in interpretations than TI. Stress and delayed myocardial perfusion SPECT imaging using both MIBI and TI was performed in 43 patients. Four physicians scored the distribution in 5 myocardial segments of each scan as 5 point grading system (1=definitely normal; 2=probably normal; 3=equivocal; 4=probably hypoperfused; 5= definitely hypoperfused) to classify as completely agreed (max. difference=0), partially agreed (=1) and discrepant (_>2). anterior seotal aoex inferior lateral to~al Completely MIBI 21 28 24 32 46 151 aoreed TI 20 18 29 26 53 146 Partially MIBI 51 46 48 45 35 225 ~greed TI 51 ,50 46 41 27 215 Discrepant MIBI 14 12 14 9 5 54 TI 15 lg 11 1~* 6 69 (*p<0.05) MIBI scan provided slightly less interobserver variance on interpretation in inferior regions than TI, probably due to more uniform distribution with less photon attenuation on MIBI images. In conclusion, the high quality SPECT perfusion imaging using MIBI may yield more confidence in interpretations with less interobserver variance.

656

The purpose of this study is to clarify usefulness of quantitative analysis of right ventricular perfusion on 201-Thallium (TI) SPECT in right ventricular overloading condition, in comparison with right ventricular pressure in cardiac catheterization and wall thickness on magnetic resonance imaging (MRI). Seventy-four MBq of TI was intravenously injected to 25 subjects with right ventricular overloading (pulmonary hypertension, pulmonic valvular stenosis, pulmonary embolism, ASD). Regions of interest (ROI), 2 × 2 pixel, were selected on right and left ventricular free walls in mid-ventricular short axis images of SPECT. The right ventricle/left ventricle (RV/LV) uptake ratio of TI was calculated. Right ventricular wall thickness of the region corresponded to the ROI on SPECT was measured on MRI. Right and left ventricutar pressure was recorded in cardiac catheterization, and systolic pressure ratio (RV/LV) was calculated. There was significant positive correlation (r=0.79, p<0.02) between the uptake ratio and the right ventricular wall thickness. The uptake ratio was positively correlated with systolic right ventricular pressure (r=0.59, p<0.046) and the pressure ratio (r=0.60, p<0.046). We concluded that the quantitative analysis of right ventricular perfusion on SPECT was useful to estimate right ventricular pressure and wall thickness in right ventricular overloading condition.

Wednesday, 4 September 1991

PO-4L1-54

PO-4L1-55

P. Theissen 1, H. Kaemmerer2, 3, U. Sechtem 3, K. Smolarz 1, I. Luhmer 2, M. Jungehiilsing 1, H.C. Kallfelz 2, H. Schicha 1 1Clinic of Nuclear Medicine and 3Medical Clinic I I I - University of Cologne, Joseph-Stelzmann-Str.9, D-5000 Ki~lrgCologne, Germany and 2Dpt of Pediatric Cardiology - Medical School Hannover

P.C.Swift, J.H. Turner, HoF. Oxer, J.P. O'Shea, G.K. Lane and K.V. Woollard. Fremantle Hospital, P.O. Box 480, Fremantle 6160, Western A u s t r a l i a .

MAGNETIC RESONANCE IMAGING OF THE HEART IN P A T I E N T S F O L L O W I N G MUSTARD PROCEDURE F O R TRANSPOSITION OF THE GREAT ARTERIES. In order to assess the function of the ventricles and of the atrioventricular valves and to evaluate function of the atrial switch magnetic resonance imaging (MRI) was performed in 30 children (age: 4 - 21 years, mean 11.5 years) with d-transposition of the great arteries (TGA) following Mustard procedure. Twentythree of the patients (pt) had a simple TGA and seven a vent~icular septal defect. Using gradient-echo (eine) and spin-echo technique the entire h e a r t was depicted in transverse 8-ram-slices without gap. Additionally coronal oblique spin-echo slices showed the atrial anatomy. Pt values were compared to those of 10 healthy volunteers (NL). RVed LVed SV(RV) SV(LV) RVEF [%] LVEF [%] 65+17/70L-_1254&14/72&10 34~8/41!10 3428/41+10 55~12/57_+8 63±7/58~10 enddiastolic volume = ed, endsystolicvolume= es; volumesin ml / m2 body surface (BS); stroke volume = SV;ejeetionfraction =-EF; Pt-values/NL-values+ SD The volume measurements for right (RV) and left (LV) ventricle showed an enlarged RV in all pt and a reduced ejection fraction less than 50% in 10 pt. The calculated muscle mass demonstrated the excessive RV hypertrophy (89 g/ m 2 BS + 21) compared to the LV (36 g / m 2 BS + 14). Hypertrophy with extensive trabeeulation was most pronounced in the RV apex and the RV anterior wall !AW), where systolic wall thickening was significantly (p< 0.004) higher (3.7+1.3 mm/m2BS -+ SD) than at the RV outflow tract (2.3+0.5), at the septum (2.3+1.3), and at the LV postero-lateral wall (2.1+1.0). In 14 pt a systolic turbulence was observed in the pulmonary venous atrium originating from the tricuspid valve, which was quantified and graded as moderate tricuspid regurgitation in 3, mild in 6, and trivial in 5 pt. In 6 pt a significant LV outflow tract (LVOT) stenosis was found because of turbulent blood flow in the LVOT. Atrial obstruction occurred in 6 pt. MRI allows a quantitative insight into the functional status and the morphology of the heart after inflow correction, thus supplementing clinical and eehocardiographie evaluation of the patients.

PO-4L1-56

MYOCARDIAL HIBERNATION CHARACTERIZED BY STRESS THALLIUM SCINTIGRAPHY, TRANSOESOPHAGEAL ECHOCARDIOGRAPHYAND HYPERBARIC OXYGEN. Hibernating myocardium is ischaemic, viable and nonc o n t r a c t i l e heart muscle which has the potential to recover function a f t e r re-oxygenation but which w i l l die i f perfusion is not restored. Stress thallium s c i n t i graphy i d e n t i f i e s ischaemic, viable myocardium and Transoesophageal echocardiography (TEE) shows the cont r a c t i l e function o f myocardium. Combination of these modalities with hyperbaric oxygen therapy (HBO) was performed in a prospective c l i n i c a l t r i a l to define recove r a b i l i t y and thus characterize hibernating myocardium in patients within one week of acute myocardial i n f a r c t ion. Preliminary r e s u l t s of TEE in 17 patients showed improvement in contraction of heart muscle in the region of i n f a r c t i o n immediately following 30 minute HBO at 2 atmospheres which was correlated with stress thallium studies within 24 hours. Thus stress thallium, TEE and HBO in combination can demonstrate hibernating myocardium a f t e r i n f a r c t i o n , and may predict the potential f o r functional recovery to f a c i l i t a t e selection of patients f o r early reperfusion and r e v a s c u l a r i s a t i o n procedures.

PO-4L1-57

I. Umamoto, H. Sugihara, Y. Harada, T. Nakagawa, K. Shiga,

l.Vassiliadis,

H. Katsume, M. Nakagawa Second Department of Medicine, Kyoto Prefectural University of

Hygeia Hospital and Athens Naval Hospital,Greece.

D.Strongilou,L.Colletti

Medicine, Kyoto, Japan A NEW METHOD OF DETECTING SUBENDOCARDIAL ISHEMIA IN PATIENTS WITH AORTIC VALVE STENOSIS WITHOUT CORONARY ARTERY DISEASE USING THALLIUM-201 SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY. Angina in patients with aortic valve stenosis(AS) occurs even in absence of coronary artery disease(CAD). To assess myocardial ishemia in patients with AS without CAD, we studied 10 patients using exercise Thallium-201 single photon emission computed tomography(SPECT). We have found that some patients with AS without CAD have a pattern of transient "dilation" and "wall thinning" of the left ventrile on the immediate post exercise images as compared with 3 hour redistribution images.

We presumed that this findings may reflect subendocardial

ishemia, and analyzed the images quantitatively. Thirty six radii every 10 degrees were generated from the center of the middle myocardial images of the short axis. An area surrounded by thirty six points of maximal count on each radius was calculated in initial and delayed images. Transient dilation index(TDI) as index of dilation was determined by dividing an area in initial image by area in delayed image. TDI > 1.11 (mean+2SD in controls) was defined as subendocardial ishemia. Five patients with AS showed TDI > 1.1 l(Group A), and the remainings showed TDI ~_ 1.11 (Group B). All patients in Group A had both angina and ST depression with exercise. After aortic valve replacement, TDI of two patients in Group A decreased below 1.11. In conclusion, subendocardial ishemia in patients with AS without CAD during exercise is detectable by Thallium-201 SPECT.

DOES DIPYRIDAMOLE INFLUENCE TL-201 LUNG-UPTAKE TO THE SAME DEGREE AS EXERCISE STRESS MYOCARDIAL SCINTIGRAPHY IN CORONARYARTERY DISEASE PATIENTS Increased TL-201 lung-uRtake a f t e r exercise i s a s e n s i t i ve index of ischemia ann correlates with the extent and s e v e r i t y o f the coronary a r t e r y disease(CAD).Dipyridamole has been used as an a l t e r n a t i v e approach to exercise Stress f o r detecting CAD. The purpose of our study is to determine the significance of lung uptake a f t e r D i p y r i damole administration. Peak lung/peak myocardium T1-201 a c t i v i t y index was calculated in 37 pts and 7 controls that had Dipyridamole TL-201 (DMLI) and 36 pts and 8 normals that underwent exercise Stress T~2OL(XMLI).AII pts were catheterized and data were analyzed with ANOVA. NL SVD MVD P DMLl-lnit. 0.42.~0.03 0.42#0.07 0.44~0.07 .01 Def. 0.38±0.08 0.39±0.05 0.38±0.02 XMLI 0.34±0.03 0.37t0.01 0.48_~+0.02 .001 NL: Normals, SVD:single vessel disease, MVD:multi vessel disease, I n i t : I n i t i a l , Del: Delayed Dvpiridamole provoked an increase in mean DMLI from i n i t i a l to delayed images, the d i f f e r e n c e being greater in the MVD group of pts (p<.01). There was also no s i g n i f i cant d i f f e r e n c e between normals and those with diseased coronary vessels. Exercise caused higher values of XMLI f o r pts with CAD, p a r t i c u ! a r y those with severe disease when compared to normals (p<.O01). In conclusion: Increased lung-uptake on i n i t i a l images a f t e r Dipyridamole administration correlates with the presence o f CAD but not with the s e v e r i t y of the disease.

657

Wednesday, 4 September 1991

PO-4L1-58 A.VEBSARI1 P.P.FERRETTI~D.SERAFINII D.SALV@, s . FIORONf,

PO-4L1-59 Honkanen,T, Laitinen R,

Lantto T,

and

Vorne

N.

G.CASALI, 4 l-l°Radiology 3-2°Cardiology

and Nucl.Med.Dept.

P~ij~t-H~me

2-Physics Dept.

Dept. 4-1°Cardiology

THREE-DIMENSIONAL DISPLAY IN THE EVALUATION OF MYOCARDIAL PERFUSION BY SPECT:COMPARISON WITH BULLSEYE REPRESENTATION. The direct 3D display of an organ can show anatomy more easily than a mental reconstruction of the morphology from individual slices. In this study we .compare 3D display with Bullseye representation in pt§ wiZh CAD diagnosed by means of angiography. 47 p t s . ( 4 1 M - 6 F;mean age 57,2 years) were studied. Stress and rest SPECT images were collected after i.v. injection of ii0 NBq of TI20L at peak exercise, using the following technique: rotation angle of 180°(from RAO 450 to LPO 45°),32 views, 64x64 matrix, LEGP collimator. In all cases, the same tomografic data were elaborated using Bullseye and 3D methods. The 3D display was integrated with the analysis of the images obtained from the rest-stress subtraction. The analysis of tbe results shows no significant differences in the sensitivity and specificity of the two methods in identifying the stenotic vessels (see table). However the 3D display allows a better evaluation of the position and extent of ischemie or necrotic lesions, particularly those near the base and the apex. The rest-stress subtraction is decisive in identifying non transmural ischemic lesions.

SENSITIVITYtSPECIFICITY1 LAD BULLSEYE 87% 3D WITHOUT SUBTRACTION 77% 3D WITH SUBTRACTION 90%

LCX 83% 53% 87%

Central

Hospital,

Lahti,

Finland

Dept. REGGIO E.ITALY

RCAILAD LCX RCA 1 95%[75% 82% 50% / 87% 87% 100% 62% 97% 75% 82% 62%

Tc-99m-LABELLED PLATELETS AND In-11I-LABELLED MONOCLONALANTIFIBRINANTIBODIES IN LEG THROMBOSIS

Fourteen patients (pts) (6 female, 8 male) with suspicion of thrombosis in lower extremities were imaged both with autologous Tc-99m-HMPA0-1abelled platelets (Tc-PLT) and In-111-1abelled monoclonal ant i f i b r i n antibodies (In-MoAbs-F) at the same day. 7 pts were anticoagulated with heparin during the study. Presence or absence of thrombosis was verified by contrast venography (CV) (13) or US (1). Tc-PLT (mean dose 185 MBq) was given f i r s t and half-an-hour l a t e r In-MoAbs-F (mean dose 52 MBq) intravenously. Images of the lower extremities in anterior and posterior projections were obtained with a computer connected gamma camera at 10-20 min (blood pool phase), 2 h, 5 h, and 18-22 h after the injection of each imaging agent using a standard low energy collimator in Tc-PLT-imaging and a standard medium energy collimator in In-MoAbs-F-imaging. Image quality was better with Tc-PLT than with InMoAbs-F. The results with both agents were in agreement with CV ahd US in all pts without heparin. Tc-PLT uptake was greater than In-MoAbs-F uptake in pts without anticoagulation. Heparin treatment inhibited significantly the uptake of Tc-PLT but not the uptake of In-MoAbs-F. Out of the 7 heparinized pts 3 were true positive (TP) and 4 false negative (FN) with TcPLT and 5 TP and 2 FN with In-MoAbs-F. We conclude that both Tc-PLT and In-MoAbs-F are suitable agents for the detection of deep venous thrombosis especially in pts without anticoagulation.

PO-4L1-60

PO-4L1-61

Zanco P.L.~ Borsato N.~ Saitta B.~ Suzzi G . L ~ Candelpergher G%~ Celegon P~* *Nuclear Medicine Service, **Division of Cardiology, Castelfranco Veneto Hospital

R. Zimmermann. P. Stokstad, B. Bubeck, M. Kapp, U. Grethe, B. Rauch, W. Ktibler, H. Tillmanns. Departments of Cardiology and Nuclear Medicine, Universities of Heidelberg and Giegen, Germany

RETROSPECTIVE STUDY ON 99mTc MIBI REST HYPOCAPTATION PATIENTS WITHOUT EVIDENCE OF MYOCARDIAL NECROSIS.

IN

To evaluate the incidence and the meaning of rest uptake defects in myocardial SPECT using 99mTc-sestamibi, we reexamined rest and stress images of 163 patients (50F,ll3M,aged 19-72, medium 54-yrs) without clinical evidence or EKG signs of previous myocardial necrosis. In the rest study, the distribution of sestamibi was homogeneous in i06 subjects ( group 1 ). The other 57 patients showed ( group 2 ) a decreased uptake of 30% or more that we consider significant compared with the maximum myocardial count. The two groups had no differences in age and sex. The women presented only lower uptake in the antero-apical wall, with an incidence of 18%, whereas we found rest defects in 48 men (42%), most of them localized in the inferior wall (44/48). In the group l, the stress images showed reduced perfusion in 2B males (out of 65), that is 43%; while in the group 2 we found it in 22 males (out of 48), with a percentage of 48%. In conclusion, a rest defect i s a frequent finding in sestamibi SPECT without myocardial necrosis; moreover it is more easily found in men, whose inferior wall is almost always affected. In our opinion, rest defects have no predictive value for stress ischaemia.

RESPONSE OF POSTSTENOTIC MYOCARDIAL TL-201

AND 1-123 PHENYLPENTADECANOIC ACID UPTAKE AND CLEARANCE TO TREATMENT WITH GALLOPAMIL The present study was performed to investigate the effect of chronic treatment with the calcium antagonist gallopamil on myocardial perfusion and fatty acid utilization. Twenty-two patients with angiographieally documented coronary artery disease underwent consecutive dual-isotope studies following simultaneous injection of 80 MBq thallium-201 (T1-201) and 200 MBq iodine-123 phenylpentadecanoic acid (IPPA) after symptom limited stress test. Radionuelide studies were performed after 1 week placebo treatment (baseline), 4 weeks after oral treatment with 3x50 rag/die gallopamil, and again after 1 week double-blind treatment with gallopamil or placebo. As compared to baseline, initial uptake of both tracers in poststenotic myocardial segments was significantly improved after gallopamil treatment (TI-201:+3.8 + 7.8%, p = 0.021; IPPA: +5.3 + 11.4%, p = 0.016). Furthermore, poststenotic IPPA clearance tended to increase (+6.2 + 9.5%, p = 0.094) indicating a more rapid fatty acid utilization after treatment. In the final double-blind phase, uptake of both tracers further increased in the subgroup of patients receiving gallopamil, and slightly decreased in patients receMng placebo. Thus, in poststenotic myocardium chronic treatment with gallopamil provokes an improvement of both regional myocardial perfusion and fatty acid utilization.

Abstract PO-4L1-61A see page 688

658

Wednesday, 4 September 1991

PO-4R1-2

PO-4R1-1 M. Baehre, K. Walter, P. Vieregge 1, J. Bauer, S. Pilgrim, E. Richter Clinic of Radiotherapy and Nuclear Medicine, 1Clinic of Neurology, Medical University of Luebeck, D-2400 Luebeck, Germany MULTIPLICATIVE ITERATIVE SPECT RECONSTRUCTION (MISR): ENHANCED INFORMATION CONTENT COMPARED WITH FILTERED BACKPROJECTION (FBP) Purpose of the study: Previously published investigations based on qualitative visual evaluation of brain SPECT studies had indicated an enhanced detectability of details and outline definition in MISR tomograms compared to FBP results. In order to verify a potential gain in information content more objectively, we performed a multiobserver comparison of MISR and FBP with statistical evaluation of data. Patients and methods: 99mTc-HMPAO brain SPECT studies of 27 patients with neurologie diseases were acquired in matrices of 128 x 128 pixels. Reconstruction using MISR, FBP and, after frame condensation, FBP in 64 x 64 matrices resulted in three sets of 16 transversal slices per patient. Each of these 81 sets was normalized to its count maximum. All sets of tomograms were rated at a random sequence by five experienced, independent observers using a three-grade scale. The degree of reduction in regional tracer uptake was judged in 70 regions resulting in a total of 28350 ratings. Statistical evaluation was performed using a distribution-free rank test. Results: Imaging of reduced tracer uptake in MISR tomograms was significantly superior to both FBP versions in 40 and 6 regions, respectively (p < 0.05). When uptake ratings judged as "questionable" were excluded superiority of MISR results came off even more distinctly. Conclusions: Compared to FBP the applied MISR algorithm provided a considerable gain in brain SPECT information. Thus, when used in the clinical setting, MISR may serve as a useful means for routine brain SPECT application.

J.P. Binon, E. Delcourt, R. Calay, R. Amir C . H . U . A . VESALE

6110 Montigny le Tilleul, BELGIUM

VALIDATION OF A NEW SEGMENTATION METHOD COMPARISON BETWEEN GRADIENT AND DENSITY

BASED

ON

Most commonly used methods of semi-automated (extraction of object} a r e t h e fixed t h r e s h o l d (FT) and gray level histogram (GLH). H o w e v e r t h e s e m e t h o d s have s h o r t c o m i n g s in case of important

segmentation

background. The aim of this study is to demonstrate that this separation will be improved by performing a new algorithm, the gradient density filter (GDF) which separates object from background pixels by comparing their gradient with their density (D). >[ a . e- b ' D (x,y) For each organ pixel ix,y): I G(x,y) where a and b are system and preprocessing dependent. The area measurement needs two embedded corrections by least-squares linear regression analysis: the inner one for background variation (r = -0.905, error of estimate = 1.0%) and the outer one for influence of the size of the organ (r = 0.999). We e v a l u a t e d the reproducibility of t h e semi-automated segmentation methods by comparing their relative standard deviation in a series of phantoms (n = 50) with three different areas (28, 38 and 56 cm 2 ) and background varying from 0 to 66%. phantom quality

N

GDF

GLH

uniform non-uniform

42 8

1.61 0.51

2.12 3.81

FT30% FT40% FT50% 4.35 5.36 7.20 4.44 10.51 11.39

For a clinical evaluation, we compared the same methods in a series of 42 thyroid studies (each one including acquisitions 6H and 24H after injection of

mean difference % )artial segmentation % % [ailure due to bkg

GDF

GLH

4.31 8.5 0.0

5.49 14.9 i.i

FT30% FT40% FT50% 5.29 16.0 2.1

7.54 29.8 4.3

9.17 50.0 4.3

We conclude that in planar studies, partial segmentation is minimal and reproducibility as also robustness to background are optimal with GDF method.

PO-4R1-3

PO-4R1-4

AUTOMATIC REORIENTATION AND CENTERING OF IN TL-2Ol 5PECT. J.C. Csuvin, THE LEFT VENTRICLE 3.y. Boire, J.C. Maublant, M. Z a n c a , V. B o u s q u e t , A. Veyre. Centre Jean Perrin and ERIM, INSERM U 71, C]ermont-Ferrand, France and 5OPHA MEDICAL, Buc.

L. C i n o t t i , P. L a n d a i s , D. Le Bars, P. M i l l e t , O. R o u s s e t , J.P. B a z i n * , R. D i P a o l a * . CERMEP, 69003 Lyon, *INSERM U66, Institut Gustave Roussy, 94800 Villejuif, FRANCE.

In m y o c a r d i a l SPECT, centering and r e o r i e n t a t i o n of t h e l e f t v e n t r i c l e r e m a i n s a c r u c i a l step in i m a g e c o m parison and in most of the quantification procesMngs. The a u t o m a t i z a t i o n of t h i s step w o u l d i m p r o v e t h e q u a l i t y and t h e reproducibility of the images interpretation. A m e t h o d based on t h e 5D m o d e l l i n g of t h e l e f t v e n t r i c l e by a q u a d r i c is p r e s e n t e d . The r e c o n s t r u c t e d transverse sections are masked by a s p h e r i c a l region of interest in o r d e r to e l i m i n a t e the s u r r o u n d i n g a c t i v i t y . T h e m y o c a r dial s e c t i o n s a r e b i n a r i z e d and, using m a t h e m a t l c a ] morphology, the 3D left ventricle is t r a n s f o r m e d into its 3O s k e l e t o n . The s k e l e t o n is t h e n f i t t e d by t h e l e a s t s q u a r e m e t h o d to t h e g e n e r a l e q u a t i o n of a q u a d r i c . T h e f i t t e d s u r f a c e m a y be an e l l i p s o i d , a h y p e r b o l o i d or a p a r a b o l o i d . The long axis o f t h e q u a d r i c is a s s u m e d to be t h e long axis of the left ventricle. From the coefficient of t h e quadrie, the horizontal (HA) and vertical angles (VA) and t h e c o o r d i n a t e s o f the c e n t e r in t h e frontal view (5g,Tr) are calculated. The m e t h o d was a p p l i e d to a s e r i e of 30 c o n s e c u t i v e s t r e s s and r e d i s t r i b u t i o n studies. The measurements were manually and a u t o m a t i c a l l y performed t w i c e by t w o o p e r a t o r s . T h e m a i n r e s u l t s a r e as f o l l o w i n g S/N: s i g n i f i c a n t or no s i g n i f i c a n t d i f f e r e n c e , pq13.05 manual

automatic r

HA VA 0g Tr

S S N S

0.90 0.79 0.97 0,98

manual r

N

N N N

1.00 1.00[ I 1.00] 1.00 I

vs a u t o m a t i c lowest

s 5 0 N

r

0.82 0.76 0.96 0.98

In conclusion the reproducibility of automatic centering and raorientation proved to be definitely superior to the manual method.

VALIDATION OF FACTOR ANALYSIS IN POSITRON EMISSION TOMOGRAPHIC IMAGE SERIES FOR QUANTITATIVE MODELLING. In d y n a m i c P E T i m a g e s , t h e r e s o l u t i o n merges compartments together, diminishing the modelling q u a l i t y . We t r i e d t o a p p r e c i a t e t h e improvement brought by Factor Analysis of Dynamic Structures (FADS) to q u a n t i t a t i v e d a t a m o d e l l i n g . We simulated biological kinetics (time constants = ll0, 20 a n d i0 m i n u t e s ) using simultaneously 18F, IIC and 13N. Three experiments were performed: i) 18F a n d IIc in s e p a r a t e d v i a l s ; 2) 18F, IIc a n d 13N in s e p a r a t e d v i a l s a n d 3) v a r y i n g k n o w n c o m b i n a t i o n s of t h e t h r e e i s o t o p e s in t h e v i a l s . D a t a w e r e c o l l e c t e d in l i s t - m o d e over 2.5 hours using a TOF-PET scanner and 5 minutes image series were reconstructed. In e x p e r i m e n t s 1 a n d 2, t h e c l a s s i c a l region of interest (ROI) method provided the best results. In e x p e r i m e n t 3, the ROI method provided the expected time constants within 2.5 to 6.0% in t h e v i a l s c o n t a i n i n g p u r e 18F, llc or 13N but uninterpretable combinations of exponential decays in the other vials. Conversely, FADS correlated well with the known kinetics, detecting the expected time constants within 1.9 to 5.4% and also the different percentages of c o m b i n a t i o n s in a l l t h e v i a l s ( y = . 9 4 4 x + l . 8 6 9 , r = . 999, p < . 0 0 0 1 ) . F A D S a p p e a r s to be a t o o l to p r e p a r e d a t a f o r compartmental analysis by decorrelating informations and providing accurate estimations of t h e p r o p o r t i o n s of c o m b i n e d c o m p o n e n t s .

659

Wednesday, 4 September 1991

PO-4R1-5

PC-4R1-6

A. COPPENS, P. MARESCHAL, C. MICBEL, A. BOL, J. NELIN. University of Louvain, Louvain-la-Neuve, Belgium.

A, DOBBELEIR, P.R. FRANKEN, J, VANDEVIVERE. Middelheim General Hospital, Antwerp, Belgium.

XTOPO, AN OBJBCT-OP~I~ITEDPROGRAM FOR IMAGE ANAL¥SIS. The Xtopo program is a new object-orlented program designed to process interactively medical images. Xtopo is written in C++ and is using two objects libraries : OOPS, the Object-Oriented Program Support Class Libraries, which is a collection of classes similar to those of Smalltalk-80, and InterViews, a C++ Graphical Interface Toolkit based on the X Window System. Xtopo is running on a DECstation 3100 with the Ultrix operating system. It is built on Idraw, a graphical editor from the InterViews distribution. The program has been developed to manipulate different image modalities such as NMR, PET and SPECT. The processing is performed with direct user interfaces. It consists in creation of region of interest, their manipulation and integration, production of time activity curves, operations on images (mathematical diadic and monoadic operations such as filtering, edge detection, enhancement, sub- and re-sampling), image profiles (orthogonal, polygonal and sectorial), and color table manipulations (thresholding, compression, bias). The output (text and PostSerlpt graphics) can be reused by other applications for further processing (such as tracer modeling). Images, ROIs and results are built as objects (i.e. a set of data, a set of applicable functions and their properties) in a hierarchy of classes, which allows easy upgrades in any object definition.

A NORMALISATION METHOD FOR QUANTIFICATION OF MYOCARDIAL PERFUSION IMAGES INDEPENDANT OF NORMAL TISSUE LOCALISATION. Currently the patient's bullseye is normalised to a normal data bank file using the maximum pixel value of each circumferential profile or to the most normal of different regions after dividing the patient's by the normal bullseye. We propose a normalisation method for quantitative analysis of Tc99m SESTAMIBI myocardial pedusion tomograms which searches for normal values all over the image without assumption of Iocalisation. Gender-matched rest and stress normal and S.D. bulls-eye images were established in 40 patients (20 men and 20 women) with a low(< 5%) likelihood of coronary artery disease. The pixel by pixel ratio of the bullseye of normal patients to the normal database file was calculated and a gaussian shape ratio distribution obtained. In normal patients the 95% confidence interval of this ratio was 1.00 +- 0.13. Patient normalisation was carried out based on this measured normal ratio distribution: divide patient's bullseye by gender-matched normal file find +2S.D. of normal values (for gauss distribution = value of 97.5% highest pixel after classification in order of size) find -2S.D. of normal values = +2S.D. value X 0.87/1.13 calculate mean normal value between -2S.D. and +2S,D. values divide ratio image by mean normal value Patient normalised image was then compared to gender-matched S.D. image and the percentage of ANT,INF,LAT.SEPT,APEX and TOTAL surface (each slice weighted for relative contribution of LV mass) deviation calculated. Seventeen patients who undergone coronary arteriography and 12 patients with low probability of CAD were prospectively incorporated in a pilot study to define criteria for the identification and localization of pedusion defects. This method had a 89.5 % sensitivity and a 45.2 % specificity for the detection of individual coronary stenosis.

PO-4R1-7

PO-4R1-8

I. F~ides, I. Felde Korvin Hospftal Budapest, Hl~ngary

D. Gaqnon, L. Laperri~re, N. Pouliot, J. Grdgoire, A. Arsenault. Montreal Heart Institute, 5000 E. Belanger, Montreal H 1T 1 C8, CANADA

NEW TEt3~IQUE FOR DECONVOLUTION ANALYSIS. The mostly accepted deconvolution procedures in nuclear medicine usir~ matrix algorithm or Laplace trar~fo~ation continue to be a problem. A new deconvolation method has been developed based on Widrow's adaptive filter algorithm. %his algorithm is under proper conditions convergent and using the input ar~i output si~]als derives the impulse response function. Advantages : l~Xhis method compared to the widely applied Fourier trar%sformation needs no matrix , is considerably faster and the deconvolution can be performed on a small computer of limited capacity of memory. 2.The method is inser~ible to counting errors contaminating the input and output data. This new deconvolution technique was succesfully used for anal>sing patient data in perfusion (liver, kidney), parenchymal extraction (liver-IDA derivate) and transport system (biliary tract) studies. Widrow B.,~ et al. : Noise subtracting filter Study A.D. 767717/2 Goverment Reports 1973.

660

THE USE OF HOLOSPECTRAL IMAGING FOR DOSE-TIME OPTIMIZATION IN NUCLEAR MEDICINE ACQUISITIONS.

It has been demonstrated that Holospectral Imaging (HI) can be used efficiently to analyze, describe and compensate for scatter contamination in nuclear medicine images. The HI technique, based on a Principal Component Analysis (PCA), is using different ratios of eigenValues. Evolution of these ratios, in terms of total variance, quantum noise, scatter fraction, instrumentation uniformity and others, can 61so be used to monitor the global image characteristics. Preliminary results using MonteCarlo simulation show a very good correspondence between the inferred image quality (ratios of eigenvalues) and actual imaging parameters (number of count and scatter fraction). It is obvious that, for the same object and dose, the total image variance is inversely proportional to the source depth. But the time to get the same object-to-non-object ratio is also depth-dependent. In other words, by monitoring the HI data, it is possible to predict when an "acceptable" percentage of the ultimate object-to-nonobject ratio is achieved. Beyond that point, gain in the image information would be marginal. For instance, additional variance brought in by passing from IOOK events to 12OK events is 2 % when the object is 5cm deep while it is still more than 4 % with the object at 2Ocm. An acceptability criterion could then be defined in terms of information increase rate. We believe that a better description of image quality could be instrumental to a better dose/time management in nuclear medicine.

Wednesday, 4 September 1991

PO-4R1-9 G.J.GILLEN and A.T. ELLIOTT

PO-4R1-10 E.GREMILLET, A.CHAMPAILLER. Centre

d'Imagerie

Nucl6aire.

St-Etienne. F R A N C E West of Scotland Health Board's Department of Clinical Physics, Glasgow AN INVESTIOATION OF THE MAGNITUDE AND CAUSES OF COUNT LOSS ARTEFACTS IN SPECT IMAGING

ALGORITHMS DEPTH-WEIGHTED

Count loss artefacts can he a problem in clinical SPECT imaging. The most commonly encountered example of this occurs when sections are taken through the femoral heads in skeletal studies of the pelvis. The count loss artefacts can easily be mistaken for the photon deficient areas diagnostic of avascular necrosis. The aim of this investigation was to provide an explanation of the mechanism of this phenomenon. From some simple phantom studies it was identified that the count losses were associated with the presence of a high dynamic range in the projection data. Further information was obtained from simulation studies. It was found that the count loss phenomenon is caused by the combined effects of the presence of a high count density area and a structure with a relatively high attenuation level. The reduction in counts in projection lines which pass through both the high attenuation area and the high count density area can be large in proportion to the lower count density structures. Thus when the back projection is performed significant errors in the count values of the lower count density structures can occur. An appreciation of the presence: magnitude and mechanism of this effect is important if erroneous clinical findings are to be avoided.

Depth-weighted maximum projection (DWMP) g i v e s an e f f i c i e n t 3D d i s p l a y of S P E C T d a t a . We d e s c r i b e h e r e s o m e a l g o r i t h m t i p s a l l o w i n g r o u t i n e c l i n i c a l u s e of DWMP. 1 . V o l u m e r o t a t i o n is t i m e c o n s u m i n g : for one r o t a t i o n a p p l y i n g D W M P f r o m f r o n t (F) t o b a c k (B), r i g h t (R) to l e f t (L), B to F, L to R generates 4 a n g u l a r v i e w s at K / 2 i n t e r v a l s . T h u s n-i r o t a t i o n s g i v e 4n v i e w s . 2.Iterative rotations may blur data: rotations must always be performed from original data. To save computer memory, rotations should be performed on single transversal slices a n d a c t u a l D W M P on r o w s a n d / o r c o l u m n s of t h e r o t a t e d slice. 3.Angular views around other axes than the vertical axis can easily be o b t a i n e d , eg around the horizontal frontal axis: first perform volume,

FOR

ROUTINE MAXIMUM

a +z/2 f r o n t a l then apply the

COMPUTATION PROJECTION.

OF

r o t a t i o n of t h e w h o l e regular DWMP program,

finally rotate a l l t h e v i e w s of - K / 2 . For most computers, this adds only a few seconds to t h e t o t a l t i m e . Using tips 1 and 2, our Forth program (68020/16MHz computer), requires less than 2 m i n a n d o n l y 776 k b y t e s of m e m o r y to c o m p u t e 32 a n g u l a r v i e w s of a 6 4 x 6 4 x 6 4 c u b i c d a t a set (16 b i t s / p i x e l ) . U s i n g t i p 3, b i - o r t r i plane cine displays are easily obtained by c o n c a t e n a t i n g 2 or 3 sets of v i e w s .

PO-4R1-11

PO-4R1-12

L.Hahn, D.Swerhone, R.Sloboda* R.Kloiber, A.Crawley. Department of Radiological Sciences and Diagnostic Imaging, Foothills Hospital, Calgary, *Cross Cancer Institute, Edmonton, Alberta, Canada

NEBBELINCR D. ,BOURGEOIS F. Centre Hospitalier d.Bracops ,Service des Radioisotopes

HOLOSPECTRAL IMAGING SCATTER CORRECTION TECHNIQUE APPLIED TO SPECT Removal of scatter from SPECT images can be done using a number of methods. One of them is Holospectral Imaging (HI) technique, based on principal component analysis (D.Gagnon et al., 1989). Assuming that the image acquired by gamma camera is a combination of photopeak information, scatter and noise one- can separate the components using the whole spectrum and obtain scatter free images.

AN ALTERNATIVE METHOD TO VISUALIZE QUANTITATIVELY DIFFERENCES COMPARING TWO TOMOGRAFHIC HEART STUDIES.

To avoid all problems with imperfections introduced by the gamma camera when recording the whole spectrum, the Monte Carlo (MC)simulated data have been used. Simulations were made for a water filled cylinder with uniformly distributed activity of Tc-99m, containing 7 "hot" spheres with the radii of 2 cm, 1.5 cm, 1 cm and 0.5 cm located at different distances from the centre of the cylinder. Specific activity of "hot" spheres was five times higher than that of the cylinder. Using MC code 64 angular projections in 64 x 64 matrix have been generated for 7 and I0 windows between 55 and 155 keV, with a window width of 14 keV and i0 keV, respectively. We found significant improvement of contrast and of the ratios of specific activities between "hot" spots and surroundings in reconstructed SPECT images, after application of HI technique. However, the further improvement of contrast and these ratios is negligible when increasing the number of windows from 7 to I0. l. Gagnon D., Todd-Pokropek A., Arsenault A., Dupras G.: Introduction to Holospectral Imaging in Nuclear Medicine for Scatter Subtraction, IEEE Trans. Med Imaging, Vol. MI-8, pp. 245-250, (1989)

(BRUSSELS)

BY

In order to compare SPECT cardiac studies obtained either at rest and at stress, or at different times ( e.a. pre and post CABG or PTCA ) as well as using different isotopes or labelled molecules (e.a. thallium and MIBI or NIBI and FFA ), a method - alternative to Bullseye - was developped that allows a direct visuallsation of the differences in the relative distribution of the tracers. First of all reorientation and reconstruction of both acquisitions are performed so that short axis slices perpendicular to the long axis of the heart are obtained. A circular EOI, whose center correspond with the long axis through the heart, is placed over both series of 16 reconstructed slices. Those EOI are divided into 8 equal sectors, so that 2 times 8 series of 16 data are obtained, representing the activity (counts) per sector and slice. Each eerie of 8 x 16 data is normalized to 100%. These results are compared sector by sector, slice by slice and put into S histograms, translating the differences observed by comparing the two series of reconstructed slices. HIBI or These first results allow to compare, for instance, thallium studies obtained at rest and st stress. But for comparison of perfusion and metabolic studies, a second type of analysis was developped where it was assumed that the relative uptake of the metabolic tracer in the slice-sector of 100% relative activity with the perfusion tracer was "normal" and thus equal to 1O0~. Metabolic activities are then expressed with reference to this slice-sector and compared to the corresponding perfusion values. This analysis thus gives the metabolic state as a function of the perfusion. The differences, whether the value of the first or secoad eerie is the greatest, are represented on different colors (i.e. GREEN if the reference eerie > second eerie and REB if the reference serie < second eerie). Samples of results so obtained will he presented comparing reststress studies with Mini and perfusion study ( with NIBI) to metabolic study ( with 123I-Ortho-IPPA ).

661

Wednesday, 4 September 1991

PO-4R1-13

PO-4R1-14

H . S t e i n m e t z I, Y.Huang 1, H=!lerzog 2, R.J.Seitz t

S. Hirose, M. Ide, Y. Suzuki, Y. Goto Tokai University, School of Medicine, Isehara, Japan

(1) D e p a r t m e n t of Neurology, H e i n r i c h - H e i n e - U n i v e r s i t y of Diisseldorf, and (2) I n s t i t u t e of Medicine, R e s e a r c h C e n t e r Jtilich, F,R.G. COMPUTATIONAL IMAGE DATA

ALIGNMENT

OF

MR

AND

PET

BRAIN

Until now, t h e t o p o g r a p h i c a l a n a l y s i s of p o s i t r o n e m i s sion t o m o g r a p h y (PET) i m a g e s is u s u a l l y b a s e d on a n a t o m i c a l i n f o r m a t i o n from s b r a i n a t l a s . However, a t l a s e s c a n n o t a c c o u n t for t h e m a r k e d i n d i v i d u a l v a r i a t i o n in b r a i n s h a p e and g y r a l p a t t e r n , nor do t h e y a p p l y to s t r u c t u r a l l y a b n o r m a l b r a i n s . T h e r e f o r e , we h a v e d e v e loped a m e t h o d for t h e c o m p u t a t i o n a l a l i g n m e n t of h i g h r e s o l u t i o n m a g n e t i c r e s o n a n c e (MR) image d a t a w i t h PET in t h e s a m e s u b j e c t . Three orthogonal f r o n t - t o - b a c k d i s p l a y s of t h e 3D h e a d s u r f a c e a r e g e n e r a t e d from e a c h d a t a s e t to d e t e r m i n e head orientations in t h e 3D s p a c e . Between-method a l i g n m e n t of two d a t a s e t s is t h e n a c h i e v e d by i t e r a t i v e m a t c h i n g of t h e f r o n t - t o - b a c k - d i s p l a y s . A v a l i d a t i o n s t u d y u s i n g t h e A l d e r s o n " a v e r a g e man" p h a n t o m d e m o n s t r a t e d a h i g h a c c u r a c y of t h i s p r o c e d u r e . The p h a n t o m ' s h e a d w a s e x a m i n e d w i t h MR (Siemens M a g n e t o m 1.5 T) and PET ( S c a n d i t r o n i x PC4096, 8 r i n g s , 7ram s l i c e t h i c k n e s s , 2ram p i x e l size). T r a n s m i s s i o n PET s c a n s were u s e d for t h e m a t c h . I n s e r t i o n holes of t h e p h a n t o m were f i l l e d w i t h w a t e r for MR, or 68Ga f o r PET. The m a t c h i n g a l g o r i t h m c o n v e r g e d v e r y f a s t with c o m p u t a t i o n t i m e s from 2 to 10 m i n u t e s . The m a t c h w a s h i g h l y a c c u r a t e w i t h a m e a n r e s i d u a l m i s f i t of t h e i n s e r t i o n holes of only 2.8ram b e t w e e n MR and PET. T h u s , a c c u r a c y d e p e n d e d s o l e l y on t h e i m a g e r e s o l u t i o n of PET. The i n t e g r a t i o n of MR a n d PET allows i n d i v i d u a l l y - b a s e d s t r u c t u r a l - f u n c t i o n a l c o r r e l a t i o n s . T h i s will be of p a r t i c u l a r i m p o r t a n c e for PET s t u d i e s on h i g h e r c o g n i t i v e f u n c t i o n s , and for s t u d i e s on p a t i e n t s w i t h s t r u c t u r a l b r a i n l e s i o n s or d e g e n e r a t i v e d i s e a s e .

Kanagawa,

NON-INVASIVE ASSESSMENT OF THE LEFT VENTRICULAR PRESSURE TO VOLUME RELATIONSHIPS DURING EJECTION PERIOD The left ventricular (LV) pressure to volume relationships are very sensitive parameters for evaluation of the LV function. For measurement of LV pressure in an entire cardiac cycle, an invasive method is always needed, however during ejection period, the LV pressure is known to be similar to that of aorta and radial artery. We have developed a new system for non-invasive assessment of LV pressure to volume relationships, in which the LV volume is estimated by radio-nuclide ventriculography (RNVG) and the pressure is estimated simultaneously by radial arterial pressure. The ECG-gated R~IVG was performed by a single cardiac probe system (OMNISCOPE, Aloka Co., Ltd., Japan) and data were collected every i0 msec. The radial arterial pressure was measured every l0 msec by a tonometry system (CBM2000, Colin Electronics Co., Ltd., Japan). These data were transferred to the personal computer (PC-9801 VM2, NEC Co., Ltd., Japan) through RS-232c cable. Then, the pressure to volume curves during ejection pressure to volume curves during ejection phase was generated automatically. The peak ejection pressure to volume value was calculated from this curve. Moreover, the new parameter called the ejection rate of change of power (ERCP) can be easily calculated. With this new system, the LV pressure to volume relationships during ejection period can be easily assessed non-invasively. These parameters are very useful for the evaluation of the effect of the drugs on the LV performance.

PO-4R1-15

PO-4R1-16

KB Hosie, *LK Harding, *AB Mostafa, *NJ TuIley, *NB Smith, and MRB Keighley Department of Surgery, Queen Elizabeth Hospital, BI52TH *Department of Physics & Nuclear Medicine, Dudley Road Hospital, BI87QH

Karin Knesaurek, University of Rochester Medical Center, P.O. Box 620, Rochester, New York 14642, U.S.A.

USING ARITHMETIC OR GEOMETRIC MEAN TO DETERMINE ORGAN COUNTS - A PROBLEMOF SCATTER I t is generally accepted t h a t the geometric mean overcomes problems of a n t e r i o r - p o s t e r i o r movement during Nuclear Medicine studies, but some authors have argued that the arithmetic meal is as r e l i a b l e . Using a stomach phantom in a water bath the gamma camera whole f i e l d geometric mean 9 c~unt shows a 14% maximum v a r i a t i o n with depth f o r Tc , but the arithmetic mean 129% v a r i a t i o n over the same depth range (2-28 cm). These r e s u l t s suggest t h a t the arithmetic mean organ counts are not r e l i a b l e . However, in 30 patients there was l i t t l e v a r i a t i o n in c o e f f i c i e n t of v a r i a t i o n of whole f i e l d of view counts using e i t h e r geometric mean (4.5%) or arithmetic mean (5.0%), probably due to the small v a r i a t i o n of depth encountered in p a t i e n t studies. In some patient studies there is no emptying at the time of peak stomach counts. Despite taking the geometric mean of the stomach counts these are always less than the whole f i e l d of view counts, the discrepancy being due to scattered counts from the stomach being detected outside i t s ROI. Applying a s c a t t e r correction derived from the above phantom experiments, the average discrepancy of -24.4% (range -9 -> -45) was reduced to -0.75% (range -12.7 -> +9.8). Geometric mean l a r g e l y overcomes problems of depth change, but additional correction f o r scatter is needed f o r q u a n t i f i c a t i o n of organ counts.

662

INTERATIVE A ~ A T I O N TRANSMISSION DATA

CORRECTION IN SPECT WHICH USES

To perform accurate attenuation correction in SPECT one has to know the distribution of attenuation coefficients. This distribution can be obtained frcm CT study or transmission study using the same gamma camera. In our work, data obtained frc~n transmission/~aission SPECT study has been used in an iterative reconstruction process with incorporated attenuation correction. Gradient and conjugate gradient iferative methods were used. Conjugate gradient method has been also modified to handle noisy projection data. This modification was based on additive noise. The results of our study shows that very often X 2 is not a good parameter for obtaining optimal image, especially for transmission noisy data. Even the modification based on additive noise, in conjugate gradient iterative method, has not significantly improved either t h ~ speed of iteration or quality of the reconstructed image. The stepping rules for iterative processes have to be carefully examined, because the solutions for higher number of iterations, and accordingly lower %2, have tendency to "blow up".

Wednesday, 4 September 1991

PO-4R1-17

PO-4R1-18

C-S. Koh, B.Y. Cho Hospital, Korea

C. Kwark, D.$. Lee, J-K. CLung, M.C. Lee, and B.G. Min. Seoal National University 28 Yunkun-dong, Chongno-gu, Seoul, 110-744,

B.J.Krause, M.H.Bourguignon, H.Valette, B.Bendriem, C.Raynaud, G.HOr and A.Syrota. SHFJ, Orsay, FRANCE and J.W.Goethe Universit~t, Frankfurt, GERMANY,

ON THE LOCAL TISSUE ATTENUATION C O R R E C T I O N IN SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY The objective of this study is to develop a technique for the enhancement of resolution of reconstructed slices in single photon emission computed tomography (SPECT), which can correct the attenuation of gamma rays inherent in SPECT images based on the stochastic modeling of attenuation process. While the commonly used methods utilize simple linear models from the predefined body contour or slightly modified version of one or more of them, the extended Prony approach is really data dependent and takes as much distribution to attenuation as possible from the individual portion of investigated tissues and organs depending on the block size in image segmentation. With 64 X 64 imaging matrix and 5 X 5 block size, this approach produces sufficiently correct estimation of attenuation inside the small uniform area, which leads to image enhancement of reconstructed slices compared to the conventional methods. The assumption on this method is that attenuation coefficient is constant inside the small block selected as local tissue, and scattering characteristics follows widely known fixed statistics. For the practical application of our study to attenuation correction, the backprojected slices of images are just postprocessed with the calculated distribution of local tissue attenuation. The time required for postprocessing is acceptably short and can be shortened with additional array processors. Most of the attenuation effects were corrected not only in computer simulation but in SPECT phantom experiment. Clinical studies demonstrate significant potential of the pr6posed method in the investigation of brain and heart.

HIGH RESOLUTION-LOW COUNT RATE SPECT IMAGES IN QUANTITATIVE BRAIN TOMOGRAPHY.

PO-4R1-19

PO-4R1-20

J. L. Lear, J. P. Pratt, A. J. Feyerabend. Nuclear Medicine (A034), University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO, 80262

J.C.

CLINICAL EVALUATION OF A MACINTOSH II SYSTEM FOR ACQUISITION, PROCESSING AND COMMUNICATION OF GAMMA CAMERA IMAGES Having demonstrated the feasibility of hardware to digitize gamma camera outputs directly into Macintosh II computers (presented at EANM 90), we developed a clinical software package in C and assembly language for processing of single, time series, gated, list mode, whole body and SPECT images. The program was evaluated on a network of 10 computers at two medical centers over a 12 month period. The Macintosh H-based system performed as well as most dedicated nuclear medicine computers with respect to reliability, resolution of images, speed of data acquisition, and clinical processing capabilities. Their much lower cost, greater ease-of-use and full compatibility with standard image display, hardcopy, networking, and telecommunication formats indicate that personal computers will soon replace dedicated computers in routine practice.

VALIDATION OF A SIMPLE METHOD FOR THE SUPERIMPOSITION OF CT AND IMMUNOSCINTIGRAPHIC SPECT IMAGES IN PATIENTS WITH COLORECTAL CANCER.

MEASURED PERFORMANCE PARAMETERS Reliability: 3 of 5500 studies lost through system error Image resolution: Up to 1024 x 1024 pixels with non-linearity < 2% Data acquisition speed: 200,000 cps @ > 95% efficiency Simultaneous acquisition and processing: @ 50,000 cps Time - activity curve generation: 500 frames in 2 seconds Filtering: spatial & temporal smooth, 16 frames, 3 seconds Phase analysis: 16 frames, 100 x 100 pixels, 2 seconds List mode processing: Forward-backward framing in real time SPECT processing: 64 pixels x 64 frames @ 4 slices per second

Collimation, angular sampling and pixel size are acquisition parameters affecting partial volume effect and resolution which should respectivly be minimized and optimized for a better quantification of SPECT images. The influences of pixel size and angular sampling were assessed in experiments with an active line source (within a 30 cm diameter water filled cylinder) and with a Hoffman phantom filled with 123-I. A Sophycamera DSX equipped with a low energy high resolution collimator (6.5mm at 10cm) was used. Low count rate acquisitions of same total duration were performed in 64x64 matrix with 3 zoom factors (pixel size of 9.1, 6.3 and 4.7mm) and a sampling of 64 or 128 projections over 360°.The LSF measurement results are: Pixel size 9.1mm LSF (FWHM) 64 Proj. 18.4mm

+

128 Proj.

6.3mm

4.7ram

--- 15.9mm

* 14.3ram

15.6mm

13.9mm

18.4mm

For the Hoffman phantom acquisitions the average counts/pixel x projection were 15 for the 9.1rnm pixel, 9 for the 6.3ram pixel (a 40% decrease) and 6 for the 4.7ram pixel (a 60% decrease). The acquisition data were reconstructed using a Hamming/Hann filter. In agreement with the LSF measurements, the reconstructed Hoffman SPECT images show a dramatic improvement of image-quality when a smaller pixel size was selected, although the count rate per pixel per projection was lower. On the contrary, the 128 angular sampling did not produce any significant change of image quality for the same pixel size. Conclusion: In spite of a decrease of the count rate per pixel, these results clearly indicate that a smaller pixel size must be favored to a better angular sampling in quantitative brain SPECT.

Liehn, A. Loboguerrero

and C. Perault.

Institut Jean Godinot. REIMS (r4seau de Recherche Clinique).

FRANCE

and

INSERM

A simple method for the superimposition of CT immunoscintigraphic SPECT images is validated.

and

Ten patients are selected as follows : Clinical suspicion of colorectal cancer recurrence, abnormal but not specific CT lesion in the pelvis, positive in~unoscintigraphic SPECT study performed with antiCEA MoAb labelled with i00 MBq of i i i In. Immunoscintigraphy and 99m Tc HMDP Bone SPECT are recorded simultaneously. CT films are digitalized by a CCD videocamera connected via a PC to a SUN based Nuclear Medicine system. Three dimensional translation and scaling as well as rotation are performed. The parameters of the geometric transformation are estimated by minimizing the distance between the coordinates of typical points chosen by an operator on both CT and bone SPECT images. The superimposed frames are displayed in a grey-red bicolor scale. In all patients, the quality of the geometric registration, assessed on the superimposed CT-Bone SPECT images was good. The hot spots on eases to immunoscintigraphy corresponded in all an abnormal mass in CT. Our method has been validated and it may be used prospectively to associate the anatomical information of CT with immunoscintigraphy.

663

Wednesday, 4 September 1991

PO-4R1-21 G. Lucianani. K. Schmidt, R.M. Moresco, G. Rizzo, M.C. Gilardi, C. Messa, F. Colombo, L. Sokoloff, F. Fazio. ITBACNR, University of Milan, Institute H San Raffaele, Milan, Italy and LCM-NIMH, Bethesda, MD, USA.

HOMOGENEOUS VS HETEROGENEOUS TISSUE KINETIC MODELS FOR MEASURING rCMRglc WITH PET AND FDG. Homogeneous tissue kinetic models of the FDG method, either with or without a term for product loss (4K and 3K models, respectively) were compared to a heterogeneous tissue model in 60 min PET/FDG dynamic studies of 3 normal subjects. Rate constants were estimated from the cerebral and arterial time courses of total radioactivity for individual ROIs and whole image planes according to each of the models. The goodness-of-fit and the rates of glucose consumption (rCMRglc) for each model were examined. The results were as follows: a) the goodness-of-fit of the heterogeneity model was similar to that of the 4K model, both in individual ROIs and whole planes; it was statistically significantly better than that of the 3K model in all the planes examined and in 32% of the ROIs; b) average rCMRglc calculated with either the 3K or heterogeneity model for the whole planes was 34 p.mol/100g/min, consistent with whole brain glucose utilization values obtained with the KetySchmidt technique, whereas with the 4K model values of rCMRglc averaged 40 limol/100g/min. These results indicate that: a) the finding of a significant k4* may not be due to loss of product, but to the use of a homogeneous model for a heterogeneous tissue; b) the use of a 4K model may cause an overestimation of rCMRglc.

PO-4R1-22 M. LOBECK*, W. M~LLER-SCBAUENBURG, U. FEINE Abteilung Nuklearmedizin und spezielle Biophysik, Medizinische Hochschule Hannover* und Abteilung Nuklearmedizin, Radiol. Universit~tsklinik T~bingen THE INFLUENCE OF BACKGROUND CORRECTION AND ROI DEFINITION ON THE ESTIMATION OF LVEF For LVEF-calculation we compared the established method B (Bonn) with background subtraction based on a manually drawn ROI with a new procedure L according to LUIG. L omits a background correction and supports its findings on an automatic edge detection related to the isocount level 5/8 to the maximum cell count within the end diastolic ventricle. Based on the 'concept of area change fraction' developed by LUIG, the geometric functionality of both algorithms can be analysed. The close correlation of the LVEF with the end diastolic to end systolic change in the projected ventricular area can be ascertained for method L (r}0.99) and is included in.the direct comparison with method B. Rest and stress values of cardiovascular normal patients (N: n=16) were calculated. The mean LVEF from both methods was introduced (rest: 66!6% / stress: 69!7%). The lower limit of normal resting LVEF was defined at 58%. Within a non-selected patient group P (rest: n=43 / stress: n=33), a LVEF-correlation r=0.94 between method B (min=18% / max=94%) and method L (min=10% / max=88%) was achieved (n=76). The mean LVEF-change under stress shows a decrease for B (N:-0.3% / P:-3.1%) and an increase for L (N:+8.4% / P:+1.2%). These differences in stress response of LVEF between both methods is significant (p<0.01), caused by a systematic underestimation of background activity with method B for stress studies. It is shown as to which function the analysed procedures correlate in LVEF at different background levels for B. Background fractions below 60% of the end diastolic count density on the left ventricle are not relevant for LVEF estimation.

PO-4R1-23

PO-4R1-24

b:. [~_acbi_d_a, N. Honda, T. ['damiYa. T. Takahashi. T. Taktshima. T. Kamano. M. l~luramatsu. R. Ban. Saitama {dedtcal School, K a w a g o e . a n d S h i m a d z u C o r p . KYOtO. J a p a n .

Enn MariDuu I, J-E Westlin 2

3D DISPLAY OF T c - 9 9 m [alBl k,IYOCARDI A[, SC 1 NT i GRAId. The purpose of the sttldy is to investigate the diagnostic: ahilitY o f 31) d i s p l a y of Tc99m MIBI m y o c a r d i a l scintigram8 compared with T1-20I and Tc-99m kM B I SPECT images in patients wiLh old m~,ocardial infarction. In 16 cases T1-20I and T o - 99111 m y o c a r d i a l scintigraphy were performed within 2 weeks. There were la male and 3 female patients with mean age (SD) of 61 . 9 ( 1 5 . 7 ) years. T1201(IIOMBq) or T~-99m [dIBI {550MBq) were administered i.v, and 32 views were obtained during a lSO-degree-arc of a gamma camera f r o m RAO 4 0 - d e g r e e t o LPO 5 0 - d e g r e e po:~itions (15 sec/view for Tc-99m and 30 see/view for T1-201). Tomographic images were created by Shepp-Logan filtered backprojection without attenuation correction. 3D images were created by depth-shadi ng method from 16 viewing angles. Two p h y s i c i a n s bl fnded -to clinical i nformat ions interpreted SPECT images and 3D images by consensus on s e p a r a t e o c c a s i o n s . Among 41 fixed d e f e c t s o n Tl-201 S P E C T (n=I6). 40 d e f e c t s w e r e found in b o t h T c - 9 9 m SPECT a n d 3D i m a g e s . Sensitivity and specificity of T1-201 SPECT, Tc-99m SPECT. and 3D i m a g e s were equal (78.9 and 91.3% , respectivelY, n=6). However, the observers reported that 3D images were easi er than tomographi c s I ice images to diagnose defects. Ue conclude that 3D i m a g e s ,lay be u s e f u l f o r d i a g n o s i n g defects of left ventricles.

664

perfusion

iDep of Hosp. Physics, Uppsala, SWEDEN.

2Dep of Oncology Univ. Hospital,

ECTOMC~RAPHY - A TOMOGRAPHIC SLANT HOLE COLLIMATOR

TECHNIQUE USING A ROTATING

Ectomography is a tomographic technique where a slant hole collimator is attached to a stationary gamma camera. Projection images are acquired during a stepwise rotation of only the collimator about an axis perpendicular to the collimator face. Hence, the gamma camera detector can be positioned close to the organ of interest. In comparison with SPECT, this results in a more advantageous imaging geometry for superficial organs. Whereas SPECT is better for studying organs occupying large volumes, such as the liver and the lungs, ectomography should be preferable when studying organs such as the hip joint, the thyroid and the facial bones. A rotating slant hole collimator forms a conical reconstruction volume, the size of which depends on the slant angle o f the collimator and the gamma camera field of view. The reconstruction volume is the volume of the object intersected by all projections; the volume outside is''only partially viewed and details there are imaged with less resolution and contrast. The cone has its base area at the collimator face and its top within the object. The reconstruction consists of high-pass filtration and bilinear interpolation during back-projection. Each reconstructed slice will have a thickness of about 0.6 cm similar to a conventional SPECT slice thickness, when the acquisition matrix is 6 4 x 6 4 . Ectomography has, at our hospital, been used mainly for detecting metastasis in the skeleton. Some examples will be demonstrated. Ectomography seems superior detailed information about uptake.

to SPECT superficial

in detecting radionuclide

Wednesday, 4 September 1991

PO-4R1-26

PO-4R1-25

O.Muzik~ R.Beanlands, K.Lee, M.Mintun, T.Mangner, J.Moskwa, G.Hutchins, K.Allman, N.Petry, N.Nguyen, M. Schwaiger University of Michigan, Ann Arbor, MI

J. MAS, R. BEN YOUNES, A. POUSSE, P . H A N N E Q U I N * , R. B I D E T B i o p h y s i c s & N u c l e a r M e d i c i n e Lab., 25000 B e s a n g o n and *CIN, 74000 A N N E C Y - F R A N C E N E W R E S U L T S ZN C O M P T O N S C A T T E R C O R R E C T I O N OF N U C L E A R I M A G I N G BY S P E C T R A L C O N S T R A I N E D F A C T O R A N A L Y S I S (SCFA) In o r d e r to c o r r e c t for C o m p t o n scatter, we have recently developed a new recombination m e t h o d b a s e d on F a c t o r A n a l y s i s (FA) u s i n g a s p e c t r a l c o n s t r a i n t . The e f f e c t i v e n e s s of the S C F A a l g o r i t h m h a d b e e n d e m o n s t r a t e d on M O N T E CARLO s i m u l a t i o n s and real phantoms. The p r e s e n t w o r k deals w i t h f u n d a m e n t a l q u e s tions o p e n e d by this n e w approach, a n d we h a v e extensively s t u d i e d the e v o l u t i o n of t h e results u n d e r a wide range of p a r a m e t e r s . First, it is of p r i m e i m p o r t a n c e to d e f i n e t h e b e s t n u m b e r of e n e r g y w i n d o w s w i t h i n b o t h C o m p t o n and P h o t o p e a k e n e r g y ranges. C o m p a r i s o n of results o b t a i n e d for e i t h e r the c l a s s i c a l p h o t o p e a k w i n d o w (±10%) or s a m p l e d p h o t o p e a k w i n d o w associated w i t h c o n s t a n t C o m p t o n e n e r g y sampling, are p r e s e n t e d . Secondly, the a l t e r a t i o n of t h e F A e x t r a c t e d f a c t o r s vs. t h e ROI s i z e was i n v e s t i g a t e d . Thirdly, the r e a l p o t e n t i a lity of the m u l t i d i m e n s i o n a l a n a l y s i s is s t u d i e d b y c o m p a r i n g the s c a t t e r c o r r e c t e d images o b t a i n e d w i t h the F A e x t r a c t e d f a c t o r a n d w i t h v a r i o u s ROI s p e c t r a l curves. F i n a l l y , as far as the o b s e r v e d s c a t t e r is a c o m b i n a t i o n of m a n y C o m p t o n s c a t t e r orders, r e s u l t s o b t a i n e d w i t h s e v e r a l F A e x t r a c t e d C o m p t o n f a c t o r s are presented. This extensive study more precisely demonst r a t e s t h e limits and the real e f f i c i e n c y of the S C F A method.

I N V E S T I G A T I O N OF M Y O C A R D I A L PERFUSION USING DYNAMIC PET AND GENERATOR PRODUCED COPPER-62 PTSM Copper-62 PTSM (CP) is a new lipophilic positron emitting perfusion tracer which has prolonged tissue retention. We studied the myocardial kinetics of this tracer in 4 dogs at variable flow states and in 2 patients with CAD at baseline and after adenosine (0.14 mg/kg/min for 6 rain). In 2 dogs, serial intracoronary injections of CP ( 200-500 uCi) yielded biexponential tracer clearance with a high initial extraction measured using a NaI probe. The half-time (tv2) of the rapid early phase was 20.1 + 1.4 sec, while the tl/2 of the slow phase was 109 + 6 rain. The retention fraction of the slow phase averaged 68.7 + 2.1% over a flow range of 1.2 to 3.I ml/min/g. Serial dynamic PET imaging was performed on 2 dogs with arterial sampling for arterial input function. CP myocardial retention showed a 2.2 fold increase while flow determined by microspheres increased by 6.1 fold indicating underestimation of myocardial blood flow at high flow states. In patients the PET images were of good quality with rapid tracer clearance from blood. At baseline and during adenosine, heart to lung ratios were 10.0 and 10.3, while m y o c a r d i u m to blood pool ratios were 2.2 and 3.5 respectively. D y n a m i c PET imaging showed a 2.1 fold rise in absolute CP retention from 0.28 at baseline to 0.59 after adenosine in the normal region, while the ischemic territory showed no change with a retention of 0.25 before and after adenosine. Thus copper-62 PTSM represents a suitable new PET tracer for the qualitative evaluation of regional blood flow in the human heart. Quantification of blood flow by copper-62 PTSM appears to be limited by the decreasing retention fraction at high flow states and requires further study using tracer kinetic modeling.

PO-4R1-27

PO-4R1-28

L. Nyitrai, L . E . F e i n e n d e g e n , H. Herzog, E.Rota Kops

L. Nyitrai, H. Herzog, K. Ziemons and L.E. F e i n e n d e g e n I n s t i t u t e of Medicine, R e s e a r c h C e n t r e Jfilich, P.O.Box 1930, D - 5 1 7 0 Jiilich, FRG

I n s t i t u t e of Medicine, R e s e a r c h 1930, D - 5 1 7 0 Jtilich, FRG

Centre

Jtilich,

P,O.Box

THE IMPORTANCE OF THE FIRST-PASS BRAIN PERFUSION ( F - P BP) FART IN THE EVALUATION OF THE TRANSPORT RATE CONSTANT (k2) IN nC-METHYL-D-GLUCOSE (CMG) POSITRON EMISSION TOMOGRAPHY (PET) BRAIN STUDIES. Our s i m u l a t i o n s t u d i e s were d i r e c t e d to i n v e s t i g a t e t h e i m p o r t a n c e of a f a s t p l a s m a and b r a i n time a c t i v i t y c u r v e (TAC) s a m p l i n g p r o c e d u r e for a n a l y s i n g t h e r a t e c o n s t a n t k2 of c e r e b r a l glucose t r a n s p o r t . The e x a c t d e t e r m i n a t i o n of kz is i m p o r t a n t , as t h e s u p p l y for t h e cerebral energy demand is dependent on glucose transport. In s i m u l a t i o n s t u d i e s F-P BP TACs were r e s t o r e d a c c o r d i n g to t h e e x p e c t e d noise l e v e l in CMG PET s t u d i e s and its accuracy was compared with the e x p e c t e d e r r o r a s s o c i a t e d w i t h t h e u n d e r s a m p t i n g , The f i r s t 60 s e c o n d s in t h e p l a s m a TAC were s i m u l a t e d with two F - P BP TACs o b t a i n e d from f a s t s e q u e n t i a l g a m m a c a m e r a s t u d i e s ( t h e m a x i m u m a m p l i t u d e d i f f e r e n c e was 40%). T h e n t i s s u e TACs (TACt) were c a l c u l a t e d for e a c h p l a s m a c u r v e u s i n g a two c o m p a r t m e n t a l model. When k2 (in rain -1) was v a r i e d from 0.05 to 0.3 by s t e p s of 0.05, TACt was c h a n g e d by 3,64_+0.07% a t 1.5 rain and 1 3 . 4 8 / 0 . 8 2 % a t 6.25 rain. At a f i x e d k2 of 0.2, the two p l a s m a TACs g a v e t h e r e l a t i v e d i f f e r e n c e s of 8,8%, 1.7%, 0.8%, 0.3% b e t w e e n t h e two TACts a t 1.5, 6.25, 10.0, 15.0 min, r e s p e c t i v e l y . The F - P BP and t h e p l a s m a TACs could be r e s t o r e d with less t h e n 10% r e l a t i v e e r r o r i n s t e a d of t h e e x p e c t e d e r r o r of 40% with sampling at 6-15 s intervals. T h e s e r e s u l t s show, t h a t s a m p l i n g a t 1 s i n t e r v a l s for a t l e a s t 1 min is n e c e s s a r y to o b t a i n s a t i s f a c t o r y b r a i n and p l a s m a TACs to a c h i e v e a kz a c c u r a c y of 20%. This approach is also useful in s e l e c t i n g the optimal n u m e r i c a l c o m p u t a t i o n a l m e t h o d for o b t a i n i n g kz v a l u e s in CMG d y n a m i c PET s t u d i e s .

NOISE QUANTIFICATION AND REDUCTION IN DYNAMIC POSITRON EMISSION TOMOGRAPHY (PET) STUDIES. This work was d e s i g n e d to i n v e s t i g a t e t h e noise l e v e l of time a c t i v i t y c u r v e s (TACs) o b t a i n e d from f a s t d y n a m i c PET s t u d i e s as a f u n c t i o n of a lumped p a r a m e t e r (LP) which i n c l u d e s a c t i v i t y c o n c e n t r a t i o n (A), size of t h e r e g i o n of i n t e r e s t (SROI), time r e s o l u t i o n (RT), and of t h e m e t h o d of r e c o n s t r u c t i o n . In a d d i t i o n t h e r e l a t i v e d e c r e a s e of noise due to a l o w - p a s s f i l t e r i n g was studied. A h o m o g e n o u s c y l i n d r i c a l p h a n t o m filled with F - 1 8 a c t i v i t y was s c a n n e d with a PET c a m e r a SCANDITRONIX PC 4096 15-WB. D a t a were a c q u i r e d in list mode and s o r t e d a t d i f f e r e n t time i n t e r v a l s from 1 to 64 s. A f t e r t h e s o r t i n g p r o c e d u r e s two d i f f e r e n t r e c o n s t r u c t i o n a l g o r i t h m s , a f i l t e r e d b a c k p r o j e c t i o n (FB) a n d an i t e r a t i v e r e c o n s t r u c t i o n (IT), were applied, In both c a s e s t r a n s mission s c a n s w e r e used to o b t a i n a t t e n u a t i o n c o r r e c tions. The TACs were g e n e r a t e d u s i n g ROIs with 1 7 5 2585 pixels. T h e n a " l o o k - u p " t a b l e of t h e e x p e c t e d r e l a t i v e noise (N) was o b t a i n e d for d i f f e r e n t RT and SROI. T h e applied c u t - o f f f r e q u e n c i e s (fc) of a l o w - p a s s f i l t e r was in t h e r a n g e of 0.00S-0.15Hz. The r e s u l t s c l e a r l y show t h e n o n l i n e a r b e h a v i o r of N as f u n c t i o n of SROI. N is r e d u c e d by a f a c t o r of a b o u t 9 when t h e SROI is i n c r e a s e d 15 times. The l o w - p a s s f i l t e r with fc=0.15 Hz r e d u c e s N by t h e same f a c t o r as would be a c h i e v e d by 3.7 t i m e s l a r g e r SROI or 6 t i m e s l a r g e r RT w i t h o u t c h a n g i n g t h e f r e q u e n c y c h a r a c t e r e s t i c s of a f i r s t - p a s s b r a i n c i r c u l a t i o n signal. Below an N of 10% t h e r e is only 1% a b s o l u t e d i f f e r e n c e of N when u s i n g e i t h e r IT or FB. However, if N is 12% for IT, one f i n d s it to be 21% for FB. The o b t a i n e d r e s u l t s help in p l a n n i n g PET s t u d i e s , i.e. how much a c t i v i t y m u s t be i n j e c t e d and w h a t SROI should be u s e d f o r TAC g e n e r a t i o n to g e t t h e e s t i m a t e d p a r a m e t e r s a t t h e g i v e n a c c u r a c y . The e x p e r i e n c e of such a p r o c e d u r e also allows d i s t i n c t i o n b e t w e e n e f f e c t s due to t h e m e a s u r e m e n t s y s t e m , including d a t a p r o c e s sing, and t h e p h y s i o l o g i c a l e f f e c t s to be examined.

665

Wednesday, 4 September 1991

PO-4R1-29

PO-4R1-30

Y.Peteanief,F.Aubry,B.Aubert U66 INSERM, Institut GUSTAVE-ROUSSY, FRANCE

'~ PILLOy

- DEPT.

NUCLEAR

MEDICINE

- MEDUNSA

RSA

94805 VILLEJUIF -

IMPROVEMENT IN Q U A N T I T A T I V E BY WIENER FILTERING.

R P CLAUSS

SPECT

Quantitation in SPECT is mainly affected by spatial resolution of imaging system and statistical noise. AS Wiener Filters (WF) were designed to restore spatial resolution while decreasing noise level, we investigated improvements in quantitative performances of SPECT by Wiener filtering with respect to conventional filtering used in Filtered Back-Projection (FBP). In order to estimate the parameters of WF : Modulation Transfer Function (MTF), 0bjet Power Spectrum (OPS) and Noise Power Spectrum (NPS), we (i) modeled the MTF by a Gaussian function, (ii) established classes of images having similar OPS based on Gaussian distributions and (iii) considered the NPS to be constant for projections. A Monte Carlo (MC) code was used to simulate hot spheres of Tc-99m in a radioactive background for conventional imaging conditions : Low Energy High R e s o l u t i o n collimator (i0 nun FWHM at 15 cm) and a 126-154 keV energy window. Special attention was paid to small sized lesions (2 to 5 cm) and low object to background contrast (2 to 8). Image contrast was compared with conventional FBP reconstruction using Hanning and Butterworth filters. Restored images by WF showed good noise suppression and improvement in image contrast and resolution. Small lesions (under 3cm) fully benefited from WF. Assumption of shift-invariance of the MTF which is performed in linear filtering will be discussed based on collimators design and scattering geometry. Extension of WF to 1-131 SPECT imaging is underway for the clinical use of SPECT in d o s i m e t r y during evaluation of new metabolic radiotherapy techniques such as radioilmrnunotherapy.

- DEPT.

NUCLEAR

DETERMINATION OF LUNG MEDICINE TECHNIQUES

MEDICINE

VOLUMES

- MEDUNSA

BY N U C L E A R

AI~ The aim of t h e s t u d y wee to e s t a b l i s h t h e a c c u r a c y of a m e t h o d d e s i g n e d to d e t e r m i n e r e g i o n a l lung volumes and I l o w s by N u c l e a r M e d i c i n e T e c h n i q u e s using 138 Xe.

METHOD 26 C o n s e n t i n g p a t i e n t s took p a r t in t h e s t u d y . 8 0 0 MBq el 133 Xe was i n j e c t e d i n t o a r e b r e a t h i l l g c i r c u i t s p i r o meter. The a c q u i s i t i o n was done in two p h a s e s : a p o s t e r i o r d y n a m i c a c q u i s i t i o n of 4 0 0 f r a m e s o * 0 . 1 6 s e c o n d eaQh tot t h e d e t e r m i n a t i o n e l s p i r o m e t r i c lung volumes, and a n o t h e r a c q u i s i t i o n e l 5 0 f r a m e s of 1 s e c o n d d u r i n g t h e w a s h o u t of Xbnon, T h e 4 0 0 f r a m e s d y n a m i c a c q u i s i t i o r l r e c o r d e d t h r e e c y c l e s of T i d a l b r e a t h i n g and t h r e e m a x i m u m i n s p i r a t i o n and e x p i r a t i o n m a n o e u v r e s . ( A f t e r h o m o g e n o u s m i x i n g of Xenon in t h e lungs and b e f o r e s i g n i f i c a n t d i f f u s i o n i n t o t h e b l o o d ) . T h e c o n v e r s i o n f r o m c o u n t s to m i l l i l i t r e s was d o n e by r e l a t i n g t h e d i f f e r e n c e In c o u n t s over b o t h lungs to t h e d i f f e r e n c e in volume d u r i n g t h e f i r s t m a x i m u m inspiration - expiration manoeuvre. The s t a n d a r d s p i r e m e t r i c volumes of b o t h l u n g s w e r e t h e n c a l c u l a t e d I t e m b o t h time-activity and a p i r o m e t r i c curves and c o m p a r e d . R e g i o n a l lung a i r volumes and I l o w s w e r e t h e n c a l c u l a t e d over s e g m e n t s of t h e lungs and t h e p a t t e r n of w a s h o u t was i n v e s t i g a t e d on l u n c t l o n a l i m a g e s . RESULTS T h e s e s p i r o m e t r i ¢ p a r a m e t e r s w e r e g e n e r a t e d on p r e n e u m e c t o m y , a s t h m a , p u l m o n a r y e m b o l i s m and t u b e r c u l o s i s p a t i e n t s and showed c l i n i c a l l y m e a n i n g f u l c h a n g e s . s p e v i f ! e e x a m p l e s are p r e s e n t e d

CONCLUSION T h i s m e t h o d is u s e f u l b e c a u s e i t is t h e o n l y one to reliably elucidate regional ventllatory pathology.

PO-4R1-31

PO-4R1-32

JM. R O C C H I S A N I * * , R.BEN YOUNES*, JY.DEVAUX**, R.BIDET* * L a b o r a t o i r e de B i o p h y s i q u e , B e s a n g o n , F r a n c e ** C H U C o c h i n , P a r i s , F r a n c e

R.Ropolo*,P.Cesana*,G.Picciotto, A.Sargiotto, M.Camp-~a, M.Baccega, P.G.De F i l i p p i * H e a l t h P h y s i c s Dep. - O s p . Molinette,Torino N u c l . Hed. D e p . - O s p . H o l i n e t t e , Torino,Italy

REMOTE

STUDY OF URETERAL PERISTALSIS FOURIER TRANSFORMS ( F F T ) .

SHARING

OF N U C L E A R

MEDICINE

D A T A BY ISDN

NUMERIS is t h e recently available french public Integrated Services Digital Network which offers a fully secure transmissions of d a t a at t h e rate of 6 4 0 0 0 b i t s p e r s e c o n d for a p r i c e less t h a n t w i c e a t e l e p h o n e call. We h a v e u s e d t h i s n e t w o r k to interconnect t h r o u g h o u t M a c i n t o s h c o m p u t e r s as g a t e w a y s t w o local area networks (LAN) o v e r 500 Km. F u l l y t r a n s p a r e n t s h a r i n g of d a t a b y b o t h s i t e s w e r e so r e a l i z e d b e t w e e n a M a c i n t o s h b a s e d L A N a n d an heterogeneous Ethernet based Nuclear M e d i c i n e L A N (ADAC Lab.) c o n s i s t i n g in s e v e r a l dedicated systems and personnal computers. This a l l o w e d to s e e k a d v i c e f r o m a d i s t a n t e x p e r t by supplying him with all clinical informations, biological data and images of various modalities (NMR, body scan, ...) . R e m o t e archiving and report editing were also performed. A 512x512 pixels, 256 graylevels i m a g e was t r a n s m i t t e d in l e s s t h a n one m i n u t e . Numeris offers other advantages upon classical telephone l i n k s as s i m u l t a n e o u s and b i d i r e c t i o n n a l t r a n s m i s s i o n of v o i c e , text, and images that could be conveniently used for communication between institutions.

666

WITH

FAST

Ureteral byperperistalsis (UHP) i s known t o be an e a r l y symptom o f u r e t e r a l obstruction and its detection may b e a u s e f u l t o o l for s u r g e r y and f o l l o w - u p o f t h e p a t i e n t . [t is possible to study noninvasively ureteral peristalsis (UP) w i t h a m e t h o d w h i c h d i s p l a y s s i n g l e UP w a v e s i n a t i m e - s p a c e m a t r i x from a renal scintigraphy typically performed with an a c q u i s i t i o n o f 4 8 0 f r a m e s o f 2 . 5 s e c . Such visualization is intrinsically blurred especially above 4-5 waves per minutes. Ne attempted to analyse the curves generated f r o m ROIs on ~ h e u r e t e r s w i t h the FFT m e t h o d s t o d e t e r m i n e p o w e r spectrum. In fact the " p o w e r spectrum allows to detect f r e q u e n c i e s u p to the Nyquist frequency given by I / 2 t w b e r e ' t is the sampling period (i.e. 12 waves/min for the typical acquisition). The metbod was tested by means of a simulatioo of UP obtained with ten sources equally spaced on a rigid support that could move at a constant velocity under the gamma camera. A flood source was placed under the mobile phantom in order to simulate background. The velocity of the sources train was varied up to 12 waves per minute. The test performed was successful for frequencies less than 11 waves/min. This method applied to 25 patients injected with 9 9 m T c - M A G 3 results able to determine peristaltic f r e q u e n c y in many pathologies including UHP.

Wednesday,

PO-4R1-33 J. Ruckgaber, F .Bitter, P. Schmidlin 1, U. J~iger2, W.E. Adam Universit/it Ulm, Nuklearmedizin, 1DKFZ Heidelberg, 2Radiologische Klinik Stuttgart

4 September

1991

PO-4R1-34 5, Savolainen, K. Liewendahl Deporlment of Physics, Universi.(yof Helsinki and Depadment of Clinical Chemistry, Division of Nuclear Medicine, Helsinki University Cen.(raJ Hospital

ITERATIVE SPECT RECONSTRUCTION Based on the 'optimized geometric mean algorithm' from Schmidlin (1972) which was used for Positron Emission Tomography (PET) an Iterative SPECT Reconstruction (ISR) was developped. The original algorithm was adapted to the special demands of SPECT (Point Spread Funktion, flood- and center of rotation correction), lndependet of the matrix-size, 180° or 360 ° studies are reconstructed within the same processing time. The attenuation-correction can be performed during the reconstruction process (exept for myocardial studies). To reduce the considerable computing time a FlashISR was devlopped with the same properties as ISR but 6 times faster. Table 1 gives the time for several computers in seconds and table 2 compares quantitatively some SPECT parameters of ISR (11 iterations) and FBP (Butterworth n=5, c=0.4). Table 1 ISR FISR Table 2 1SR FBP VAX 8530 40 7 resolution in mm 15.3 23.1 MicroVAX 3100 70 12 contrast* in % 65.1 52.8 MicroVAX 11 176 30 diameter deviation* 51.0 139.0 (FBP 3) * 10 mm rod Additional advantages of the ISR algorithm are: no star artifacts no filter required good-quality slices also for relative bad-quality projection data We conclude that FISR is feasable also for routine work with acceptable processing times and without the needs for optimizing the applied filter. The properties of FISR are superior in comparison to FBP.

PO-4R1-35 I. Sj'~qren, G. B l o m a v i s t Departments of Psychiatry Clinical Neurophysiology, 1 0 4 01 S t o c k h o l m , Sweden VALIDATZON OF MATHEMATICAL RECEPTOR BINDING PARAMETERS

USE OF SINGULARVALUE DECOMPOSITIONFOR INTERPRETATIONOF GAMMA IMAGES In this work singular value decomposition (SVD) method is presen~{ed as a general Wol for analysing gamma images. The analysis of the images can be reduced to the question: what is .(he up.(ake of '(he organ in question vs. the blood background. Maihema.(ically: is i.( possible to find the basis vedors for ~he sign< which differs from the background? SVD can be used to find an or.(honormal basis for the image maW< and thus enables separation of the "real" signal from noise. SVD makes i{ possible [o calcula.(e the signal W noise ratio in an objedive way, because ~he calculation is not dependen.( on the choice of the regions of inWresL The usefulness of the SVD has been demons.(ra.(ed in subtradion of the isotopic images of differen~ isotopes. SVD can be also used in the quanfiWtive analysis of the brain sWdies; one has to compare the singular vales of the left and right side of the brain images with each other. Also the spleen-liver ratio ealculaWd with highest singular values of SVD was found to correlale wi~h .(he ratio calculaWd using the region of interest division method (r:0.85, p
PO-4R1-36 and Psychology, Karolinska Institute,

ALGORITHMS FOR OBTAINING IN PET STUDIES .

We have tested different mathematical algorithms for determination of the receptor ligand parameters Brnax, KD, kon and kof f in a standard cor~partment model for radioligands in the brain with one tissue compartment for free radioligand (CF) and one for specifically bound (CB). The amount of free radioligand was considered known by using a reference region. Simlllated data with and without statistical fluctuations were generated from given binding parameters and different specific activities. We have also considered different mixtures of tissue with specific binding and tissue without specific bindlng. The first method is to use the differential equation describing the concentration of specifically bound radio ligand directly to make linear fits of Bmax, K D and kon and then obtain kof f = kon.K D (Slomqvist et al 1989). The next approach is to solve the differential equation for CB analytically in terms of the known CF and make a fit to measured data An a traditional least squares manner. We have also tried a nur~erical solution of the differential equation. The linear method is fast and works extremely well for data with no statistical fluctuations in a homogeneous region. The analytical solution is of course slower but on the other hand far more reliable for randomized data and in regions which are inhomogeneous. The ntlmerical solution gives approximately the same result as the analytical solution but is even slower. Brain maps of the parameters are readily obtained with the linear method but can also be constructed using the analytical solution. However the numerical solution is too slow to be used pixel by pixel. References

BLomqvist G, Pauli S, Farde L, Eriksson L, Persson A, Salldin C, Maps of receptor binding pararr~ters in the human brain - a kinetic analysis of PET measuremensts. Eur J of Nucl Med 16:257-265 (1990) .

Z. S z a b o , L.H. Monsein, Y. M a r u k i , P.J. Jeffery, B.B. van Heerden, G. D e b r u n , S Sostre, C. S e k i , T.K. Natarajan, H.N. Wagner Jr., E.E. Camargo. The Johns Hopkins Medical Institutions, Baltimore, U.S.A. QUANTITATIVE

IMAGING

OF

CBF

WITH

TC-99m-HMPAO

Quantitative imaging of regional cerebral blood flow ( C B F ) in M K S u n i t s with a technetium-99m labeled compoun~ would be an important tool for diagnosis and follow-up of patients with cerebrovascular diseases. The goal of this study was to develop a technique for quantitative measurement of CBF with Tc-99m-HMPAO. The microsphere model was used for calculation of CBF. The cerebral activity was corrected for the retained fraction using impulse response function analysis of the brain time-activity curve. Octanol extracted arterial activity served as input function. Experiments were performed in f o u r d o g s . In two animals the cerebral blood flow was left unaltered. In one animal CBF of the right hemisphere was reduced by injection of latex spheres into the right middle cerebral artery. Finally, in t h e f o u r t h animal CBF was increased by hypercapnia. In 6 h u m a n subjects, absolute brain radioactivity was measured by high resolution SPECT to calculate CBF. The CBF values obtained with this technique in t h e a n i m a l s correlated well with the reference microsphere method (r=0.86-0.97). The human measurements resulted in a v e r a g e CBF values ranging from 38 to 48 ml/min/100 g. Our preliminary data demonstrate that calculation of be feasible

regional CBF and deserves

with Tc-99m-HMPAO may further validation.

667

Wednesday, 4 September 1991

PO-4R1-37

PO-4R1-38

A. Teresi~sk~,E. 5oaiews~a, B. Szusilak, S, Konieczna Instituteof Cardioiogy,Warsaw,Poland

J.A. Thie, K.F. Hubner, and G.T. Smith. University of Tennessee Medical Center, Knoxville, TN.

LIMITED ACCURACY OF BACKGROUNO INKS) SUBTRACTION ALGORITHflS IN CARDIAC PERFUSION STUDIES: THE INFLUENCE OH RESULTS OF CLINICAL STUDIES ~iTH Tc-99m-MIBI (CARDIOLITE)ANDTI-201 Proper BK6 subtractionis crucial to the successof quantitstiveplanar perfusion imaging,For CAROIOLITEand TI-20I images,the modified interpolative BKG evaluationmethod {NetMod)has been proposed (Sinusas~et a1,1989). PURPOSE: To assessthe inFlueuceof MetHodon resultso~ clinicalstudies eith CARDIOLITEend TI-201. METHOD: Stress-rest CARDIOLITEand stress-redistributionTI-201 studieshere analyzed: II qualitativelyNithout BKG subtraction(COMPI);21 attar applying MetHod (COMP2).255 segmentsin 17 male eith CAD mere assessed by 3 independent observers - for perfusionde~ect reversibilityor persistence, RESULTS: 11 The segment" to segment concordancewas: in COMPI - 74 % , in COMA2 - 76 ~ ; the diRferencewas not significant;21 HetNod failed to correct properly For e~tracardiac activities significantly overlapping the heart, DISCUSSION:Full concordancebetween CARDIOLITEand TI-201studiesshould not be expected becauseof the diPFerences in energy and kineticsoR these agents. Homever,clinical materialsupports the conclusionsdramn True computer sieulati0ns and phantomimages ITeresiAska,1991)that better concordance ought to be achievable iT an algorithm can be Roundthat improveson the MetHod.

Sinosas M, Beller GA,Beit~, WH,Vlnsuo EL,Brookeean V,J~atsunDB, Quantitative Planar laagin 9 .ith Technetiue-99aMetho.~yisobutyl lsonitrile: Comparisono{ Uptake Patterns .lth ThaHiut-2Ol. JNuclHed~O:145b-1467J¢lgBgl Teresidaka ~, Background evaluation in quantitative i=aging .ith Tc-qgeRIB;(CARBIOLITE) and TI-201: how much have we approached an accurate, universal algorithm? 2rid International SymposJua on Cunputer Applications in Noclear Medicine and Cardiac Magnetic ResonanceImaging, Rotterdam, March20-

22, 1991

APPLICATION OF NON-INVASIVE PARAMETER IDENTIFICATI(~q TO PET AMINO ACID BRAIN TUMOR STUDIES A 2-comp~t model which includes tissue perfusion (F) and forward transport (KI) has been studied for extracting physiologic information frcm dynamic AC2~ PET brain scans without arterial blood sampling. The input function, C(t)=Aexp(-at)+(l-A)ezp(-bt), for t > t ~ e is taken from time activity Curves in the sagittal sinus. Clearance curve shapes determine A, a and b. When backdiffusion is ignored, extraction fraction E=KI/(K~+F) and kI=(KI+F)/V can be identified. Using this approach, E and k I were identified in 9 brain tzraors in 6 patients: Patient #! #2(3 lesions) #3 #4 (Ist lesion) #4(2nd lesion) #5 #6

kI

0.13 0.041 -0.031 0.087 0.022 0.139

0.58 3.8 >9.0 3.4 0.26 8.9 0.32

PO-4R1-39

PO-4R1-40 Vladimir Vidyukov. Central Institute for Education. MOSCOW , USSR

Introduction : This paper presents the method of calculation and the results obtained with a 3D animated model used for representation of the left ventricle (LV) tomoscintigrams with 201Tl This model permits also segmental quantification of perfusion. Material and methods : SPECT imaging was performed after injection of 2 mCi of thallium and data were acquired on a Siemens Rots II gamma camera. 32 projections were obtained from a 180" acquisition. Data were processed using a Siemens Maxdelta computer. The first step was the modellsation of the surface of a normal LV in 256 facets numbered from 1 to 256. For purpose of animation, 14 views at angles spaced by 12" were also calculated hi the same way and stored on disk. The second step is done for each patient. From each short axis slice, the maximum uptake is calculated along 16 radius giving thus a table of 256 values. These values are scaled to a maximum of 256 corresponding to the pixel with the maximum calculated uptake and the color table is arranged so that the color of each facet reflects its intensity. The animation of the model is provided by close loop display of the 14 views. For comparison between stress and redistribution, the LV is divided in 13 segments (1 apical, 3 anterior, 3 septal, 3 inferior and 3 lateral regions), For each segment the calculated value obtained at stress can be compared to the mean value obtained in a group of control subjects and to values obtained at redistribution in order to identify reversible defects. Results : This software has been routinely used in our department for three years on 4000 tomoscintigrams. The calculation time is about 4 ran. The interobserver correlation factor is 90 %. Conclusion : The 31) animated representation of the left ventricle is a valid alternative to bull's eye representation leading to images more comprehensible for the referring cardiologist.

668

0.076 0.155 0.153 0.107 0.022 0.195 0.044

0.15 0.042 -0.032 0.095 0.023 0.161

F/V 0.50 3.7 -3.3 0.24 8.7 0.27

where all dimensioned quantities are rain-I. To obtain F independent of V, invasive sampling or calibration of the sagittal sinus activity, C(t), is required. To reduce parameter estimation error, t ~ , l/a, and/or I/b and data averaging times should be optimized to be <= i/k I and i/Ek z. As an example, these criteria were not fully met in patient #3; cc{~Dlete identifications were not possible. The parameters E and k~ reflect ACBC physiology in t ~ o r cells and may add to the clinical ewaluation of brain tumors.

C. TOUZERY. P. MORELON, F. ANDRE, A. BERRIOLO, J.M. RIEDINGER, M. TOUBEAU, J.L PELLETIER, F. BRUNOTTE Service de M6decine NudSaire Centre G.-F. Leclere - 21034 DIJON CEDEX - FRANCE ANIMATED 3D MODEL AND QUANTIFICATION OF LEFT VENTRICLE THALLIUM TOMOSCINTIGRAMS

Ek~=KI/V E/(l-E) =KI/F

E

Post-Graduate

Medical

SYSTEM OF SCINTIGRAMS RECOGNITION. We h a v e d e v e l o p e d a s y s t e m o f a u t o m a t i c seintigrams a n a l y s i s and d i a l o g u e system: computer physician. The f o l l o w i n g s t a g e s o f w o r k have been done f o r s c i n t i g r a m s analysis: 1) c o l l e c t i o n o f d a t a b a s e , 2) c h o i c e o f s i g n e s , 3) c l a s sification of scintigrams, 4) d e v e l o p m e n t o f scheme f a r c o m p u t e r c l a s s i f i c a t i o n of scintig r a m s . T h r e e s y s t e m s o f s i g n e s a r e used f o r a u tomatic analysis of liver seintigrams: britneas histogram, a r e a s o f image c o n n e c t i o n , texture signes. The f o l l o w i n g c l a s s e s d o u l d be d i s t i n quished: 1) " h e r m ~ 2 ) " f o e a l affeetationV3)"diffuss affectation". Besides, for assessing seint i g r a m s we h a v e used t e x t u r e analysis o f zone digital image ( m i o r e s t r u c t u r a l analysis) whithin t h e b o u n d a r y of w h i c h t h e e v a l u a t i o n o f homogeneity was practicaly impossible by v i s u a l perception. This method a~owed to d e f i n e t h e structures typical of m u l t i p l e small lesions (1,5 - 2 , 5 sm) a n d ' s p e c i f i c s of h e p a t o e i r r e h o ~ s i s . T h e s c h e m e on t h e b a s i s of a u t o m a t i c and microstractural analysis m a k e s it p o s s i b l e to classify 91% of l i v e r s c i n t i g r a m s with accuracy 9 6 , 0 (this d a t a w a s o b t a i n e d by a s s e s s m e n t of 350 c a s e s ) .

Wednesday, 4 September 1991

PO-4R1-41

PO-4R1-42

R. BEUSCART, M. WARTSKI~ Y. SZYBOWICZ~ F. ARCHAMBAUD,

D.A. Weber, M. Ivanovic, C. Cabahng, D.F. Sacker, C.T.C. Wong, Brookhaven National Laboratory, Upton, NY.

R. VERGNES" * Service Central de M4decine Nuc16aire, Ntal B, Lille ** See M4deeine Nucl6aire et Biophysique, Htal Bic@tre A U T O M A T I C A N A L Y S I S A N D M E D I C A L I N T E R P R E T A T I O N OF BONE SCINTIGRAPHY A n e w e x p e r t s y s t e m for a u t o m a t i c a n a l y s i s of b o n e s c i n t i g r a p h y h a s b e e n e v a l u a t e d , in o r d e r to p r o v i d e a h e l p in i m a g e i n t e r p r e t a t i o n . MATERIAL ANDMETHOD A w h o l e b o d y b o n e s c a n w a s p e r f o r m e d on 31 a d u l t s (20 w i t h k n o w n n e o p l a s i a , ii w i t h b o n e pains) using a recti-linear camera MECASERTO coupled with microcomputer. All digitalized images were automatically analyz e d b y t h e e x p e r t s y s t e m in t h r e e s t e p s : (i) i m a g e a n a l y s i s u s i n g s e g m e n t a t i o n a n d d e t e c t i o n of c o n t o u r s ; (ii) r e c o g n i t i o n a n d s p a c e l o c a l i z a t i o n of all abnormal and normal hyperfixations, p r i n t e d out as a list; (ill)the expert system gives a final interpretat i o n i n c l u d i n g t h e d e s c r i p t i o n of a b n o r m a l h y p e r f i x a t i o n s a n d the m o s t p r o b a b l e d i a g n o s i s , t a k i n g in a c c o u n t c l i n i c a l data, n u m b e r , areas, t o p o g r a p h y a n d i n t e n s i t y l e v e l of t h e s e h y p e r f i x a t i o n s . In l a s t t w o steps, we h a v e u s e d a f i r s t - o r d e r expert system. The i n t e r p r e t a t i o n of t h e e x p e r t system was compared with the diagnosis provided by t h e N u c l e a r M e d i c i n e P h y s i c i a n s . ~ESULTS : Preliminary results show a good agreement between automatical analysis and medical interpretation concerning number and localization of h y p e r f i x a t i o n s in 20 p a t i e n t s . P a r t i c u l a r l y , there was a perfect,agreement (no f a l s e n e g a t i v e ) for all 9 n o r m a l h o n e s c i n t i g r a p h y . In ii o t h e r p a t i e n t s , some d i s c o r d a n c e s w e r e o b s e r v e d in n u m b e r a n d / o r l o c a l i z a t i o n of h y p e r f i x a t i o n s . ~ONCLUSION : This a u t o m a t i c a n a l y s i s s h o w g o o d p r e l i m i n a r y r e s u l t s a n d c o u l d he u s e d to d i f f e " rentiate normal from abnormal exams.

EXPERIMENTAL APPROACH TO ATTENUATION COEFFICIENT AND FILTER SELECTION IN BRAIN SPECT. The accurate mapping of the distribution properties of the radioactivity in reconstructed brain SPECT images requires that adequate correction for the attenuation properties of the brain and scull be made and that filter selection be based on the specific combinations of the tracer distribution, counting levels and the acquisitions spatial resolution properties. We propose that the two compartment Hoffman brain phantom filled with activity concentrations proportional to the expected gray-white matter distribution in human subjects be used as a test device for making these determinations. A SPECF study of the phantom is collected in a manner identical to that used for the brain SPECT procedure. A static image with the phantom's long axes placed parallel to the collimator should be acquired as a reference image of the activity distribution. Ratios of the counts in ROIs near the central axis and the edges of the planar image are calculated and compared with the corresponding ratios calculated from the reconstructed transverse slices. The attenuation coefficient is varied to obtain the same ratios on planar and reconstructed images. On our equipment, an attenuation coefficient of 0.12 cm -1 is required to achieve the activity ratios obtained on a planar image. This compares to an attenuation coefficient of 0.09 cm -1 to achieve a fiat profile through the reconstructed image of a cylindrical phantom 22 cm in diameter filled with a uniform distribution of 1-123. This attenuation coefficient underestimates activity in the central regions of the brainphamom. Since different acquisition parameters and hardware variables will effect the determination of the optimum recontmction parameters, it is recommended that each nuclear medicine clinic doing brain SPECT repeat this exercise.

PO-4R1-43

PO-4R1-44

L Bacciottini, A Pupi, M T R De C r i s t o f a r o Section of Nuclear Medicine, UniversLty of Firenze, F iren.ze, I t a l y

P.Kopeck~,A.R~dl,B.Kopeck~,P.Svihovcov~+,K.Bakos +

/HE BRAIN R K I E N T I O N POTENTIAL' A F T E R I N T R A V E N O U S INJECTION.

(k 3 ~ ) OF

HI'IPAO

The 'retention potential' (RP) of HIdPAO is the p r o d u c t of k9 (brain trapping rate censtal~t) ~rld~ (brain partition coefficient) of the t~acer. In acc o r d a n c e with the t h r e e - c o m p a r t m e n t model of HMPAO and assuming a total extractinn a c r o s s the (f) results: b]ood-brain barrier, brain perfusion f=(rCL-RP)/(RP-rCl), w h e r e rCl is the brain l]et re-c]ional c l e a r a n c e of HMPAO. In the c a s e that f is knowr,, RP c a n be calculat~d as: RP=(f.rCI)/(f-rCI). We d e t e r m i n e d FCI a n d f in 21 brait, str-ucture~s (ROD of ~.ach of 7 ne~l-ologJcal]y v,ormdl sub.]e,-t~. H M P A O arterial diffusible input to the brain w a s mea~iured ~ith the octano] =-apld extlactiom o f the arteriaJ radioactivity, f was m e a s u r e d Jnjectir~£! 99mEc:-microspheres i~ the left ventricle after left h e a r t catheterization. Brah~ activities w e r e d e t e r m i n e d with S PEC [ $ and crmsm- caiibrated ~ith arterial activities. 0.@ t~! ~ w a s cald~J[at ed foi" ¢ each

0.6 0.4

-

.c.- ~.~.--

0.2 0

oi.

0 r'CSF

(ml/g/mtn}

ROI.

r Cl

relationship ~,ith f w a ~, ~itteo with a fib,ear regressiom: r Ci=O.07+o.q3-f. p< 0.001. RP resulted i.[~720.05 inl/g/min (n,ean±s~m). (~ssumimg RP tO be co~,stamt, it iS po~s,illble I o calc.ulate f from rCl of

(Research supported by U.S. DOE Contract DE-ACO276CH00016. )

Nuclear Research Institute,Re{,Czechoslovakia +Institute of Biophysics,Prague,Czechoslovakia EVALUATION OF NEUTRAL DIALKOXY DITHIOPHOSPHATE COMPLEXES OF TI-201 AS MYOCARDIAL PERFUSION TRACERS Rapid redistribution of thallous ion creates difficulties in the timing of early images and causes delayed studies to suffer from poor target-to-background ratios.A myocardial perfusion agent having lower rate of myocardial activity wash-out might be an advantage. Our recent studies with 201-Tl-dialkoxy-dithiophosphates (DADTP) in animals have shown high affinity of these lipophilie chelates for myocardium. The agents are conveniently prepared by adding 201-Ti-Chloride to a weighed amount of respective ammonium DADTP salt. Ten 2OI-TIDADTP agents have been evaluated after i.v. administration in rats,all of them exhibit good or excellent myocardial uptake and retention,rapid blood clearance and low lung,spleen and liver accumulation.Representative biodistribution data for 201-Tl-diisopropyl-derivative (DIPDTP) are given below: 201TI-DIPDTP complex in rat (% dose/organ,n=5,~=8-15 min blood heart lung liver hrt/bl hrt/lung hrt/liv

%)

I 4.12 2.15 5.30 7.11 10.83 0.79

5 1.23 2.11 1.80 9.37 35.63 2.21

80 0.91 2.58 0.65 7.53 58.46 6.92

60 0.59 2.76 0.74 6.21 97.77 6.86

120 0.84 2.34 0.70 4.08 62.10 7.18

4.42

3.34

4.95

6.43

8.38

In comparison with 201-TI chloride,administration of 201-TI-DADTP leads up to a many fold higher heart-to-organ ratios and with a gamma eamera,myocardium remains clearly visible several hours past the administration.

669

Wednesday, 4 September 1991

PO-4R1-45

PO-4R1-46

B. Cieynhens, C. Van Nerom, M, Hoogmartens, M. De Roo, A. Verbruggen. Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium.

P,H, Cox, M. de Sshrijver, ~, Pillay, H,N, Chia ~rom the Or,Oaniel den Hoed Cancer Center, Rotterdam, The Netherlands and Solon Nuclear, BirsFelden, Switzerland.

COMPLEXES OF 99roTeWITH ESTERS OF ALCOHOLISONITRILES: SYNTHESIS AND EVALUATION IN MICE.

THE MECHANISM OF LOCALIZATION OF To NANOCOLLOIOS AT SITES OF INFLAMMATORY OISEASE

Tc-99m MIBI(I) is a useful tracer agent for study of myocardial perfusion, ischemia and infarction. However, imaging can start only 60 rain p.i. due to pronounced hepatobiliary uptake. To promote clearance from the liver and excretion via the renal system, we have prepared 12 ester derivatives of alcoholisonitriles (CN-R-O-CO-R', R and R' being alkyl). The underlying idea was that such esters would rapidly cleave in vivo to more polar alcoholisonitriles with enhanced excretion rate. The ligands were synthesized via the following intermediates: NH2-R-OH-~. HCO-NH-R-OH-~ HCO-NH-R-O-CO-R'. Finally this N-formamide derivative was dehydrated by treatment with phosgene. Chemical idendity was confirmed by 2H and t3C NMR. Ligands were labelled with 99mWcby heating with pertechnetate in the presence of sodium dithionite. The complexes were analyzed for radiochemical purity on ITLC-SG. Electrophoresis was used to prove the cationic nature of the complex. The reaction mixtures were analyzed and purified by RP-HPLC on a Hypersil ODS column eluted with gradient mixtures of 0.05 M ammonium acetate pH 4 and acetone, After removal of acetone biodistribution of isolated HPLC-peaks was studied in mice (n =5) at 10 min and 30 min p.i. Compared to I, heart uptake of most compounds is lower, but it is dearly higher for the derivative with R=C(CH3)2-CH2 and R'=CH3 (II). Its activity in liver, blood, kidneys and lungs is nearly the same as for I, but its excretion to the intestines is faster. It is concluded that II and derivatives thereof merit further investigation as potential myocardial perfusion agents with improved biological characteristics.

The purpose of the study was to examine the meahsnism whsreby nanoaolloids accumulate in high concentrations compared with normal colloids in sites of inflammatory disease. The biodistribution of intravenously injscted To nanooolloid was investigated in normal sdult rats end in animals with terpentine induced intramuscular absees T sos, Following intravenous injection of To labeled nano~ co!laid seintigrams of the biedistributlon in normal and in abscess bearing animals were prepared at SO min,, i hr and 2 hrs post injection, Tissue localization in normal and treated animals was evaluated by aounting tissue samples and the biodistribution of Tc nanocolloid at the cellular level was confirmed by preparing electron photo mlorographs of both normal and abscess bearing tissue, The results showed that the small particle size Te nanoaolloid passes through the normal capillary membrane and accumulates in normal tissue to some extant contrary to the experience with the classical large particle size colloids. At the site of inflammation a higher accumulation of free To colloid particle in the interstitial spaae was observed together with a very clear accumulation in local phagocytes. It was concluded that the primary mechanism of localization of nanocolioids is due to the ready passage of this material through the normal as well as damaged capillary cellwalls. As with other colloids a degree of localization in phagocytes is also a contributory factor. The results suggest that naneaolloids can play e useful role in the early detection of focal inflammatory changes due to its capacity to pass wall compared to other radiopharmaceuticals,

PO-4R1-47

PO-4R1-48

K.Hamamot% T . F u j i i , Y.Kimura, K.Ochi, A.Akamune, N.Miyagawa, S.Tanada, and A . l i o Dept. Radiology,Ehime U n i v e r s i t y School o f Medicine, Ehime, Japan

Heal AV, Tyson IB, Courey M, Robb S, Docs J, Heal J. James A. Haley VA Hospital/University of So. Florida, College of Medicine, Tampa, Florida.

IN VIVO ADMINISTRATION OF DTPA CAN DECREASETHE ACCUMURATION OF INDIUM TO THE LIVER AND KIDNEY IN TUMORBEARING MICE The accumuratien o f i n d i u m - l l l (In) to normal tissues especially to the l i v e r is one of disadvantages of radioimmunoscintigraphy using In labeled antibody. One of the mechanisms is the r e l a t i v e i n s t a b i l i t y of the binding of the radionuclide and antibody. Free In may bind to carrying proteins such as t r a n s f e r r i n and hepatocytes may uptake these In. To decrease the accumulation of In to the normal tissues,we examined the e f f e c t of the chelate in tumor-bearing athymic mice. A monoclonal antibody to small c e l l cancer c e l l lines (Ka=2.28xlO moles/l) was labeled with In by DTPA. A f t e r intravenous administration of 37 kBq/lug of labeled antibody to tumor-bearing athymic mice,various doses of DTPA were injected i n t r a p e r i t o n e a l l y every day Although no s i g n i f i c a n t d i f f e r e n c e of b i o d i s t r i b u t i o n was detected between control and DTPA administered groups in the f i r s t day. Percent ID/g a f t e r 48 hours were as follows. DTPA blood 0 mg 6.7±0.8 0.5 mg 6.2±0.6 2.0 mg 5.8~0.5

liver 8.4±0.7 6.7m0.4 6.1~0.3

kidney 20.9±1.8 18.2±2.0 18,4±0.9

tumor 18.5±5.6 16.7±5.0 17.5±8.4

Administration of DTPA made i t possible to decrease the accumuration of In in the l i v e r a f t e r 2nd day. Scintigraphic studies also revealed apparent decrease of the hepatic uptake in DTPA administered mice.

670

EVALUATION OF BIODISTRIBUTION OF 131-I-~MFGI IN A NUDE MOUSE HUMAN COLORECTAL XENOGRAFT MODEL USING MULTIPLE IP ADMINISTRATION, UNLABELED Ab, IV OR PERITONEAL LAVAGE. At the present time, a Phase I/II clinical therap~ trial is in progress for colorectal and ovarian carcinOma requiring the IP ~nfusion of a low test dose followed by a high therapeutic dose with future repeat doses. However, three major probl6~ns exist: i) MoAb clearance in tumor is rapid (2-3 days Te i/2) allowing for irradiation of only superficial and small tumor masses; 2) repeat doses of more that two weeks are affected by HAMA; and 3) uptake on free cells in peritoneal cavity decreases available MoAb to the tumor. The purpose of this study was to evaluate multiple daily labeled MoAb infusion, use of cold MoAb, IV, prior to labeled Ab, IP, and pre and post-treatment lavage in order to enhance tumor uptake without increased normal t~ssue uptake. Results indicate: i) increased tumor uptake through four infusions with no significant increase in normal tissue; 2) no significant increase in tumor uptake with lavage but a significant decrease in normal tissue uptake; and 3) significant increase in tumor uptake with only a slight increase in uptake and rapid clearance in normal tissue with a pre-injection of cold antibody. These results possibly indicate that saturation of tumor or equilibrium may occur after 4 days of MoAb injection and that MoAb uptake in normal tissue is suppressed or cleared by cold Ab or lavage respectively. Thus increased tt~or uptake may be achieved for therapy withMoAb's.

Wednesday, 4 September 1991

PO-4R1-49

PO-4R1-50

E. Hcnze, M. Clausen, H. W. Gottfried, W. Brandes, T. Heuchemer, R. Welier, R. Ochsenkiihn, W.E. Adam, University of Ulm, Germany

tK. R. Ambrose, 2j. Kropp, tC. R. Lambert, 2H. J. Biersack, and ~F. F. Knapp, Jr., ~Oak Ridge National ,Laboratory, Oak Ridge, TN, and 2Univer. Bonn, Germany.

WHOLE BODY QUANTIFICATION OF Tc-99m ANTI-CEAMAK KINETICS IN PATIENTS WITH BLADDER CANCER

BACK DIFFUSION (BD) AND RELEASE OF METABOLITES ("X") CONTRIBUTE TO WASHOUT OF RADIOIODINATED BMIPP FROM ISOLATED RAT HEARTS (RH).

The in-vivo kinetics in man of a new anti-CEA monocIonal antibody (BW 431/26) was studied. This MAK was labeled directly with Tc-99m by a newly developed procedure without the need of additional eomplexing agents such as DTPA. 19 patients with proven urinary bladder carcinoma were studied so far 10 rain, 5 hrs and 24 hrs after i.v.-administration of approximately 20 mCi (740 MBq) of the Tc-99m MAK. Whole body scans were recorded simultaneously in anterior and posterior projection with a double head camera and a dedicated new interface that provides digital images in a 256 by 1024 matrix. Radioactivity concentrations of the whole body, the tumor and the various organs were quantified by computing the geometric mean of the activity measured within the according ROIs of the anterior and posterior scans, respectively. Whole body activity was decay corrected and normalized to the 10- min data = 100 %; ROI uptake is given in % of whole body activity. time 10 min 5 hrs 24 hrs whole body 100.0 _+0.0 97.6 _-+3.7 67.0 _+17.6 heart 11.4+2.6 11.0_+2.1 12.4-+ 3.0 liver 10.1-+3.3 10.4_+4.1 15,2-+ 7.7 spleen 1.9_+0.5 1.8-+0.6 2,2-+ 0.8 (left)kidney 1.3-+0.2 1.7-+0.2 3,3+ 0.7 bladder(tumor) 2.4-+5.0 2.7_+4.3 3.2_+ 4.4 Post-void bladder (tumor) uptake ranged from 17.4 % in one Iarge tumor to almost undetectable 0.5 % in smaller ones. Thus, despite the high in-vivo stability of Tc-99m anti-CEA-MAK for at least 5 hrs this tracer seems of limited value for detecting bladder cancer since at 5 hrs no significant bladder (tumor) accumulation has occurred and the increased post-void activity at 24 hrs might also reflect urinary contamination of excreted Tc-99m.

PO-4R1-51 P. Krumbiegel I, ri. Server 2, ~. Sprinz I I Zentralinstitut f~r Isotopen- und Stranlenforscn~u~g; 2 bniver sit~tskinderklinik Leipzig SODlbl~i[15t~]TAUROCHOLATE - A L~EW STASLL ISOTOPE PHAI~,~CEUTICAL TO I~WESTIGATE THE E~TERO~EPATIC BILE ACID CIRCULATIO~ NO~-IiWASIVELY Sodium [15~_Ttaurocholate (I) was synthesized by reacting L15t~_itaurine - which [~as obtained from sodim~ 2-bromoethanesulphonate and [JDi~]an~lonia -, eholio ~cid, and the coupling reagent ~EDQ. The identity and purlty were conflrtaeu oy d and ID~ I~5~ spectroscopy, n~%ss spectroscopy, and thin layer chrolrmtography using unlabeled tauroenolate and supposed impurities as reference substances. (I) was ad~ninistered orally (7 rr~/kg body mass) to a healthy proband first, in order to thoroughly study its reliability as a true marker of bile acid turnover. Urine and feces were collected over 7 days. Urinary 15t~ ~anounts (representative of deconjugated [ Pi~]tatu'ine) and ~ecal 15~i ~nounts (representative of el~;linated (I)) were estimated to find convenient sampling intervals for further studies. balance investigations have shown that (I) should be well suited for a non-invasive~ non-radioactive, simple urine test in pediatrics. ~ine Local Ethical Con~aittee has approved the study w~ieh is being continued including children with defects in enteronepatic bile acid circulation.

Iodine-123-1abeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is used for SPECT imaging of fatty acid uptake and clearance in patients. The relative levels of "X" and BD released arc relevant to the use of [I-123]BMIPP in humans. Radioactive "X" is the major component in the outflow of RH perfused with KrcbsHenseleirbuffer (KH) after administration of [I-125]BMIPP. To study effects of BSA on BD, RH (n=4 each) were perfused retrograde with KH or KIt with 0.4 mM BSA and/or 0.4 mM PAL. Lipids (Folch) from effluent (outflow) samples were analyzed by TLCSiO2 (benzene-dioxane-HOAc, 80:18:2; BMIPP, Rf=0.55; "X", Rr=0.35 ). In parallel studies, EL was extracted and analyzed from perfused RH (n=2 each) (PE-ether-HOAc, 70:30:1; BMIPP, R~=0.40; TG=triglycerides, Rr= 0.75). Major outflow lipids= BMIPP (FFA) and "X" and major EL= FFA and TG. Comparison was thus made between "X" and BMIPP release and EL profiles. Both BD (Table, % total by TLC) and EL profiles are affected by BSA and PAL, and BMIPP washout in vivo thus probably represents both BD and "X". Min. 3 5 7

KHOn~ FFA "X" 12 48 3 78 2 78

KH+ FFA 33 10 7

BSA "X" 44 70 77

KH+BSA+PAL FFA "X" 76 9 41 27 35 34

~Supported by OHER, U.S. DOE, under contract DE-AC0584OR21400 with Martin Marietta Energy Systems, Inc., and NIH Grant HL35500.

PO-4R1-52 R.M. Moresco, G. Lucignani, C. Rossetti, T. Best,

F.

Colombo, E. Deutsch and F. Fazio. ITBA-CNR, University of Milan, Institute H San Raffaele, Milan, Italy and BCRC, University of Cincinnati, Cincinnati, OH, USA. METABOLIC AND KINETIC EVALUATION POTENTIAL rCBF INDICATOR [Tc-99m]CB-PAO.

OF THE

[Tc-99m]cyclobutyl propylene amine oxime ([Tc-99m]CBPAO) is a new PAO derivate proposed for measuring rCBF. The tracer is easily prepared from an instant kit and stable in vitro for more than two hours. The kinetics of cerebral uptake and metabolism of [Tc-99m]CB-PAO were evaluated in male Sprague-Dawley rats. We measured: a) the blood timeactivity course of the parent compound and its metabolites after i.v. administration; b) the relationship between the regional distribution of the tracer in brain and the rate of rCBF; c) the regional cerebral rate of unidirectional influx (kl) and the unidirectional extraction fraction (E) of [Tc99m]CB-PAO. We found: 1) the absolute concentration of the tracer in blood immediately drops following an i.v. pulse injection; 2) the tracer undergoes 90% in vivo degradation in one minute; 3) the regional distribution of the tracer in brain correlates with the rate of rCBF only at low rates of flow and only for a limited period after i.v. injection. Autoradiography of brain sections revealed a pattern of distribution consistent with differences in local blood flow; 4) the unidirectional extraction fraction of the tracer is approximately 0.85. The tracer may be clinically useful for the semiquantitative assessment of cerebral perfusion with SPET.

671

Wednesday, 4 September 1991

PO-4R1-53

PO-4R1-54

~ih~k I. ,+Bl~ha V. ,+Ni~ek F. Faculty Hospital Vinohrady, Prague +3. Medical Faculty, Charles University, Czechoslovakia

M.S. Okarv.i, P. Adriaens, C. Van Nerom, G. Bormans, M. De Roo, A. Verbruggen. Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine U.Z. Gasthuisberg, K.U.Leuven, Belgium:

Prague

(99mTc) EHIDA, DTPA, bL~G-3 - CLEARANCE CURVE PROCESSING The study aims to get the quantitative clearanceparameterof the

routinely used radi0phar~ceuticals ~y kidney and hepat0hili~y scinti~aphy. This parameter is acquired by the analysis of the clearance curve from the R01 of the heart and its surroundings. The curve of this area is the su~ of 3 superimposed processes: a) Intravascular distribution b) Extravascular distribution c) Clearance In the let phase right after the administration of the radiopharmaceutical agent, all 3 processes take place; the intravascular distribution ceases first. The drop of the curve in the 2od phase is eausod by processes b) and c). After distrihutien in the extravascular spa~ is finished, the 3rd phase begins. In it, the s~ of the drop is determined by the clearance of the pha~centical from the entire distribution space. We analyse 0nly this part of the curve, on wich the drop is given only by processes b) and c). For the analysis the hiexpanential fitting F(x} = al*exp(-a2*x) + a3*exp(-a4*x) has been chosen, where the first exponential term dsscrihes the speed of the extravascular distribution and the second determines the clearance. The itarative ~ve~rg - ~rkvardt method has been used to fit the curve and the following parameters have been 0btaimed: a) T dst - the half-Ilia of the extravascular distribution in minutes b) E~D dst - the end of the extravascular distribution in minutes c) T clear - the half-life of the clearance in minutes

[mini dst dst clear

EHIDA (N = 218)

DTPA 102 (N = 99)

MAG-3 (N = 65)

2,95 -+ 0,50 17.68 + 3.10 32.17 -+ 18.01

2.68 +. 0.72 10.61_+ 2.53 49.75 +_ 25.66

2.22 ± 0.56 10.03 + 2.31 18.69 _+ 12.11

The relationshipand the muteal correlationsof all thee para~tars of the compounds used are statistically analyzed, the method and results discussed.

PO-4R1-55 J.-E. RYSER K. ROSE 1, R. JONES 1 A. PELEGRIN 2 M. PERIN, A.'DONATH, R. EGELI 3 arid R.E. OFFORIJ 1 Div. de M~decine Nuc14mire,d~pt de Biochime m~dicale1 et clin. de Chirurgiedigestive3, Centre M4~dicalet H0pital Cantonal Universitaires,Gen~ve; L.de Biochimie,Universit6,Lausanne2 A CHELATING AGENT CAN IMPROVE THE TUMOR-TONON-TUMOR ( T/NT ) RADIONUCLIDE RATIO OF IMMUNOSCINTIGRAPHY ( IS ) BY ACCELERATING THE EXCRETION OF FREE RADIONUCLIDE. As shown for biosynthetically-labeled 75Se-MABs free nuclide from the MABs catabolism can accumulate in NT (Ryser etal. 1990). Decreasing the free nuclide biological half-life will improve, in such a case, the T/NT ratios. We report here the effect of deferroxamine (Df) after the injection of SZGalabeled MABs. Anti-CEA MABs labeled by a site-specific method were injected into 6 pairs of mice bearing CEA + tumors. One mouse of each pair received daily Df subcutaneously and all mice were dissected 4-5 d after the MABs injection. The decrease of the dose recovery from 25.5 to 21.0 % ID/g in the tumors of the Df-treated mice was not significant (paired t test,p=0.34). In contrast Df induced a significant increase in the total T/NT ratio from 12.5 to 16.9 ( p < 0.05 ). We conclude that increasing the excretion of free nuclide co'uld be important in improving the results of IS. Reference: Ryser JE, Carrel S, Buchegger F, DonathA. Immunoscintigraphywith biosynthetically-labeled 75Se-antibodies.N.M.BioI.17:487-497(1990)

672

SYNTHESIS OF DERIVATIVES OF 99mTe-MAG3 WITH TWO AMIDE FUNCTIONS AND THEIR BIODISTRIBUTION IN MICE. 99mTc-MAG3 (___, CO at positions 1, 3, 5, CH2 at other positions) contains in its structure 3 am±de functions (-CO-NH-). To elucidate the importance of the number and position of these groups for the biological properties we have synthesized and evaluated six derivatives of A__ containing not more than two amides, respectively at positions l+3(_B), 1+5(C_C_¢3, 3+5(D__.1, 2+4(E.), l + 4 ( D and 2+5(G_). B, _C and D are direct derivatives of A, in which i am±de has been replaced by an amine. _E, _F and G_contain at least one inverted am±de. TcO [S-CH2- 1 -N- 2 - 3 -N- 4 - 5 -N-CH2-COOH] Exchange labelling of the S-benzyl protected precursors in the presence of Sn-tartrate pH 5 yielded each time a single radiochemical species with a retention time on HPLC slightly longer than that of A_. Biodistribution of HPLC-isolated peaks was studied in mice, using OIH as internal biological standard. B, C and D_D_,the direct derivatives, show a less efficient extraction from blood than A, which results in a lower urinary excretion : about 95, 45, 60 and 80% of OIH value at 10 rain p.i. for respectively A, B, C and D_. Also clearance through the hepatobiliary system is slightly increased. _, _ and _G mimic _A much better, as their urinary excretion at 10 rain p.i. is respectively 104, 94 and 90% of OIH value. Compared to A_ their renal retention is lower and blood clearance is nearly similar, except for G. The results show that derivative _E has the most ideal renal excretion characteristics and is superior to 99mTc-MAG3 in mice. Therefore it merits further evaluation in other animal species.

PO-4R1-56 i. Castanheira, C. Sawas-Dimopoulou, A. Paulo, N. Naves, L. Patricio, Dept. of Radioisotopes, LNETI, Sacavem, Portugal and NCSR "Demokritos" 153 10 Ag. Paraskevi Attiki, Greece BIODISTRIBUTION OF TC-99m-I,2,DIHYDROXYPROPYL-IPHOSPHONIC ACID AND M E C ~ I S M OF RENAL T ~ S P O R T

1,2-dihydro~propyl-l-phosphonic acid (DIOL), a derivative of the broad spectrum antibiotic phosphomycin, was obtained by acid hydrolysis of (-cis) 1,2-epoxypropylphosphonic acid, and characterized by IH-NblR spectroscopy. DIOL was labeled at pe 6.8 with Tc-99m. Biodistribution at various time intervals in mice showed a rapid bloo~ clearance (2.21±0.24% inj. Dose 1 hr p.i.) and urinary excretion (70.3±2.7% inj. Dose i hr p.i.). A 7.21±0.63% and 6.25±0.88% inj. Dose were respectively retained in the kidneys at i and 3 hr p.i. Whole body autoradiographies of mice showed that all the radioactivity is concentrated in kidney cortex, perhaps by binding on special sites of tubular cells. NO other organ in the body was visualized, In vitro protein-binding was 50%. In probenecid pretreated mice, t~e 1 hr-renal uptake decreased from 7.21±0.63% inj. Dose in controls to 3.36±0.30% and urinary excretion increased from 70.3±2.2~ in controls to 75.7±3.1% inj. Dose. Hyperurinaemia (by pretreatment of mice with uric acid and potassium oxonate) provoked retention in blood (7.93±0,65% inj. dose compared to 2.23±0.27% in controls). Biodistribution was not modified by acid-base imbalance. NO metabolism of the labeled product seemed to occur as the same results w e r e obtained by reinjection of the excreted radioactivity. The above results indicate that 99mTc-(Sn)-DIOL (pM 6.8) is selectively excreted by the kidneys and its tubular transport mechanism interfere with probenecid and uric acid.

Wednesday, 4 September 1991

PO-4R1-57

PO-4R1-58

OHW SCHONFELO, JC NOSSENT, A~ HOVESTADT Or,Oan~ol den Hood Cancer Center Rotterdam, The Netherlands

K.Schom~cker, W.G.Eranke, S.K.Shukla, G.S.Limouris, G.J.Beyer, K.Jantsch, R.M~nze, G.Kampf, R.Bergmann Clinic and Poliolinic of Nuclear Medicine of the University Clinics of ColegnW, Medical Academy Dresden

SP~CT IN NEUROPSYCHIATRIC LUPUS ERYTBEMATODUS USING 9BmTC HM PRO.

THE IMPROVEMENT OF TUMOUR LOCALIZATION OF F ~ I O A C T I V E METAL COMPOUNDS

Spect scanning o# the brain is a sensitive and noninvasive way to detect abnormalities of regional cerebral blood flow (rCBF) with the use of ggm-Tc Hm PAO. As neuropsyobiatrio [NP) lupus is often associated with vesuulopathy, we have used SPECT to study rCBF in twenty SLE patients with symptoms consistent with NP lupus. Results were expressed as uptake ratios with the corresponding area in the contralateral hemisfere serving as control. Uptake ratios < 0.95 were considered abnormal. Results: Fifteen patients (75%] had at least one area with low uptake ratios. Five patients also'had CT abnormalities, which were all detected by SPECT. When comparing uptake ratios with the objective NP findings of an independent consultant we found that seven of eight patients (8F.5%) with objective evidence of NP lupus had low uptake ratios, while eight out of twelve [75%] patients without objective abnormalities also had abnormal uptake ratios. Thus, SPECT scanning in NP lupus has a high sensitivity in detecting both clinical and CTscan abnormalities. Brain SPECT may have a potential role in NP lupus,

The most important problem in case of intravenous application of these metal ligand complexes is a strong radioactivity deposition not only in the tunlour but also in liver, bone, and blood. We tried to overcome this problems as follows: The preapplication of stable ions (Sr2+, A 3+, Ca 2+) resulted in a decrease of bone radioactivity by two orders of magnitude and only small radioactivity decrease in the tumour. Recently we proved that the compound ethylenediaminetetramethylenphoaphonate (EDTMP) is able to prevent the radioactivity deposition in liver by factor 20 after application of the above mentioned complexes. Furthermore we could show, that both the liver and the femur radioactivity background decreased if the tumouraffine radionuclides are applied as metal-DTPA-HSAcomplex. The tumour radioactivity is hardly changed in this case. The results are promising not only for tumour diagnosis but also for tumour therapy, as instead of garmna-emitting radionuclides in the applied complexes, therapeutic relevant nuclides may be used, under the main condition that their chemical properties resemble those of ytterbium. We obtained the first encouraging results after application of 90y-compounds in dogs and cats bearing melanoma or osteosarcoma.

PO-4R1-59

PO-4R1-60

Tyson ~, Heal A, Balducci L, Tenorio L, Zavosky L, McCarthy R, Silbiger M. USF/JAMES A. HALEY V A H O S P I T A L , TAMPA, FLORIDA

S. U n t e r s p a n n ; W. R u t z , U, F i n c k Radiological H o s o i t a l , O e p a r t m e n t of Nucl.Medicine, University Rostock, Gertrudenplatz, 0 - 2 5 0 n R o s t o c k , FRG

POLYPHARMACY WITH 131-I-RADIOLABELLED MONOCLONAL ANTIBODIES (131-I-MOAB) EFFICACY AND TOXICITY. Prior reports indicate optimal biological half times (t 1/2 biol), dose regimens, and side effects could be used with benefit. Occasional deviations frown expec~ ted findings raised the possibility that polypharmacy with 131-I-MoAbmay improve efficacy. Hypotheses, to test such speculations, a specific protocol using 131~MFGI, 131-AUAI, and HI7E2 with and without 131-Ilabel, was initiated. Review of prior data showed changes in MoAb excretion and HAMA titers suggesting the opportunity to manipulate the patient's response to an administrative regimen. Results show multiple 131-I-MoAb are readily tolerated by patients. All had recurrent apparently terminal tumor. No patient showed tumor mass reduction or tumor growth. Multiple sequential therapeutic doses of 131-I-}~MFGI as 30 mCi 131-I maintained a patient well, without tumor growth for 8 months. HAMA titer was initially low due to prior administration of up to 1 . 0 m g HMFGI unlabelled intravenously (I.V.) as a blocker. Satisfactory localization and absence of tumor growth were noted, with apparent normal 131-I-MoAb responses to administered doses intraperitoneally (IP) until the HAMA titers exceeded 15-20,000 ng/ml. These results suggest: successive therapeutic doses play a role in the management of patients with recurrent cancer; blockading doses of unlabelled MoAb by another route may enhance therapeutic efficacy of IP administered MoAb; and, since all patients on multiple 131-I-MoAb showed no toxic side effects and in two instances reported pain at the tumor sites 5-10 days past ad~ninistration, multiple MoAb doses are equal to or better than single doses with followup in i~4 months.

R E L A T I O N S B E T U E E N THE S T R U C T U R E OF M E T H A N E DIPHOSPHONATES ANO THE B[ODISTRTuqUTTO!I OF THEIR 9Om-Tc-COMPLEXES The aim of our i n v e s t i g a t i o n was to ~ind out bile r e ] a t i a n s s h i o b e t w e e n Lhe s t r u c t u r e of tile l i g e n d s and the b i o d i s t r i b b t i o n of t h e i r ggm-Tc-complexes. 18 9 g m - T c - l a b e l l e d m o n o - ( R 1 = H ) and 15 d i - s u b stituted methane diohosohon~tes w i t h the g e n e r a l f o r m u l a RI ( R ~ ) C ( P O Q H 2 ) 9 w a r e synt h e s i z e d end t h e i ~ i n - v i t r o an8 i n - v J v n behaviour were investigated in rats. The ~ o l l o w i n g r e s u l t s w e r e o b t a i n e d : I. 99m T o - c o m p l e x e s of m o n o s o b s t i t u t e d ligands showed a higher skeletal uotake than those oE d i s u b s t i t u t e d diphosphanates. 2. The £ S m - T c - c o m o l e x e s from l i g e n d s with a l o w e r m o ! e c u l a r w e i g h t r e s u l t ~n a h i g h e r s k e l e t a l u p t a k e in b o t h s u b s t a n c e c l a s s e s . In g e n e r a l v i e w the s k e l e t a l u p t a k e d e c r e a s e s w L t h i n c r e a s i n g m o l e c u l a r w e i g h t o# the l i g a n d s and the d e g r e e o[ s u b s t i t u t i o n , too.

673

Wednesday, 4 September 1991

PO-4R1-61

PO-4R1-62

C. Van Nerom, B. Cleynhens, M. Hoogmartens, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Radiopharmacy, U.Z. Gasthuisberg, K.U.Leuven, Belgium.

H. Vanbilloen, G. Bormans, C. Van Nerom, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

EVALUATION OF TWO NEW 99m-Te ISONITRILES IN MICE AND BABOON FOR MYOCARDIAL IMAGING.

COMPLEXES OF 99mTe WITH TETRAPEPTIDES CONTAINING 3 GLYCYL AND 1 ALANYL MOIETY

A practical shortcoming of 99mTc-MIBI (1) for myocardial perfusion studies is the pronounced liver uptake, which may compromise the detection of inferior wall defects and prohibits imaging early after injection. To promote excretion of 99mTc-isonitriles to intestines and/or urine and reduce the activity in the liver, we have developed derivatives of 99mTc-MIBIbearing an acetal or an alcoholester. It is supposed that in vivo hydrolysis of these apolar functions to respectively aldehyde or alcohol will yield more polar metabolites with enhanced excretion. Within the new compounds the complexes of 99mTc with ligands II and HI approach 99r"Tc-MIBIclosely in mice. Heart uptake of

99mTc-]] and 99mTc-III at 1 h p.i. is respectively 78% and 112% of that of I. Liver activity at the same moment is for both only 77% of that of I. Activity in other organs is similar. Therefore we have evaluated 99mTc-II and 99mTc-llI in a baboon and compared them with I and 2°lTl-thallous chloride (IV). Plasma disappearance is very fast and identical for I and m but somewhat slower for II and IV. Plasma protein binding, determined by ultrafiltration, is high (> 70%) for the 99mTc-isonitriles and negligible for IV. Heart uptake at 60 min p.i. is comparable for I and HI, slightly lower for II and clearly highest for IV. Urinary excretion at 60 min p.i. is high for I, II and Ill (25-50% of I.D.) which is in contrast with results reported for I in man. We conclude that further investigation of 99mTc-isonitriles looks promising and may result in an heart perfusion agent with more refined and more optimal biological behaviour.

In view of the interesting properties of some Cmethylderivatives of 99mTc-MAG3 ~ ) we now have studied all possible complexes of 99~Tc with tetrapeptides containing one Dor L- alanyl (A) and three glycyl moieties. The tetrapeptides were synthesized by conventional methods of peptide chemistry. They were labelled with 99mTc either by direct labelling at pH 12 (room temp) or exchange labelling (100°C) in the presence of Sn-tartrate pH 5. Labelling reaction products were analysed by RP-HPLC. Direct labelling of AGGG (!) yields two peaks, probably diastereomers, which after isolation convert rapidly to each other. Complexes of 99mTc with GAGG (-2), GGAG 0.) and GGGA (4_) are formed as one peak. HPLC-retention time of 4 is remarkably long, apparently due to increased lipophilicity resulting from substitution in the vicinity of the terminal COOH. Exchange labelling yields, for each !igand, the same main species as direct labelling, but also a peak eluting later on HPLC, which is assumed to be a cyclized 99mTc-tetrapeptide. In mice 2 and 3 show the best renal excretion characteristics, comparable with those of R. Only minor differences between D and L isomers are observed. Urinary excretion is somewhat slower for 1 (D and L) and clearly reduced for D-4 and L-4, possibly due to their higher lipophilicity. In baboon L-_2 shows the highest plasma clearance (66% of OIH value, versus 60% for 99~Tc-MAG3). Clearance is also high for L_1 and D-l, lower for L-3 and D-3 (about 35% of OIH value) and less than 20% of OIH value for L-4 and D-4. The results show that the position of the methyl substituent on the tetrapeptide chain affects to a high degree the biological behaviour. It also appears that some of these studied 99mTc-tetrapeptides show great poteiatial as a practical and suitable tracer agent for renal function studies.

PO-4R1-63

PO-4R1-64

H. Vanbilloen, G. Bormans, C. Van Heroin, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

T. Vandebrouck, B. Cleynhens, C. Van Nerom, G. Bormans, M. De Roo, A. Verbruggen. Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

DERIVATIVES OF 99~Tc-MAG3 AND 99mTc-TETRAGLYCINE WITH A TERMINAL ACETAL OR ETHER FUNCTION

COMPLEXES OF 99ZTe WITH MAGz, MAG3, MAG4, MAGs AND MAG6: COMPARISON OF LABELLING CHARACTERISTICS AND BIODISTRIBUTION IN MICE 99r~Tc-MAG3 (3_) is a 99mTc-mercaptoacetyl(MA)-tripeptide complex characterized by a high tubular extraction efficiency, a rapid excretion to the urine and a low uptake in the hepatobiliary system. To investigate the influence of the length of the peptide chain on the labelling characteristics and biological behaviour we have now compared the complexes of 99mTc with MAdiglycine (2), MAtriglycine (3), MAtetraglycine (4~, MApentaglycine (5) and MAbexaglycine (6). Exchange labelling with 99~,Tc was performed with the S-benzoyl protected ligands at 100°C in the presence of stannous tartrate pH 5. RP-HPLC on Hypersil ODS was used for analysis of reaction mixtures and isolation of the 99roTe-complexes. In competitive labelling experiments a mixture of I mg of each of two of the ligands ,,yas used and the relative amount of the two formed complexes was determined. MAG2 shows the highest ability to form a complex with 99mTc. From results of elecffophoresis experiments it is assumed that in 2 the CO0- is the fourth binding site for the TcO-core. For the other ligands complexation strength increases from 3 to 6. Competition between the terminal CO0- and the third amide for binding to TcO possibly diminishes with the distance between both groups. In mice 99mTc-MAG2 shows very poor extraction from the blood. This supports the hypothesis of a TcO-OOC bond. In the other compounds renal excretion diminishes and hepatobiliary handling increases from 3 to 6. Their retention time on HPLC indicates that also lipophilicity increases with the chain length. The results show that, within the studied series, 99mTc-MAG3 has the most ideal structural arrangement for efficient renal handling. It is also clear that contamination of ~ with 2, potentially provoked by decomposition during synthesis of the ligand or by prolonged heating during labelling, should be avoided strictly.

C =N-CHz-CH2-CH-(OCH~)z C =N-C(CH3)2-CH2-O-CO-CH3

II HI

Mercaptoacetyltripeptides and tetrapeptides are able to form stable complexes with 99~Tc, e.g. 99mTc-MAG3 (_1) and 99mTctetraglycine (2). To investigate the role of the terminal carboxylate in the complex formation and its contribution to the biological behaviour we have now studied derivatives of 1 in which Y= dimethylacetal [CH(OCH3)2,_la], diethylaeetal [CH(OC2Hs)2,1b] or ethoxymethyl [CH2OC2Hs,lc). Similar derivatives of 2, respectively _2a, 2b and 2c were added to establish the effect of an amino versus a thiol group. I

Tc0 [X-CH2-CO-N-CH2-CO-N-CH2-CO-N-CH2-Y] X=SH, Y=COOH :1 X=NH2, Y=COOH : _2

Direct labelling at pH 12 resulted in each case in one main radiochemical species whith a longer retention time on RP-HPLC than 1 and _2, which indicates a higher lipophilicity. In electrophoresis complexes la, lb and _lc move to the cathode over about the same distance at each pH. It is assumed that their charge is -1, which results from removal of 4 protons during binding of the TcO core. Complexes _2a, _2b and _2c are neutral in acidic medium but at higher pH they become negatively charged, apparently due to deprotonation of the amine which does not loose a proton upon binding to TcO. Results of the biodistribution study show the importance of the terminal COOH for renal handling. All tested new compounds are extensively cleared through the liver although some are only slightly more lipophilic than 1. Hepatobiliary clearance increases in proportion with the lipophilicity. Renal excretion is higher for corresponding derivatives of _2than of 1.

674

Wednesday, 4 September 1991

PO-4R1-66

PO-4R1-65 B. Cleynhens, P. Devos, G. Bormans, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

B. Woesle, F. Marschall, H. Wolf, E. Henze Department of Nuclear Medicine, University of Ulm, Germany

The results show that plasma clearance of 99mTc--PAHIDA and 99mTc-DTPA is identical in all studied species. It is concluded that 99mTc-PAHIDA behaves as an excellent agent for study of the GFR, but is not a suitable replacement for Hippuran for renal function studies.

P R E P A R A T I O N AND K I N E T I C I N V E S T I G A T I O N O F Tc-99m C O M P L E X E S W I T H C A R B O H Y D R A T E D E R I V A T I V E S AND AMINOALCOHOLS. Tc-99m labeled tracers for the investigation of the carbohydrate metabolism would be an enormous improvement of the diagnostic modalities in nuclear medicine. In this study we report our experiences in synthesis, quality control and application of Tc-99m-labeled carbohydrates and aminoalcohols. Technetium was complexed with the followingpolyfunctional ligands: 2-Amino-2-deoxy-D-glucosehydrochloride, L(+)-Arabinose, 2-Amino-2-deoxy-D-xylosehydrochloride, Aminoethanol, 1-Amino-2-propanol. The synthesis of the complexes was carried out by reduction of the Tc-99m-pertechnetate with stannous chloride in alkaline solution of pH 12. After neutralization the yield of complexed technetium compound was 85 - 95 % and thin layer chromatography gave a radiochemical purity of the complexes between 93 and 99 %. The in vitro stability of theprepared compounds was at least 4.5 hours.The specific distribution of the complexes m vivo was studied in rabbits and dogs. The liver uptake of all compounds testedin rabbits with additional administered insuline was always higher than ~ G l u c o s a m i n e in dog without medication The T c - ~ ~ ' 2 1 ~ "'~ [ 99m glucosamlne" complex, m i" ~ [ Kidney / ~ !I dogs showed also higher acu- I ~' 1,21 ~ .~. ~ /'~2,'7-~ I vlty after lnsuhne medication ~ A ~ ~"~" A partial involvement of this I 1 //'~.~ ] complex into carbohydrate/ L,/ ~ il metabolism has still to be ve- [ \ Kidney/Insuline [I rifled Another interesting fact is the kidney upt'ake of the ~ i J compounds: the kidneys of the rabbits show an activity maxi~ Livefflnsuline mum at 10- 20 min after injec- i ~ ~ 1 I tion with the sugars and meir •. derivatives as ligands. In con- I -~aver -~-,,-~,,_~ ] trast the kidneys of the dog I 0 20 40 60 80 100I show a steady rise of activity ~ __ Time [mini I with the Tc-99m-glucosamine complex until the end of acquisition.

PO-4R1-67

PO-4R1-68

H. Bayhan*, C. Aktolun*, K.M. Ktr**, E. Oztiirk*, B.Gfinalp* E. O~ur***, A. Aynm*, Y. Narin*, S. Dfindar* * Giilhane Military Medical Academy, Dept. of Nuct. Med., Ankara-Turkey ** Ankara University, Dept. of Nucl. Med., Ankara-Turkey *** G/ilhane Military Medical Academy, Dept. of Radiology, Ankara-Turkey

C.Aprile, U.Prati °, R.Saponaro, R.Campani*, D.Di Maio.

TC-99M-MIBI IMAGING IN THE PATIENS WITH INTRATHORACIC MALIGNANT TUMORS

SCINTIGRAPHIC AND INTRAOPERATIVE RADIOIMMUNOLOCALIZATION A F T E R A SINGLE NAB ADMINISTRATION. The aim of this work was to test the combined use of scinti~aphy(RIS) and intraoperative radioimmunolocalization(IORIL) after a single MAB administration.Sixteen pts,8 with primary colorectal cancer and 8 with suspected recurrence,were studied.After iv injection of i00130 MBq of lllIn aCEA,F(ab')2,RIS was performed on day 2 and 3;all pts but one,explored 22 days p.i,underwent surgery from day 2 to II.A 5xSmm NaI(TI) hand-held probe collimated in DENAL with a 3mm anterior window(MODELO 2,

E V A L U A T I O N O F 99~Tc-PAHIDA AS A R E N A L F U N C T I O N A G E N T IN D I F F E R E N T A N I M A L S P E C I E S 99mTc-PAHIDA(I) is a technetium-99m labelled derivative of hippuran(II) with rapid renal excretion in rats 0 N M 25, 1984, 1111). In dogs however, its plasma clearance is not significantly different from that of 99~Tc-DTPA(III) and therefore its further development has been abandoned. In view of possible interspecies differences and to not overlook a potentially valuable radiopharmaceutical for renal function studies we have compared the renal excretion characteristics of I, II and III in rabbits, a baboon and 5 human volunteers (approved by the local Ethical Committee). A small amount of t3tI-hippuran was coinjected as internal biological standard. In both the baboon and humans renograms of I were comparable to that of III but clearly different from that of II. Cumulative urinary excretion of I in humans (0-60') is significantly higher for I than for III, but only about 66% of the OIH value. Results of the 1-hour plasma clearance determination (as % of clearance of coinjected II) are summarized (table). 99r~Tc-PAHIDA Rat* Rabbit Dog* Baboon Human * literaturevalues

26.7 22.4 47.6 21.3 19.3

99mTc-DTPA 22.3 44.8 23.4 18.8

Tc99m-MIBI is a competing agent with TI-201 for myocardial perfusion imaging. Its uptake and kinetics in die patients with benign and malignant lesions of the lung have also been published. The aim of this study was to evaluate Tc99m-MIBI uptake in histopathologically proved intrathoracic malignancies. Twenty four patients were studied. Of the patients, 19 had primary lung cancer (11 had squamous cell carcinoma, 7 adenocarcinoma, 1 small cell carcinoma), t pulmonary metastasis of osteosarcoma, 1 pulmonary metastasis of renal cell carcinoma, 2 non-Hodgkin's lymphoma, 1 malignant thymoma. Chest radiogram and thorax CT scan were obtained before Tc99m-MIBI imaging. In all, but one, of the patients, the malignant lesion in the chest was solitary. The size of the smallest tumor was 40x35 mm, and that of the largest was 145x130 ram. None, but one, of the patients received radiotherapy and chemotherapy before imaging. Whole body and spot images were obtained 8-10 minutes after IV injection of commercial Tc99m-MIBI preparation. SPECT was performed in 8 patients. Results were classified as positive (focal abnormal uptake at the tumor site), and negative (no focus of activity in the involved region). Of the patients, 21 showed focal tumor uptake, whereas no increased uptake was detected at the tumor site in 3 patients (1 had adenocarcinoma, 1 squamous cell carcinoma, and 1 non-Hedgkin's lymphoma). Overall sensitivity of Tc99m-MIBI imaging for the detection of intrathoracic malignant tumors was found to be 87.5 perdent. Of the 3 patients who showed no tumor uptake, the first one who had adenocarcinoma received radiotherapy combined with chemotherapy before imaging, the second one who had squamous cell carcinoma had extensive tumor necrosis that was detected on CT scan, and the third one who had non-Hodgkin's lymphoma had received corticosteroid therapy for 3 months before imaging because of the misdiagnosis of pulmonary sarcoidosis. We concluded that Tc99m-MIBI imaging may be helpful for localizing inlrathoracic malignancies with the advantage of MIBI in kit form and optimum physical characteristics of Tc99m,and that further research is necessary to evaluate whether radiotherapy, chemotherapy, and corticosteroid therapy interfere with Tc99m-MIBI uptake.

,

L.Roveda °, M.Carena,

Fond. Clinica Lavoro, IRCCS, Nuel.Med.Serv; °Dept. of Surgery and *Radiology Inst., University-Pavia, Italy.

OHIS) was employed for IORIL;a T/NT ratio equal to or higher than 1.5 was considered positive.All 8 primary tumors were successfully imaged by HIS,while IORIL detected 7 of them(mean T/NT 1.81).Among the pts with suspected recurrence IORIL confirmed the true negative RIS results in one ease,the presence of recurrence in 3 cases with HIS positive(mean T/NT 2.24) while in 2 revealed a more diffuse involvement not surgically removable. In 2 pts with suboeelusion positive at HIS,IORIL ruled out the presence of tumoral involvement;similsr findings were observed in another case with equivocal HIS results in 2 different studies(mean T/NT I.IA).A pelvic recurrence positive at HIS was missed by IORIL probably because of the long time lapse allowed between administration and surgery(22 days).These preliminary data suggest that RIS and IORIL can be both performed after a single MAB administration with no additional dosimetry or time lapse,and that these techniques can increase the accuracy of radioimmunolocalization.

675

Wednesday, 4 September 1991

PO-4R1-69

PO-4R1-70

Ahtard AR, Fraser IA, Coventry. University.

Chappell MJ, Taylor DN, Baum RP, Godfrey K, Dykes PW, Bradwell AR. Walsgrave Hospital, IDRL, Medical Scheol, Birmingham. Warwick University Hospital, Frankfurt,FRG.

J.L.Baulieu, D.Guilloteau, C.Foulon, M.J. Ribeiro Barras, P.Bougnoux, L.Pourcelot, J . L a n s a e a n d J.C. Besnard. I N S E R M U316 Univ. Hosp. Tours France.

DFXKAMETHASONE IMPROVES ANTIBODY TARGETING OF COLORECTAL CANCER

E S T R O G E N R E C E P T O R S I M A G I N G IN B R E A S T C A N C E R W I T H IODINE-123 M E T H O X Y IODOVINYL E S T R A D I O L

Antibody targeting of tumours holds great potential for diagnosis and therapy but has been limited by low tumour uptake which is partly due to unsatisfactory tumour perfusion. I Blood flow in human colonic tumours transplanted into mice can be increased with dexamethasone. ~ We have therefore investigated the effect of this drug on antibody uptake in patients with colorectal cancer. 9 patients with 21 tumour sites were studied. Each patient was scanned 24 hours after 5-10mg (Group A) or 20mg (Group B) of high affinity anti-CEA monoclonal antibody BW431/26 labelled with technetium. A 24 hour course of dexamethasone (10mg I.V. , 16mg orally) was given and after 24 hours the scan was repeated using the same antibody dose. Uptake ratios for each tumour, before and after dexamethasone, were calculated from planar and tomographic images. The results are shown in the table: Group Antibody Uptake Ratio Uptake Ratio Dose Pre-Dex Post-Dex A (n=4) 5-10mg 2.48 + 0.62 2.17 +_ 0.61 ns* B (n=17) 20mg 1.50 +_ 0.89 2.16 +_ 1.10 p<0.0002 ~ * Paired t test (Uptake ratio: Mean + S.D.) 5 lesions in Group B, not seen on the first scan, were successfully imaged after dexamethasone. Our results indicate that, provided large doses of antibody are used, dexamethasone increases antibody uptake by colorectal rumours. Pre-treatment of patients with dexamethasone may therefore enable more effective targeting and therapy of tumours with antibody. i Jain RK, Baxter LT.(19HH) Cancer Res. 4B,7022-7032. = Braunschweiger PG, et a1(1983) Cancer Res.43,4757-61

The a i m of t h i s s t u d y was to a s s e s s t h e feasibility and interest of estrogen receptors (ER) s c i n t i g r a p h y u s i n g the r a d i o iodinated ligand 1-123 methoxy iodovinyl e s t r a d i o l (I-123-MIVE2). 1-123-MIVE2 was prepared according to a modified Hanson's method using a cold stannous t e r b u t y l d e r i v a t i v e as a p r e c u r s o r . After informed consent, 1-123-MIVE2 was i n j e c t e d into 12 w o m e n : g r o u p 1 : i n i t i a l e v a l u a t i o n of b r e a s t cancer (n = 7, m e a n age = 57 yrs, m e a n t u m o r size = 2.3 cm), g r o u p 2 : p o s t - o p e r a t i v e f o l l o w - u p (n = 5, m e a n age = 49 yrs). Imaging was p e r f o r m e d 2 hr a f t e r 1 - 1 2 3 - M I V E 2 (150 MBq) IV i n j e c t i o n by S P E C T of the chest (360 ° r o t a t i o n , 64 x 30 sec. steps), and p l a n a r views of the skull, spine and pelvis. P r i m a r y t u m o r was v i s u a l i z e d in 2/4 p a t i e n t s of g r o u p 1 w i t h ER+ tumor a n d in 0/3 p a t i e n t with ERtumor. Axillary lymph node metastases were detected in 1 p a t i e n t of group i a n d in 1 p a t i e n t of g r o u p 2. In 2 p a t i e n t s of g r o u p 2 w i t h ER+ p r i m a r y tumor, uptake in b o n e m e t a s t a s e s was evident. In terms of ER detection, sensitivity and s p e c i f i c i t y were r e s p e c t i v e l l y . 7 5 a n d 1.00.

PO-4R1-71

PO-4R1-72

~

R.Berberich~

,

E. BOCK, J. SCHEELE, Ch. WI'I-I'EKIND J. BAIR, epartment of Nuc ear Medicine, Surgery and Patholgy of the University of Erlangen-NiJrnberg, FRG

SENSITIVITY AND SPECIFICITY OF THE TC-99M-ANTI-CEA SCANS IN PATIENTS WITH LIVER METASTASES OF COLORECTAL CARCINOMAS

The use of Tc-99m anti-CEA-antibodies in follow-up of patients with celorectal carcinomas is widely accepted. The value in the detection of liver metastases is contoversa|discussed and is examined in this study. From anuary 1988 to february 1990 39 patients with colorectal carc nomas and suspected tumour recurrences or liver metastases were examined. 17 patients suffered from 43 solid liver metastases, which were removed by surgery and examined histopatho IogicaUy.565-740 MBq Tc-99m labelled murine menoclonal anti-CEA antibodies (2mg;l~G1 isotype, BW 4-31/26 kindly delivered from the BEHRING WERKE,FRG)were injected. Planar(5DO000cts) and SPECT images(64x64matrix)(SIEMENS ROTA,CDA) were collected 4h and 24h p.i. from the liver.Liver metastases were considered positive if they presented as totally hot areas or areas with initial cold but marginally hot rims. They were classified as negative if they presented as cold lesions. 4 lesions (9.3%) were found to be positive, 5 lesions with a rim sign(11.6%) and 25% of the metastases equivocal to normal liver tissue( 58,1%).9 lesions demonstrated to be cold spots(20.9%). Considering the number of metastases sensitivity was only 20%(9/43)and specificity of 100%. Considering the number of patients sensitivity was47% (8/17), specificity 100%. In patients with multiple metastases the uptake pattern was uniform in different lesions in 77.8%, mixed 22.2%. All metastases > 4cm diameter were negative. There was no correlation between antibody uptake , dedifferentiation, necrosis, CEA serum levels or immunohistochemistry and the results of the scans. The authors conclude, that the antibody uptake in CEA expressing metastases in the liver seems not to be dependant from necrosis, differentiation or CEA serum level. Because of slight correlations to the size of metastases the perfusion has to be discussed as an important parameter of antibody uptake. Presumably radionuclides with longer physical halflifes render better results.

676

C.Keweloh,

Abt. for N u k l e a r m e d i z i n versih&tsklinik, D 6650 PITFALLS LABELLED

E. O b e r h a u s e n der R a d i o l o g i s c h e n Homburg/Saar

IN I M M U N O S C I N T I G R A P H Y MONOCLONAL ANTIBODIES

WITH

Uni-

TC-99M-

In the l a s t four years we investigated more t h a n 250 patients suffering from a colorectal tumor w i t h the Mab BW 431/26. W e s t u d i e d too a b o u t 40 p a t i e n t s w i t h m a l i g n a n t m e l a n o m a s w i t h the M a b 575/931. The r e s u l t s of t h e s e i m m u n o s cintigraphies with both Mab's were convincing and gave proof of the g r e a t c l i n i c a l v a l u e of this method. In some c a s e s we saw a slightly i n c r e a s e d u n s p e c i f i c a c c u m u l a t i o n in the bowel. This fact is also known from literature. In this paper we like to p r e s e n t some c a s e s of false p o s i t i v e a c c u m u l a t i o n s due to o t h e r r e a sons. M o s t of the false p o s i t i v e c a s e s w e r e due to i n f e c t i o u s l e s i o n s as w e l l in the b o w e l as in the e x t r e m i t i e s (osteomyelitis and abscesses). In o t h e r c a s e s this w a s c a u s e d b y a f r e s h wound or b y p r o c e s s e s of r e p a r a t i o n in scars. TO e x c l u d e a b i n d i n g of the M a b B W 4 3 1 / 2 6 to h u m a n g r a n u l o c y t e s w e d i d in v i v o l a b e l l i n g s of a l e u c o c y t e m i x t u r e in 5 n o r m a l subjects. C o m paring these l a b e l i n g efficiencies with those done w i t h the M a b 2 5 0 / 1 8 3 w e f o u n d v a l u e s b e t w e e n 1 a n d 2,5% a f t e r 1 a n d 2 h o u r s of i n c u b a tion, a n d w i t h the a n t i g r a n u l o c y t e M a b b e t w e e n 38 a n d 45 % w e r e m e a s u r e d . So w e b e l i e v e t h a t false p o s i t i v e r e s u l t s c a u s e d b y i n f e c t i o u s are due to an a c c u m u l a t i o n of m a c r o m o l e c u l e s . The p r e s e n t e d cases proof that accumulations of tumor a s s o c i a t e d Mab's can also occur by other reasons. T h e r e f o r e o t h e r diseases, which may i n d u c e an a c c u m u l a t i o n of the M a b ' s by other reasons, m u s t be e x c l u d e d .

Wednesday,

4 September

PO-4R1-73 Ll.Bern~, C,Duncker, I.Carri6, M.Estorch, G.Torres, J.R.Germ~, D.Duncker. H o s p i t a l de Sant Pau, Barcelona. Spain.

PO-4R1-74

BONE MARROW REGENERATION AFTER HORMONE THERAPY DETECTED BY ANTIGRANULOCYTE ANTIBODY SCANS IN PATIENTS WITH BONE METASTASES FROM PROSTATIC CARCINOMA.

NATURAL HISTORY OF THE NEUROBLASTOMA AFTER MIBG.

1991

O. Caballero and J, Ferris. Hospital La Fe. Valencia. Spain.

response in all 4 patients. Bone m a r r o w r e g e n e r a t i o n , as p a r t of the response to therapy in these patients, can be demonstrated by means o f AGAb bone m a r r o w s c a n s when bone s c a n s do n o t show c h a n g e s .

MIBG-scan is a exploration with high sensitivity and specificity in diagnosis of neureblastomas. The dai~ ly use in children have changed the protocol of study to these group of patients, actually related to the stage of the disease when the MIBG-scan is carriet out. The positivity or normality result suggest a different way in order to indicate other explorations and the diagnosis and treatment orientation. The aim of this paper, has been analized in a large serie, the influence of the results of the MIBG in the study, diagnosis and treatment of these patients. We have studied 64 patients with clinical, ultrasound or x-chest suspicium of neuroblastoma. The radiopharmaceutical: 123I-MIBG (i00 uCi/Kg) was i.v. administrated and gammacamara images were obtained as fellowi: head, thorax, abdomen and pelvis at 3 hours, 24 hours, and eventually 48 h. Histopathology: 46 Neuroblastoma and 18 other diagnosis. MIBG-scan: MIBG positive 45/46 of neuroblastomas. MIBG normal: 18/18 of other diagnosis. Urine catecholamines: positive: 40/46 of neuroblastoma. TAC. Scan: 62 inexpecifique mass. Conclusions: 1. Indication of MIBG-scan has been: clinical, ultrasonic, or radiologic. 2. The positive index of MIBG in our serie has been 98Z. 3. MIBG (+) has oriented the diagnosis towards neuroblas~ toma, so that in this subgroup the number of cases which catecholamines and TAC studies was ordered was greater. 4. MIBG (-) has oriented the diagnosis of other pathological process.

PO-4R1-75

PO-4R1-76

CASARA D, RUBELLO D, SALADINI G, CALZAVARA F.

Catozzi L . * , Scambia G.§, Giovannini G.*, Pelizzola D.*, Uccelli L.% Barozzi R.*, and P i f f a n e l l i A.* * Chair of Nuclear Medicine, Univ. of Ferrara (ITALY) § Inst. of Obst. and Gynec., Catholoc Univ., Rome(ITALY) PROTO-ONCOGENE p21ra.__.ss AUTORADIOGRAPHIC DETERMINATION: EXPRESSION AND CORRELATION WITH CLINICAL PROGNOSTIC PARAMETERS IN BREASTAND OVARIAN CANCER. The ras proto-oncogene family (Ha-, Ki- and N-ras) encode for a 21,000 d protein (p21) and results amplified and overexpressed in some human breast and ovarian carcinomas. In previous studies i t was demonstrated that ras activation was not due to point mutations or structural a l t e r a t i o n s in both types of tumor. So, in the present study, we measured the expression of p21ra___ss in two groups of tumors from breast and ovarian cancer patients and we c o r r e l a t ed p21 levels with some clinical prognostic factors. We employed SDS-page immunoblotting followed by computer-assisted image analysis of autoradiographs. In breast cancer we observed that in 41.5% of primary and in 78% of metastases p21ra~s was highly overexpressed as compared to normal tissues whereas in benign lesions only in 18% of cases was the protein present and at low levels. In the ovary no case of cysts or benign tumors expressed high levels; in 36.8% (p
We h a v e shown t h a t bone m a r r o w i n v o l v e m e n t can be assessed by 99mTc-antigranulocyte monoclonal antibody (AGAb) BW 2 5 0 / 1 8 3 s c a n s (JNM 1 9 9 0 ; 3 1 : 1 4 5 0 - 5 5 ) . To a s s e s s r e s p o n s e t o treatment, we s t u d i e d five patients with p r o s t a t i c carcinoma and bone m e t a s t a s e s who underwent hormone therapy with antiandrogens. Conventional bone scans with 99mTc-MDP and A G A b b o n e m a r r o w s c a n s w e r e p e r f o r m e d in all patients before treatment a n d at 6 m o n t h s of treatment. B o n e m e t a s t a s e s w e r e s e e n in t h e b o n e s c a n s in all patients before treatment: diffuse involve-ment in 3 p a t i e n t s a n d m u l t i p l e foci in 2 patients. Correspondent bone marrow i n v a s i o n was o b s e r v e d i n t h e m a r r o w s c a n s i n

all

p a t i e n t s . At 6 months o f treatment, bone

scans showed (reduction in patient. Bone

only slight improvement the number of sites) in 1 marrow scans showed marked

improvement (reappearance o f bone marrow in extensive regions without bone marrow in the baseline study) in 3 p a t i e n t s and s l i g h t improvement in I p a t i e n t , r e l a t i n g t o c l i n i c a l

Radiotherapy and Nuclear Medicine Department, Genera] Hospital of Padua, Italy. MAY A N E W T N M C L A S S I F I C A T I O N BE P R O P O S E D IN S T A G I N G OF B R E A S T C A N C E R ? THE R O L E O F I N T E R N A L M A M M A R Y L H Y I ~ H O -

SCINTIGRAPHY (IML). To current time, TNM evaluation of lymphatic invasion in breast cancer (HC) is based on axillary node involvement (NI). The present study wa~ undertaken to demonstrate the importance of internal mammary NI in TNM of BC. During a 7 year period, 526 female patients (pts) with BC were studied. All pts were treated by surgery and radiotherapy, 174 also by hormone/chemotherapy. On the basis of classical TNM, 105 pts were classified as stage I °, 247 stage II ° , 147 stage III° and 27 stage IV ° . IML resulted pathologic in 24% of all Eases and in 12% of pts with histological negative axi]]ary nodes. Moreover, in 258 pts the IML-results were correlated to the appearance of bone metastases "(M), showed by hone scans yearly performed during'a 5 year. follow-up. In IML-positive pts, bone M resulted more frequent than in IML-negative pts (58% vs 42~, p < .01). Regarding to the 5 year survi val, a significative difference between IML-positive and IML-negative pts was observed (60% vs 85%, p ~ .01). In conclusion, our data strictly suggest that IML represents a sensitive indicator of internal mammary lymph no de status in pts wirh BC. Long-term results in our series indicate the important prognostic value of IML for these pts. IML is recommended to be performed in all pts with BC, to better define the lymphatic involvement for TNM staging and thus the therapeutic approach in BC.

677

Wednesday, 4 September 1991

PO-4R1-77

PO-4R1-78

CORBETT, RP. PEACOCK J. MELLER ST. Department of Paediatries, Royal Marsden Hospital and Institute of Cancer Research, Sutton, Surrey, U.K.

l£Cdp~a*, M.fiasparini*, E.Seregni*, N.fiavoni**, A.Marini*~ , LMaffio]i* and G.L.Buraggi* * National Cancer Institute - Milan, Italy ** I10bshGyn.Clinie University of Milan, Italy

INHIBITION OF 1251METAIODOBENZYLGUANIDINE (mIBG) UPTAKE INTO NEURBBLASTOMAMONOLAYERSBY ANTIEHETIC

RADO IM I MUNOTHGRAPY (RI?) OF OVARIANCANCGRWITH 1-131 M0vI8: PRPL ,IMINARY RESULTS MOvl8 is a monoclonal antibody against ovarian cancer selected and characterizated at the National Cancer Institute of Milan, Italy (1). The "in vivo" biodistribuUon of MOvl8, radiolabelled with 1-131, has been investigated using the i.v. and the i.p. route of administration (2). The obtained promising results led us to carry out a clinical trial of SIT in ovarian cancer.Patients with minimal residual disease ,showed by 2nd look procedures after debulking surgery and first-line ehemntherapy, have been engaged in this study. The outline of the trial was: 1) checking of abdominal perfusion with Tc-99io maeroaggregates before RIT; 2) during thyroid-blocked conditions, i.p. administraUon of 1-131 MOvl8 with about 2000 ml of saline solution; 3) checking of MOvl8 biodistributinn with whole-body scan 4-5 days after RIT;4) evaluation of toxicity of RIT and }lAMAprodueUnn with blood samples ; 5) 3rd look procedures 30 60 days after the treatment to evaluate the results of RIT. At present, 8 patients entered the study. They were affected by serous (6), papillar (1) and endometrioid (1) carcinomas. Mean adminiskerd activity of I 131 was 3700 MBq corresponding to about 15 mg of MOvl8 No clinical or haematological toxicity has been noted. At present 5/8 patients have been already submitted to 3rdlook. 4 patients showed tumor progression and died about 3-9 monLhs from the RI'I" One patient showed complete remission (follow-up= 4 months). 3rd-look evaluation of the remaining 3 patients wilt be performed in the next future.

AGENTS In treating neuroblastoma, the rapid administration of 1311mIBG ~200mCi) frequently causes vomiting. It is known that mIBG is concentrated in neuroblastoma by a mechanism (uptake I), which is blacked by tricyclic antidepressants, monoamines and serotonin. Most oral antiemetics possess a tricyclic backbone, or inhibit receptor-ligand interaction of dopamine or serotonin. This study was undertaken to determine whether antiemetics inhibit mIBG uptake. 5K-N-BE(2C) monolsyers were preincubated for ½-hour with antiemetic aqents (see table), followed by incubation with 1251mIBG (I0-7M) for 2-hours; the cells were then washed, trypsinized and counted on a gamma counter. Results are shown in the table:

Drugs tested Chlarpromazine (Sigma) Prochlorperazine (Sigma) Haloperidol (Sigma) Metoclopramide (Sigma) GR.38032F (Glaxo) BRL.Q3694A (5mith-Kline Beecham)

Molar concentration of drug to inhibit mIBG uptake by.50% (IDSO) 7.0 x lO-~M 5.3 x 10-7M

I .7 x I0-7M no i n h i b i t i o n < I0-5M no i n h i b i t i o n ~ 1 0 - 5 H no i n h i b i t i o n ~ I O - 5 M

This study i n d i c a t e s t h a t phenothiazine and butyrophenone drugs should be avoided in p a t i e n t s receiving mIBG. However, the dopamine/serotonin (SHT 5) receptor antagonists do not i n t e r f e r e with mIBG uptake at c l i n i c a l l y relevant concentrations.

1) MiotU S, Canevari S, Menard S el all.lnt J Cancer 39:297-303, 1987 2) Crippa F, Buraggi (iL,Di Re E et all. Cur J Cancer. Accepted.

PO-4R1-79

PO-4R1-80

R Dierckx, A Dobbeleir, Ph Franken, PP De Deyn, J Vandevivere Middelheim General Hospital, Born Bunge Foundation U.I.A., Antwerp, Belgium.

H.Estorch, I.Carri6, L.Bern~, C.Duncker, G.Torres, D.Duncker, C.Alonso, B.Ojeda. Hospital de S a n t Pau, B a r c e l o n a . S p a i n .

THALLIUM-201 AND Tc-99m pRELIMINARY FINDINGS

COMPARISON OF CARDIOTOXICITY OF DOXORUBICIN AND MITOXANTRONE BY MEANS OF ANTIMYOSIN ANTIBODY STUDIES.

MIBI

BRAIN

SPECT

:

Recently, O'Tuama et al reported on Tc-99m MIBI (Methoxyisobutylisonitrile) SPECT imaging of a pediatric brain tumor, We examined 4 patients with Tc-99m MIBI using a three-head rotating gamma camera system (Triad 88, Trionix) equipped with a high-resolution fan-beam collimator. Image acquisition was started immediately after intravenous injection of 25 mCi Tc-99m MIBI, with 3° a n g u l a r steps, 120 ° rotation for each detector, 60 seconds per image. Data were compared with the images acquired immediately after intravenous injection of 4 mCi Thallium-201, using the three-head SPECT system equipped with a low-energy ultrahigh-resolution parallel collimator. Tc-99m MIBI SPECT in a patient presenting with pituitary adenoma showed higher tumor to non-tumor uptake of 10/1 when compared with 4/1 for the Thalliura-201 brain SPECT. However, in another patient both examinations failed to show accumulation in a large glioma. In one patient clinically suspected of tumoral invasion, finally diagnosed as an infarction, both examinations were normal. Finally, in a patient presenting with glioma, differentiation between tumor and edema was similar in both studies. The 4 studies with Tc-99m MIBI showed better spatial resolution when compared with Thallium-201 images, but interference due to free pertechnetate activity in the choroid plexus was present. These parallel findings with both techniques further support a possible role for Tc-99m MIBI in the investigation of brain tumors.

678

To assess chemotherapeutically induced myocardial damage, we performed In-111 antimyosin antibody scans and ejection fraction (EF) m e a s u r e m e n t s i n 32 women w i t h b r e a s t c a n c e r who had r e c e i v e d chemotherapy including anthracyclines (doxorubicin or mitoxantrone). Antimyosin uptake was quantified by means o f a h e a r t t o l u n g r a t i o (HLR). I n 17 p a t i e n t s treated with doxorubicin (500 mg/m2), EF b e f o r e c h e m o t h e r a p y was 60.6±7%, and after chemotherapy was 50.5±9% (p=O.O01). Seven o f 17 p a t i e n t s p r e s e n t e d d e c r e a s e i n EF ~IO%. Three o f these p a t i e n t s presented w i t h symptoms of congestive heart failure. Antimyosin uptake in the myocardium was observed in all patients after chemotherapy. Mean HLR was 2 . 0 3 ± 0 . 2 6 . I n 15 p ~ t i e n t s treated with mitoxantrone (120 mg/m~), EF b e f o r e chemotherapy was 58.4±7%, and after c h e m o t h e r a p y was 56.5±6% ( p = N S ) . One o f 15 patients p r e s e n t e d w i t h d e c r e a s e i n EF Z10%. Antimyosin uptake in the myocardium was observed in twelve of 15 p a t i e n t s after chemotherapy. HLR i n a n t i m y o s i n studies was 1.77±0.19 (p
Wednesday, 4 September 1991

PO-4R1-81

PO-4R1-82

G.S.Limouris a, 3.C.Fetsi b, H.H.Constantoulakis% 5.K.Shuklad, K . ~ a.Nuc Med Sec,Areteion Univ Bosp,Athens b.Haemat.Lab "Agia Sophia",Athens Childr Hosp e.Athens Ned Seh d.Nat Res £ounc(CNR),Rome e. Nuel Ned Dept,univ olin Cologne.

M Gas~arjnjt M.R. Caste]lani*, P Crippa*, L. Maffioli*, ~]. Seregni*, L [~aharinL J.Rayner and GL, I3araggi*, *Nuclear Medicine Division 'Radiologicat Department "E" National Cancer' Institute Milan Italy.

ON THE EVALUAIION OF INTERLEUCIN-2 BREAST AND PROSTATE CANCER.

SERUM LEVELS

IN

The importance of interleucin-2 (IL-2) steams from the fact that it can regulate the immune Function. Therefore its serum levels could inform on the general immune staLus of the malignancy. The aim of this sLudy is to evaluate the biological significance of IL-2 serum levels in metastatic or not malignancies. 47 breast cancer patients aged 41 to 63 years (23 among them w i t h bone metastases), 29 prosLata cancer patienLs aged 54 to 71 year (10 among them w i t h bome meLasLases) and 13 normal conLrols were examined. In each blood sample the absoluLe number o f leucocytes were measured. No paLienL had been p r e v i o u s l y t r e a t e d w i t h ehemo- or r a t i o - therapy. P e r i p h e r a l blood mononuc l e a r c e l l s were separated from whole blood by c e n t r i fugaLion on Leuco PREP (Beeton Dickinson, USA) and p r o p e r l y c u l t u r e d . IL-2 was measured by radioimmunosssay (MEDGENIX-BELGIUN), a l l samples were assessed in d u b l i care at Lhe same time and Lhe values were expressed as U per ml aL each Lime p o i n t . Data were s t a t i s t i c a l l y analyzed by S t u d e n t ' s Lest and c o e f f i c i e n t o f c o r r e l a Lion. Blood c o l l e c t i o n in Lhe m e t a s t a t i c cases was p e r formed j u s t b e f o r e the b e g i n n i n g o f the f i r s t c y c l e o f

radiotherapy. Our r e s u l t s i n d i c a t e t h a t IL-2 l e v e l s are s t a t i s t i c a l l y s i g n i f i c a n t (p< 0.01) lower to those o f Lhe conL r o l group. On Lhe c o n t r a r y , no important changes in IL-2 blood c o n c e n t r a t i o n s have been observed between Lhe b r e a s t and peostata cancer groups. Lower c o n c e n t r a t i o n s o f IL-2 were shown in a l l (100%) metastatic patienLs. We conclude thaL Lhe lower IL-2 c o n c e n t r a t i o n s tn meLastatic cancers could be r e l a t e d Lo an immune d i s f u n c t i o n beeing more poLent in metasLatie processes.

CALIJUM 67 SCINTIGRAPHY(Ca) OF TIlE MEDIASTINUMIN PATIENTSWITH HODGKIN I,YMPHOMA:CORRELATIONWITHMAGNI
PO-4R1-83 U Haberkorn, LG Strauss, A Dimitrakopoulou, R Engenhart, J Romahn, F Oberdorfer, S Ziegler, G Wolber, WJ Lorenz Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg

OS H o e k s t r a , PC H u l 3 g e n s , GJ O s s e ~ k o p p e l e , R G o l @ i n g I, H J M M a r t e ~ s ~ J D M H e r s c h e i d ~ A v a n L i ~ g e n b a n d G J J Teule.2 Free U n i v e r s i t y Hospital*, R a d i o N u c l i d e C e n t e r , De B o e l e l a a n 1117, 1 0 8 1 H V Amsterdam, the Netherlands.

F-18-DEOXYGLUCOSE (FDG) UPTAKE IN IRRADIATED PATIENTS WITH RECURRENT COLORECTAL CANCER. Twenty patients with recurrent colorectal carcinoma were studied prior to a combined photon-neutron therapy (40 Gy photons, 10 Gy neutrons). The acquisition was performed 1 hour after i.v. administration of 3 0 0 - 4 4 0 MBq FDG In all patients a~ follow up study was done after photon therapy and 1Z~patients were examined 6 weeks after the end of the combined therapy. The tumor volume was calculated from CT cross sections in 10 patients and the tumor growth rate was determined assuming an exponential function. Furthermore, blood samples were taken immediately before the PET examination to measure blood glucose and CEA levels. We found only a low correlation between plasma glucose level and FDG uptake. Although a good palliative effect was seen in all patients, a significant decrease in FDG uptake occured in only 50%. This can be explained by radiation induced inflammation. Inflammatory reactions and resting tumor tissue cannot be differentiated. We suggest that an examination interval of 6 to 9 month i8 required for a cut off in this differential diagnosis. An increase in FDG uptake was associated with a positive growth rate, whereas a decrease was not necessarily correlated with a negative growth rate. This fact may be due to radiation necrosis not visible in the CT scan. An elevated FDG accumulation together with normal plasma CEA was found in 14 of 41 examinations, whereas normal FDG accumulation was associated with an increased plasma CEA only in two cases. This indicates that PET with FDG is more sensitive than the plasma CEA level for the follow up of recurrent colorectal cancer.

C O M P A R A T I V E I M A G I N G W I T H 18-FDG A N D 6 7 - G A C I T R A T E (67Ga) IN M A L I G N A N T L Y M P H O M A M u l t i d r u g c h e m o t h e r a p y is u s u a l l y m o n i t o r e d by radiological methods w h i c h cannot d i s t i n g u i s h b e t w e e n v i a b l e tumour, necrosis, and fibrosis. Since m e t a b o l i c changes p r e c e d e the a n a t o m i c a l response to treatment, prognostic criteria provided by f u n c t i o n a l s t a g i n g m i g h t be m o r e reliable. We compared 67-Ga and 18-FDG a c i n t i g r a p h y in p a t i e n t s w i t h H o d g k i n ' s d i s e a s e or non-Hodgkin lymphoma. Planar images of d o c u m e n t e d r a d i o - l o g i c a l masses w e r e m a d e 45 m i n a f t e r 185 M B q 18-FDG (using a 511 k e V collimator), and I w k a f t e r 185 M B q 67-Ga. I m a g i n g was performed in p a t i e n t s with a residual mass (n=12); b e f o r e t r e a t m e n t and a f t e r 2 courses of chemotherapy (n=16), while 6 w e r e a l s o s t u d i e d a f t e r the first course (18-FDG only). The s c i n t i g r a p h i c a p p e a r a n c e of p a t h o l o g i c a l m a s s e s W e r e b a s i c a l l y the same w i t h b o t h tracers. In some p a t i e n t s w i t h cervical p a t h o l o g y or a r e s i d u a l mass, 57-Ga u p t a k e in c e r v i c a l or h i l a r nodes was more pronounced. C o m p l e t e remissions, as d e t e r m i n e d by r a d i o l o g i c a l methods, c o u l d be p r e d i c t e d from the change in 67-Ga and 18-FDG t u m o u r u p t a k e after 2 chemotherapeutic courses. Even after i course a sharp decrease of m e t a b o l i c tumour a c t i v i t y could be documented. We c o n c l u d e t h a t in m a l i g n a n t lymphoma, 67-Ga and 18-FDG g e n e r a l l y p r o v i d e the same information. Both tracers can be u s e d for t r e a t m e n t m o n i t o ring, w h i l e the short TI/2 of 18-FDG allows its repeated use in v e r y e a r l y stages of c a n c e r treatment.

PO-4R1-84 I

''

]

I

679

Wednesday, 4 September 1991

PO-4R1-85

PO-4R1-86

H.O.Keweloh, U.Hildebrandt Abt. f . Nuklearmedizin der Radlologischen Universit~tsk l i n i k und Chirurgische U n i v e r s i t ~ t s k l i n i k D-6650 Homburg / Saar

M.V. Knopp,L.G. Strauss,H. Sischoff', U. Haberkorn,D. Branscheid*, J. Doll, G. Wolber, H. Hoverath,W. Maier-Borst,G. van Kaick DeutschesKrebsforschungszentrum,instituteof RadioMgyand Pathophysiology,*ThoraxklinikRohrbach;Heidelberg,Germany

EARLY DETECTION OF LOCAL RECURRENCESAFTER RESECTION OF REC$O-SIGMOID CANCER Immunoscintigraphy (IS) has been proven as a valuable method for the detection of tumor metastasis with good results and minimal risk f o r the patients. However, mainly due to the advanced state of the disease of most patients, therapeutic relevance has been quite small so f a r . Here, we like to present preliminary results of an ongoing study f o r the early detection of local relapses a f t e r preceding surgery of recto-sigmoid cancer. This subgroup of cancer patients was chosen because of the high rate of expressing CEA and t h e i r high prevalence of developing a local recurrence of t h e i r disease. Routinely those patients are being examined every three months by means of endosonography.Due to the risk of inducing HAMAs (human antimurtne antibodies) as well as i t s great displa~ IS is only done Tn patients with a suspicious weak-echo-area in endosonography. So f a r , six patients have been enrolled in this study. Each one received I GBq 99m-Tc-labelled Mab BW 431/26. Planar and SPECT-imaging was done 5 and 24 h p . / . In a l l patients Mab-accumulation was found corresponding anatomically to the endosonographically suspicious area. Surgery and histopathoiogy proved l a t e r on the accuracy of the tmmunosctntigraphlc r e s u l t . Here, the importance of SPECT must be stressed. Due to the proximity of the bladder and the small diameter of the local recurrences observed, in 3/6 patients relapse could not be detected by planar imaging alone. Conclusion: IS in combination with endosonography f o r the early~ction of local recurrences of recto-sigmoid tumors seems to be a promising diagnostic method leading to therapeutic consequences the patient may benefit from.

PO=4R1-87 S . k o b a y a s h i , Y . s u z u k i , S.yasuda , T . n o t o , H . k i j i m a , M. i d e . Dep. Radiology,surgery,pathology and Int.med. Tokai univ. Isehara, Japan Tc-99m-HMPAO LABELLED GRANULOCYTES SCAN IN COLORECTAL CARCINOMA USING SPECT. Recent observations imply a more important role for granulocyte in dfence against tumor cells. In this study, we investigate the ability of granulocyte to accumulate in colorectal carcinoma with Tc-99m-HMPAO labelled granulocytes using whole body scan and SPECT. Patients and method: 30 patients with surgical proven colorectal carcinoma were studied. The granulocytes were labelled using a modification of the method described by Solanki et al. Whole body images were obtained at 3 hr after injection of labelled granulocytes, and then SPECT imaging of pelvis including the upper abdomen was done. Results: The SPECT showed positive in 29/30; if: greater than bone m a r r o w activity of the lumbar spine(BMA), 5: equal to BMA, 13: lesser than BMA. The whole body images showed positive in 19/30. Conclusion: Although further evaluation should be necessary, the result of this study suggests that the labelled granulocytes accumulation in malignant tumor is more frequent than previous thought in literature. We propose the accumulation of labelled granulocytes in colorectal carcinoma may be related to antitumor effect of granulocyte, and also scintigrafic study with labelled granulocytes is useful tool of evaluating for its immunological role in vivo.

680

CLINICAL EVALUATION OF FDG-PET STUDIES IN THE STAGING OF LUNG TUMORS The feasibility as well as potential applications of positron emission tomography (PET) with F-18-deoxyglucose (FDG) of the thorax has been established in previous studies. The promising results encouraged a clinical study to evaluate the benefit of diagnostic PET studies in comparison to the surgical results. 65 patients were studied with PET in the course of diagnostic evaluation of newly detected, indeterminate lung tumors prior to invasive staging. Histology was confirmed by biopsy in everey patient. Surgical resection was performed in 25 patients. Tclassification for TNM staging was compared between the conventional diagnostic methods, PET and invasive staging. The final T-stage was determined by bronchoscopy (49%), surgery (38%), thoracoscopy (2%) or clinically (11%). PET confirmed the T-stage of the conventional staging in 56%, decreased T in 2 2 % and increased T in 2 2 % of the patients. The PET T-stage agreed in 9 8 % with the invasively confirmed T value. Since all leasions to be studied had to be larger than 2 cm in diameter, no T1 condition was found. 3 3 % were T4, 16% T3, 3 3 % T2 and 18% TO. The analysis of the 14 patients in which PET decreased T shows that in the majority, 10 cases, PET downstaged to a benigne leasion, most commonly from T3 to TO. In comparison we found that in the 14 patients with increased T, 9 increases were due to upgrading to a T4 tumor. In the evaluation of tumors PET correctly identified 63 of the 65 patients by classifying 53 of 54 malignant and 10 of 11 benigne leasions as such. We can conclude that FDG-PET studies are of great clinical value for the staging of ambiguous lung tumors.

PO-4R1-88 L. K o s t a k o g l u , H. K a l a i g i a n , H. Abdel-Dayem~ S.D,J,Yeh, D. N y e d v w i e c k i , S,M. L a r s o n . M e m o r i a l S l o a n - K e t t e r i n g C a n c e r Center, New York, NY. SEMIOUANTITATIVE GA-67 SPELT TO DIFFERENTIATE FIBROSIS FROM RECURRENCE IN TREATED MEDIASTINAL HODGKIN'S DISEASE (H,D).: CORRELATION WITH fiT & BIOPSY. CT is n o t a r e l i a b l e m o d a l i t y f o r d i f f e r e n t i a t i n g m e d i a s t i n a l f i b r o s i s f r o m r e c u r r e n t H.D in p o s t t h e r a p y p a t i e n t s (pts), O c c a s i o n a l l y . Ga-67 SPELT studies f o r t h e m e d i a s t i n u m a r e d i f f i c u l t to v i s u a l l y i n t e r p r e t f o l l o w i n g t r e a t m e n t . In o r d e r to differentiate f i b r o s i s f r o m a c t i v e t u m o r (tin) we u s e d a s e m i - q u a n t i t a t i v e t e c h n i q u e o n SPELT to q u a n t i t a t e the a c t i v i t y i n tm v o l u m e a n d c o n t r a l a t e r a l site as a reference for comparison, P r e v i o u s l y t r e a t e d 29 p a t i e n t s w i t h m e d i a s t i n a l H.D u n d e r w e n t SPECT 48 h r s f o l l o w i n g t h e a d m i n i s t r a t i o n of i0 mCi o f Ga-67 c i t r a t e . All pts h a d c o n c u r r e n t h i s t o p a t h o l o g i c a n d CT c o r r e l a t i o n s . 6 pts h a d f i b r o s i s a n d 23 h a d v i a b l e H.D o n tissue d i a g n o s i s . CT r e s u l t s w e r e e q u i v o c a l i n all 6 pts w i t h f i b r o s i s a n d in 8 pts w i t h a c t i v e tm. SPELT i m a g e s could n o t d i f f e r e n t i a t e f i b r o s i s f r o m a c t i v e tm i n 9 pts, ( i n c l u d i n g the pts w i t h f i b r o s i s ) . Reconstructed and attenuation corrected transverse s e c t i o n s w e r e u s e d t o d r a w r e g i o n s of i n t e r e s t w i t h i n tm v o l u m e and background ( b k g ) o n c o n s e c u t i v e slices w h e r e the bkg w a s t a k e n in c o n t r a l a t e r a I n o r m a l l u n g fields o n the s a m e slices t a k e n f o r tin. Total n u m b e r of pixels (pix) a n d c o u n t s (cts) w e r e o b t a i n e d . T h e r a t i o b e t w e e n a v e r a g e c t s / p i x o v e r slices in tm v o l u m e a n d b k g w a s c o m p u t e d . There w a s s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e b e t w e e n r a t i o in v i a b l e tm v o l u m e a n d f i b r o s i s , The m e a n r a t i o s w e r e 4.61 +_ 1,62 a n d 1.65 +_ 0,08 in v i a b l e t m a n d f i b r o s i s , r e s p e c t i v e l y . (p = 0.0001 ) In c o n c l u s i o n , t h e r a t i o b e t w e e n c t s / p i x i n tm v o l u m e a n d bkg is of g r e a t h e l p i n d i s t i n g u i s h i n g b e t w e e n tm a n d f i b r o s i s , t h u s , q u a n t i t a t i v e SPELT s u r p a s s e s o t h e r m o d a l i t i e s in d i f f e r e n t i a t i n g f i b r o s i s f r o m v i a b l e tm.

W e d n e s d a y , 4 S e p t e m b e r 1991

PO-4R1-89 S.Lastoria,E.Vergara,L.Castelli,B.Pecori,C.Carace, E.Sec camani*,C.Bonino*,M.Salvatore Nucl.Med. Dept.University of Napoli and Nucl.Med.Dept.of Cancer Istitute Napoli,*Sorin Bio.Saluggia ITALIA HUMAN GLIOMA wITH LABELED BC2 MONOCLONAL ANTIBODY Current diagnostic and therapeutic modalities for mal! gnant human gliomas are largely non specific.This study evaluates the localization and imaging of BC2 MoAb,wich cross with a human glioma-associated extracellular pro tein:tenascin(TN).26 pts with brain masses(21 with gli£ ma,4 with metastatic melanoma and 1 with meningioma)were studied.14 pts received from 0.6-i mg of BC2 labeled with 131-I(from 2.99 to 6.42 mCi).12 pts received 1 mg of BC2 labeled with 99mTc (range 11-16 mCi).Plasma half lives for 131-I BC2 ranged 2.5-4.5 h for the first com ponent and 40-60 h for the second component. Cumulative 131-I urinary excretion ranged from 20!10% at 24 h to 60~18% of ID at 96 h.Plasma half life for 99mTc BC2 was 5~0.5 h.With 131-I BC2 9 glioma were imaged,while 2 astrocitoma grade II and 1 meningioma resulted negative. One out of two melanoma brain mets.was visualizated. Tu mor/nontumor ratios ranged from 3 to 7.5:1 and it was i:i in negative cases. The sensivity using 99mTc BC2 was 90% in glioma while in two pts with melanoma 6/8 lesions were correcty identified(75%).We demonstrated that tumor uptake had a s~rong positive correlation with tumor size histologic grade of differentiation and tumor blood flow supply as demonstrated with SPECT using 99mTc-EPAO.These results demonstrated:a)BC2 uptake in gliomas related to tumor degree;b)the % of BC2 tumo-bound allows a succes full gamma imaging;c)a significant gradient in the loca lization between tumor and normal brain rapresent a key factor for specific therapy.

PO-4R1-91 S . R . Li, I . V i r g o l i n i , E.Wandl, H . S i n z i n g e r Depts of Nuclear Medicine and Clinical Radiobiology, University Clinic for R a d i o t h e r a p y , U n i v e r s i t y Vienna, A u s t r i a . EFFECT OF ASPIRIN ON PROST~GLANDIN RECEPTORS IN CULTURED HYPERNEPHROMA BEFORE AND AFTER IRRADIATION

(PG) CELLS

S p e c i f i c PGEI, E 2 and 12 b i n d i n g s i t e s a n d s t i m u l a t i o n of c A M P by t h e s e c o m p o u n d s h a v e b e e n i n v e s t i g a t e d in c u l t u r e d h u m a n h y p e r n e p h r o m a c e l l s d e r i v e d f r o m 17 p a t i e n t s a g e d 60±12 a. E a c h cell line w a s d e v i d e d i n t o 4 groups: c o n t r o l group, a s p i r i n - t r e a t e d g r o u p (0.5 m g / l O 6 c e l l s / m l m e d i u m for 24 h o u r s ) , control group irradiated (CO60-irradiation; d o s e r a t e of 1.0 G y / m i n for ii min) and aspirin-treated group irradiated. Scatchard a n a l y s i s of t h e b i n d i n g d a t a r e v e a l e d a v e r y l o w n u m b e r of PGEI, P G E 2 as w e l l as PGI 2 h i g h affinity binding sites-and an i n s i g n i f i c a n t i n c r e a s e in c A M P - f o r m a t i o n a f t e r s t i m u l a t i o n w i t h t h e s e c o m p o u n d s in the c o n t r o l group. However, a significantly (p
Th~sstay is supportedby the OnkoLogie-Forschungsfo~of the Universityof Vienna.

PO-4R1-90 J.M. Le Doussol A. Chetonneuu, A. C-ruuz-Guyon, E. Guutherot, M. Murtin, G. Anfossi, P.A. Lehur, J.F. Ch~ol, M. Delooge, und J. Borbet. Immunotech S.A. Morseille, and Centre Ren6 C-uuducheou, Nantes, Fronce. Colorectol concer imuging in human with i n - l | ] lubeled low molecular weight bivalent hopten ond duul specificity monoclonQI ontibody conjugute. A radiolabeled bivalent hapten and a dual specificity antibody conjugate have been used for tumor imaging in primary coiorectal carcinoma patients, The bivalent hapten was synthesized by reacting DTPA dianhydrJde with tyrosyldysine and was labeled with In] I ] . The dual specificity conjugate was prepared by coupling the Fab' fragment of an anti-CEA monoclonal IgG] (CIS Bio International, France) to the maleimidederivatized Fab fragment of an anti-(DTPA-Indium) monoctonal IgG]. All products were tested for sterility, pyrogens and toxicity. ~ight patients, who gave informed consent, received 1 to 5 mg of conjLJgate by iv, infusion, followed, 2 to 8 days later, by an i.v. injection of labeled hapten (222 MBq, 2 nmol) No adverse reaction was observed, Planar and tomographic images were recorded 5 and 24 hr after tracer injection, Surgery was performed at 48 hr, Pharmacokinetics and biodistribution were monitored, With 7 out of the 8 patients, good were contrast images allowing tumor localization obtained 24 hr, and with 4 of them as soon as 5 hr, after tracer injection, Surgery and imaging of surgical specimens confirmed tumor localization Tumor uptake and tumor to normal organ contrasts depended primarily on conjugate dose and tumor size. Maximum tumor uptake (0,06 % of injected dose per g) and tumor to normal tissue ratios (9,0 for colon, 15 for liver) were obtained after injection of 5 mg of conjugate and a delay of 4days before tracer injection, Thus the technique provides as major potential advantages over indium-labeled antibody fragments faster clearance of excess radioisotope and higher tumor to liver contrast,

PO-4R1-92 P.Lind_, P.Lechner, P.K61tringer, M.Klimpffmger, O.Eber, Barmherzige Briider Eggenberg Hospital, Nuclear Medicine, Austria ANTI-CEA IMMUNOSCINTIGRAPHY (Tc-99m MAb BW 431/26) AND SERUM CEA-LEVELS IN COLORECTAL CANCER CARE With the introduction of Tc-99m labeled monoclonal antibodies against eareinoembryonic antigen (CEA), a clinically relevant progress can be expected in the diagnosis of colorectal carcinomas by immunoscintigraphy (IS). This study comprises a total of 161 patients (primary colorectal carcinomas [PCC], occult neoplasms and suspected colorectal recurrences [CR]), in whom IS with Tc99m MAb BW 431/26 was performed. Whole body scans were done 5 1/2 hours and SPECT of the abdominal region 6 and 24 h post injection of 1100 MBq Tc-99m labeled MAb. In the course of primary tumor identification (n=75), almost all surgically verified carcinomas (n=53) were confmned and correctly localized by IS (sensitivity 94%, specificity 91%). In the diagnosis of recurrences (n=86), IS showed a sensitivity of 95% and a specificity of 85%. Especially in patients in whom transmission computed tomography (TCT) failed to differentiate clearly between scar and recurrence, IS was the method of choice to clarify the problem. Human anti-mouse antibodies were found in 29% (80% predominantly antiisotypic, 20% antiidiotypic). In contrast to anti-CEA IS, the results of serum CEA levels were rather disappointing. From the 53 surgically verified primary colorectal carcinomas serum CEA was elevated in only 25 cases and in the normal range in 28 cases. Serum CEA in patients with colorectal recurrences was elevated in only 21 out of 38 patients. According to our clinical experience with this Tc-99m labeled monoclonal antibody, anti-CEA IS plays a pre-eminent role in the exclusion or identification of colorectal recurrences. Therefore, in postoperative colorectal cancer care, IS should be performed in cases with unclear TCT, even if the serum CEA level is in the normal range.

681

Wednesday, 4 September 1991

PO-4R1-93

PO-4R1-94

K.Kukulski r J.Liniecki, D.Brykalski, et al. Department of Nuclear Medicine, Medical University of Lodz, Czechoslowacka 8/10, Lodz 92-216

J. Lurnbroso, F. Montravers, M. Hicard, M. Di Paola, R. Di Paola, C. Parmentier INSERM U66 and Institut Gustave ROUSSY, F-94805 , Villejuif , FRANCE

LYMPHOMA STAGING USING z6wz~-CISDICHLORODIMETHIONIN PLATINUM (PtCl=Meth=) AS AN 0NCOPHILIC AGENT

DIGITAL SUPERIMPOSITION OF CT AND POSITIVE TUMOUR TRACERS SPECT: PHANTOM STUDY AND CLINICAL APPLICATIONS.

• 6~yb-PtCl=Meth= was used for detection and staging of malignant lymphoma (Hodgkin's and non Hodgkin). This compound has properties similar to those of 6~Ga citrate, however, due to dominant urinary elimination detection of the loci below the diaphram becomes more accurate. Scintigraphy was made 24h after intravenous injection of 60 - 70 MBq of x=~Yb-PtCl=Meth=. Seventeen patients were studied prior to theraphy, 18 with the active disease after commencing radio and/or chemotherapy, 3 patients under clinical remission, 8 patients with the certain or suspicion of the recurrent disease. In all, 458 sites diseased and free of the lymphoma loci, were studied. Sensitivity of the test in patients investigated prior and after initiation of therapy amounted to 89 and 78 %, respectively. Predictive .value of the positive test, correspondingly, was 83 and 74 % Specificity was similar in both groups of ab. 83 %. Therapy reduces uptake of the radiopharmaceutical in the diseased loci. Patients with verified remission were scintigraphically free of the active foci. In patients with recurrence of malignant lymphoma the scintigraphy confirmed presence of diseased loci. In 2 patients suspected of the recurrence active, verified foci were identified. The results strongly suggest that x~gYbPtClmMeth= may be successfully used for staging, monitoring of the therapy and for early detection of recurrence of malignant lymphoma.

An aCcurate interpretation of functional data provided by emission tomography (SPECT) needs a confrontation with anatomical data provided by X-ray computed tomography (CT). Digital superimposition of SPECT (obtained with modern garama camera) and CT data was evaluated in a phantom and then applied to patients. We inserted either capillary tubes or larger objects in a plexiglas phantom (abdomen like) filled with water. The use of 99mTc and 131I solutions at various concentrations allowed to simulate hot structures and background. Ten pts were studied: 6 had a relapsing pheochromocytoma (using 131I or 123I-mIBG); 3 Hodgkin's disease (using 67Ga-citrate) and i suspicion of an ovarian cancer (using lllIn-MoAb anti-CA 125). Internal anatomical landmarks, obtained by the injection of 99mTc-HMDP or 99mTc-colloid and, when not possible, skin landmarks, were used to identify the level of each SPECT transax~al slice. Both SPECT and CT slices were transferred on a mini computer connected to an image processor. An affine transform allowed translation, rotation and scale correction. Slice of each modality was coded in a primary colour and then superimposed Superimposition of phantom slices allowed to check the absence of distortion for pinpoint structures as well as for larger ones. For suspected tumour sites, superimposition of pts' slices allowed to check matching between positive functional and morphological data in 5 cases; to localize a positive functional abnormality without morphological correspondence in 2 cases and to rule out any tracer uptake by a residual mass seen on CT. in 2 cases. In one case, the technique failed due to a very low 131I-mIBG tumour uptake. The superimposition decreases both false positives in SPECT and false negatives or false positives in CT.

PO-4R1-95

PO-4R1-96

H. Macapinlac, V. Rusch, R. Heelan, E. Kramer, I, Ginsburg, K. Sullivan, D. Salk. P. Abrams. and S. Larson, Memorial Sloan-Kettering Cancer Center, New York, NY USA

L. Massuger, R. Claessens, C. TiDben, Ch. Schijf, P. Kenemans, F. Corstens. University Hospital Nijmegen, The Netherlands.

THE ROLE 0F Tc-99mNR-LU-10 ANTIBODY,IMAGING IN NEWLY DIAGNOSED NON-SMALL CELL LUNG CANCER The purpose of this study is to evaluate the contribution of this antibody imaging t e c h n i q u e in preoperative staging of patients with n e w l y diagnosed non-small cell lung cancer. NR-LU-10 is a m u r i n e IgGZb antibody labeled with Tc-99m w h i c h r e c o g n i z e s a 40 kD glycoprotein expressed in small and n o n - s m a l l cell l u n g cancers (NeoRx corporation). The antibody was infused I.V, (25-30 mCi in 3-5 rain,) followed by whole body and SPECT imaging 14-17 h r s later, CT of the thorax to the l e v e l of the adrenals and e t h e r essential i m a g i n g modalities w e r e done w i t h i n 2 w e e k s of the antibody study, Antibody images w e r e reviewed with full knowledge of the patients clinical status, Reexamination of CT and other modalities were done if an occult metastases was seen, All the patients u n d e r w e n t mediastinoscopy a n d / o r thoracotomy for histopathologic confirmation. Twenty one patients w e r e g i v e n the antibody infusion with no notable immediate adverse effects, The antibody study detected 20 primary tumor sites and one true n e g a t i v e site w h i c h was i n f l a m m a t o r y but read as tumor on CT,.The antibody imaging accurately restaged 2 patients from NI to N2 and therefore determined the inoperability of these patients. Overall, the antibody study together with CT accurately staged 83 % of all the patients. We conclude that the NR-LU-10-Tc99m antibody scan is a useful procedure to complement CT in preoperative evaluation of patients with non-small cell lung CA.

DETECTION OF OVARIAN CANCER USING Tc-99m-LABELED OV-TL 3 Fab'. The murine monoclonal antibody (MAb) OV-TL 3 recognizes a cell surface antigenic determinant (CA3) present on more than 90% of ovarian carcinomas. With In-lll-labeled F(ab')2 fragments of OV-TL 3 successful imaging was obtained in patients with ovarian cancer. However, using this preparation the scintigraphic study of an individual patient took 48-72 hr. Because of the faster biokinetics, the Fab' fragment of OV-TL 3 was chosen instead and labeled with Tc-99m using Dglucarate as a transfer ligand. So far, ii patients underwent iramunoscintigraphy (IS) after i.v. administration of 740 MBq Tc-99mlabeled OV-TL 3 Fab' (i mg). Is (planar and SPECT) was performed up to 30 hr postinfusion. Blood samples were taken regularly and in selected patients urine and feces were collected throughout the whole study. In all patients X-ray computed tomography (CT) and ultrasonography ( U S ) had been performed. Surgery was performed on all patients between 40 and 50 hr postinfusion. In all (tumor and non-tumor) tissue samples, obtained at surgery~ the amount of Tc-99m was measured. No adverse reactions were observed in any of the patients. Blood clearance could be represented by a biexponential model with halflife values of 0.5 and 9.6 hr. Within 24 hr excretion in urine (n=5) was 44% ID, whereas feces activity (n=l) amounted to 3.5% ID. Mean tumor (primary localizations) and muscle uptake were 2.0 ± 0.5 and 0.5 ± 0.2% ID/kg, respectively. In i patient an CA3 negative ovarian malignancy showed no elevated uptake of Tc-99m. In 8 out of the remaining i0 patients with CA3 positive ovarian carcinomas, tumor localizations were detected with IS. Of 25 distinct tumor deposits larger than 1 cm in diameter found at operation 48% were detected with IS, while CT and US detected 44 and 40%, respectively. IS with Ts-99m-OV-TL 3 Fab' is less time consuming than IS with In-III-OV-TL 3 F(ab')2 , while the results so far seem similar.

682

Wednesday,

4 September

1991

PO-4R1-97

PO-4R1-98

SP M011er1, M Paas 1, V Budach 2, N Konietzko 3, W Alberti 4, C Reiners 1.

J Muz, R Mathog, S Hamlet, R Farris. Departments of Radiology and Otolaryngology, Harper Hospital and Wayne State University, School of Medicine, Detroit MI USA.

Nuclear Medicine 1, Radiation Therapy2, University Essen, Ruhrlandklinik Heidhausen 3, Alfried Krupp Hospital 4 Essen, FRG

ROC ANALYSIS OF TUMOR DETECTABILITY WITH PLANAR IMAGING AN D SPECT USING Tc-99m MIBIAN D TI-201 IN BRONCHIAL CARCINOMA. TI-201 scintigraphy is established for tumor detection and the assessment of viability and response to therapy. Recently Tc-99m methoxy isobutylisonitrile (MIBI) has been suggested as an alternative in thyroid and bronchial carcinoma. It holds promise for better image quality due to lower scatter and attenuation and better resolution and counting statistics. For a quantitative assessment of tumor detectability with TI-201 and MIBI, we conducted a prospective study comparing the detectability of bronchial carcinoma in S PECT and planar imaging using correlated ROC anaysis. We studied 27 bronchial carcinoma patients and 7 controls with coronary artery disease. We injected 75 MBq TI-201 and acquired planar scans (5 minutes/image ap, pa, lateral views) starting 20 min. p.i., followed by a SPECTstudy (20 min. acquisition) of the thorax. Then 350 MBq MIBI were injected and 600k counts planar and 20 min. SPECTscans acquired in the same patient position. The images were independently viewed by 2 observers in a 3-D volume display; the display window was freely adiustable by the observer. Planar images were displayed on a regular viewing box. Each lung was divided into an apical, middle, and caudal region, and each region was independently rated for the likelihood of tumoron a scale from 0 to 5. True positive regions (n=27) were contimed by biopsy or X-ray; a region was considered true negative if it remained tumor free for at least 6 months after the study (n=126). The fitting of ROC curves and statistical tests were carried out with CE Metz's CORROC2program. Neither the bivariate %2-test (compares the ROC curve parameters), the area test (compares detectability), or the comparison of the true positive fraction (TPF) at a false positive rate (FPF) of 5% showed significant differences betwee n MIBI and TI-201 (p>0.1) for either planar or SPECT imaging or between the 2 observers. SPECTwas significantly better than planar imaging; at a FPF of 5% the TPF for planar vs SPECT imaging was 69% vs 84% and 66% vs 79% for TI-201 (p<0.05) and for MIB153% vs 83% and 54% vs 82% (p<0.01) for observer MP and SPM. Despite the theoretically superior physical imaging characteristics of MIBI the tumor detectability in bronchial carcinoma is equivalent for TI-201. SPECT is superior to planar imaging for tumor detection in the chest and should also be preferred for patients with other tumors, such as e.g. thyroid carcinoma.

SCINTIGRAPHIC ASSESSMENT OF SWALLOWING FUNCTION IN HEAD AND NECK CANCER PATIENTS. The purpose of this presentation is to demonstrate application of scintigraphic criteria, such as oral transit time (OTT), pharyngeal transit time (PTT) and tracheopulmonary aspiration (TPA) for assessment of swallowing function in patients (pts) with head and neck cancer (HNC). Studies are obtained with a scintillation camera and a computer. A dose of 2.5 mCi (92 MBq) Tc-99m sulfur colloid mixed with I0 ml of water is given to the patient to swallow and dynamic and static images are obtained. The OTT and PTT are obtained from time activity curves derived from the oral and pharyngeal regions. In pts who aspirate, the percentage of aspiration (PA) is calculated using the formula: PA = (RA x 100)/TC, in which RA represents the counts in the region of aspiration and TC the total counts. Total body radiation to the patient was estimated to be 0.043 rads. Of the 193 HNC pts studied with scintigraphy, 80 pts (41%) revealed evidence of TPA. In the group of 113 HNC pts without tracheostomy, 31 (27%) revealed TPA. Of the 80 pts with HNC and tracheostomy, 49 (61%) demonstrated TPA. Our studies revealed that pts with tracheostomy aspirate more often and in larger quantities as compared to HNC pts without tracheostomy. In view of these findings, we propose that a clinical protocol be established to deal with the TPA problem. The pts who aspirate should be fed carefully and have periodic assessment of swallowing function using scintigraphy. In conclusion, the scintigraphic technique is reliable for the assessment of swallowing function and the detection and quantification of tracheopulmonary aspiration. 91jmenmc, 02/21/1991,

PO-4R1-99 CE l~al, E. Surwit, HH Gallion, UY Ryo, JW Keyes Jr., TL Swan Southern Illinois University School of Medicine and The Mulitcenter Trial Group, Springfield, Illinois, USA nlIn-CYT-103 IMMUNOSCINTIGRAPHY IN OVARIAN CARCINOMA: PERFORMANCE COMPARISON WITH CT AND SURGERY PURPOSE: This study was designed to evaluate the safety and imaging performance of lllIn-CYT-103 in preoperative patients with primary and recurrent ovarian adenocarcinoma. METHODS: The monoclonal antibody B72.3 was site-specifically labeled with n l I n using the linker-chelator GYK-DTPA (CYT-103). 108 patients were infused with 1 mg of the antibody CYT-103 labeled with 4 - 5 mCi of n l I n under a protocol approved by an institutional review board. Patients underwent planar imaging of the chest, abdomen, and pelvis and SPECT imaging of the abdomen and the pelvis within 7 days of the injection. Patients also underwent CT of the abdomen and the pelvis. The patients then underwent surgery to correlate with the antibody and CT scan results. RESULTS: For patients imaged by both modalities, antibody imaging demonstrated a higher sensitivity (69% versus 44%) and lower specificity, (57% versus 79%) than CT imaging. Antibody imaging correctly detected tumor in 19 patients with negative CT scans. However, CT scans were positive in 2 patients with negative antibody images. Occult ovarian carcinoma lesions, including carcinomatosis, were detected in 28% of patients with surgically confirmed disease. Overall, monoclonal antibody scanning was felt to have a beneficial impact in 28% of patients studied. 32% of the patients evaluated developed a positive HAMA titer at 4 weeks postinfusion. One patient had minor adverse effects attributed to the antibody infusion. CONCLUSION: The results of this study indicate that this monoclonal antibody can be safely administered and that this agent can contribute beneficially to the management of patients with ovarian carcinoma. By detecting occult tumor, immunoscintigraphy can provide important diagnostic information to compliment the findings of other presurgical diagnostic and staging studies.

14:12:13, p.1

PO-4R1-100 L.P~vic~, Z. T 6 t h Bagi, L. Alm~si, E. Ambrus, Gy. Szab6, and L. Csernay, Albert Szent-GySrgyl Medical University, Szeged, and Semmelwels University of Medicine, B u d a p e s t , H u n g a r y CEREBRAL PERFUSION RESPONSE OF INTRAARTERIAL CHEMOTHERAPY OF HEAD AND NECK TUMOURS. A combination of Cisplatin and Epirublcin was administered t h r o u g h the external carotid a r t e r y system according to a s t a n d a r d protocol as preoperative or palliative therapy in 14 oral c a n c e r patients. With the aim of clarifying the subacute side-effects of this chemotherapy on the intracerebral circulation, rCBF SPECT investigations with 9 9 m T c - H M P A O were performed b e f o r e a n d after the c y t o s t a t i c treatment. The interval b e t w e e n SPECT studies was 24 (SD_+I2) days. In concordance with the neurological condition, visual a s s e s s m e n t of the r C B F S P E C T reconstructed transversal slices revealed no perfusio~ abnormalities and no c h a n g e s on the follow-up. With the exception of 2 areas, no significant changes were found in the side activity ratios in 22 regions of e a c h h e m i s p h e r e (unpaired t-test). In the orbitofrontal area, overlapping with the pharingeal region was suspected as the cause of the detected alterations. In the l e f t - s i d e - t r e a t e d patients, in the superior occipital area the presumed perfuslon abnormality w a s n o t e d only with w e a k statistical significance. It w a s concluded that this highly effective combination of c y t o s t a t i c s administered perfectly through the external carotid artery system causes no serious disturbances in the cerebral circulation in oral c a n c e r cases.

683

Wednesday, 4 September 1991

PO-4R1-101

PO-4R1-102

P. Peltier, J.P. Dutin, J.F. Chatal Clinical Research Network (Nantes, Villejuif, Saclay, France). IS OC 125-INIII IF~UNOSCINTIGRAPHY DIAGNOSING OVARLAN C A N C E R ~ C E S

and the Rennes,

INSERM Reims,

(IS) USF~JL

IN

?

The aim of this study was to use Bayes theorem to evalutate the utility of In-lll 0C 125 - IS in the diagnostic strategy of ovarian adenocarcinoma (Or-CA) recurrences. A prospective IS study was performed in 70 patients with OV-CA previously treated. IS (70 times), US (54 times) and CT (36 times) were performedwithin 4 weeks. Imaging accuracy was confirmed by cytohistological methods (63%) and clinical follow-up (37%). Sensitivity (SE), specificity (SP), negative predictive value (NPV) and positive predictive value (PFV) using a 0.50 pretest probability are shown in the following table :

SE SP NPV PPV

US

CT

IS

US + C T

US + ~

0,34 0,75 0,53 0,58

0,57 0,87 0.61 0,63

0,87 0,75 0,85 0,78

0,64 0,70

0,87 0,82

Cf + ~ US + C T + IS

0,90 0,86

0,91 0,89

In-lll OC 125 - IS was the most accurate procedure ($E, SP). When pretest probability is 0.50, a negative US and/or CT cannot exclude recurrences (NPV < 0.80). However, when IS is negative, the probability of a patient being recurrence-free is high (NPV > 0.80). CT/US and IS must be positive to have a high probability of recurrence (PPV > 0.80). In-lll OC 125 - IS should be included in the diagnostic strategy of OV-CA recurrence. The information provided by this procedure is critical for comparative diagrlosis with US and CT results.

PO-4R1-103 V. Rufini, M.S. Daidone, L. T e o f i l i * , G . N i c o l e t t i * , G. Leone* and L. Troncone. I s t i t u t i di Medicina Nuclea re e Semeiotica Medica*, Universit~ Cattolica del Sacro Cuore, Roma, I t a l y AN UNUSUAL ASSOCIATION OF NEUROFIBROMATOSIS (NF) AND NEUROBLASTOMA (NB) INVESTIGATED WITH 131-I-MIBG. Only a few cases of NF, a genetic disorder that affects neural crest derived c e l l s , have been investigated with *I-MIBG so f a r , mainly to detect a possible associated pheo. We here report on an unusual case of NF associated with ganglioNB studied with 131-I-MIBG scintigraphy. A 22 year old male came to our observation exhibiting a pathologic fracture of the l e f t femur. He had no family history of NF, a considerable facial deformity,multiple neurofibromas and "caf~ au l a i t " spots on the skin.Blood pressure was normal. The work-up showed: increase in the urinary excretion of catecholamines,VMA and HVA; a l y t i c lesion of the l e f t hemimandible, an extrapulmonary mass adherent to the posterior thoracic wall, a l e f t adrenal mass, maxillary and mandibular neoformations and a voluminous brain mass.Scintigraphy with 131-I-MIBG (37 MBq i . v . and whole body scan at 24 and 48 hr) showed focal areas of pathologic a c t i v i t y in the brain, maxillary and mandibular region, posterior thoracic wall and both femurs as well as in the l e f t adrenal mass. Pathological diagnosis of the removed adrenal mass was ganglioNB with exuberant neurofibromatous component. Biopsy of the subpleural mass as well as of the l e f t femoral lesion revealed the presence of neurofibromatous tissue. The case presented appears of qreat i n t e r e s t both because i t demonstrates 131-I-MIBG uptake in tumora] lesions of NF and i t is to our knowledge the f i r s t case of N8 associated with NF studied with *I-MIBG.

684

M. Ra.it~, O. Esik*, L. C s e r n a y Albert S z e n t - G y 6 r g y i Medical University, Depts. of Nuclear Medicine and Radiology, S z e g e d (*present workplace: Uzsoki Hospital, Dept. of Oncoradiology, Budapest), H u n g a r y VALUE OF INTERNAL MAMMARY NODE SCINTIGRAPHY IN RELAPSED BREAST CANCER

AND AXILLARY LYMPH LOCALLY/REGIONALLY

Aim of the study: Is lymph n o d e scintigraphy of a n y importance in confirming the diagnosis of locally/regionally relapsed breast cancer and planning the s u b s e q u e n t t h e r a p y ? Method: Internal mammary (IM) and axillary (Ax) lymph node scintigraphy was performed with 99mTc-HSAnanocolldid (Nanocol SOLCO) in 183 c o n s e c u t i v e b r e a s t c a n c e r patients with a relapse d e v e l o p e d by a suspected lymphatic turnout spread. Patie/l~ grouD~i Local r e c u r r e n c e (LR) 26, local/regional r e c u r r e n c e (LRR) 57, solitary s t e r n u m m e t a s t a s i s (SSM) 18, bilateral m e t a s t a t i c b r e a s t c a n c e r (BMBC) 2. Results: Ipsilateral IM involvement w a s f o u n d in 15/26 of LR, 4 2 / 5 7 of LRR, 15/18 of S S M and 2/2 of B M B C patients, and ipsilateral Ax involvement in 14/26 of LR, 3 2 / 5 7 of LRR, 13/18 of S S M and 2/2 of B M B C patients . . . . . . . . . . . . (i) T h e high r a t e of IM and Ax lymph n o d e involvement s e e m s to confirm the t h e o r y of the lymphatic origin of the a b o v e m e n t i o n e d entities. (2) T h e m e t h o d c a n be a useful diagnostic tool, w h e n local/reglonal r e c u r r e n c e is suspected. (3) By d e m o n s t r a t i n g the actual extent of the disease, the m e t h o d c a n help in planning of the s u b s e q u e n t therapy.

PO-4R1-104 S.K.Shuklal, 2, H.Xie 3, Zh.Yao 3, K.Schom~cker4,C.Cipriani I

G.Argir61, F.Boccardil; 1)Nucl.Med.,Osp.S.Eugenio,Roma; 2)Ist. Cromatografia,CNR,Roma; 3)Shanghai Inst. Cell Biol. China; 4) Klin.Poliklin.Nuklearmed.,KSln Univ.,Germany EARLY DETECTION AND THERAPY OF LIVER CANCER RESPECTIVELY WITH PURE TUMOR-SPECIFIC Ga-67 AND Y-90 AS SIMPLE COMPLEX OR AS ANTIHEPATOMA ANTIBODY,HEPAMA-I,LABELED SPECIES Liver cancer incidence is high in Asian and African countries. In China it is known as "black cancer" due to large number of victims caused every year. Recently the Shanghai Institute of Cell Biolop~v produced antihepatoma antibody fragment, hepama-l, and labeled it with 1-131 which showed little tumor affinity and high healthy organ concentration of the radionuclide in human hepatoma xenografts in nude mice and also in hepatoma patients due to the instability of the 1-131-hepama-l. In Rome we have produced chromatographically and electrophoretically pure hepatoma-affine Ga-67 and Y-90 species in solution. In collaboration with the Shanghai group of researchers, we studied simultaneously, in Rome as well as in Shanghai, the affinity of Ga-67 and Y-90, as simple complex in solution and as labeled hepama-l, for human hepatoma cells in vitro and for human hepatoma xenografts in nude mice. In both cases the radionuelides bound strongly to the hepatoma cells and hepatoma in nude mice, and remained so until the decay of the radionuclide. This permitted the followup studies of the fate of hepatoma for about 9 days p.i. of Ga-67.With repeated injections of Y-90,as pure hepatoma-specifie species in solution, we obtained regression of hepatoma of diameter less than 1 cm, while the bigger ones became necrotic. The antitumor activity of Y-gO-hepama-i is similar to that of simple hepatoma-affine Y-90 complex solution.

Wednesday, 4 September 1991

PO-4R1-105

PO-4R1-106

LG. Strauss, A. Dimitrakopoulou, u. Haberkorn, H. Ostertag, F. Helus, W.J. Lorenz. German cancer Researchcenter, Heidelberg, FRG.

TL Swan, CE Neal, J H Texter, RL Ellis, J G Katterhagen Southern Illinois University School of Medicine, Springfield, Illinois, USA

PET STUDIES WITH F-18-DEOXYGLUCOSE (FDG) IN PATIENTS WITH METASTATICMELANOMA PRIORAND AFTERTHERAPY Several chemotherapeutic Protocols are used for the treatment Of patients with metastatic melanomas, we performed PET in these patients in order to quantify the metabolic activity in metastases Prior and after theraPy. The evaluation includes 12 PET studies in 6 Patients. CT examinations preceeded PET in each patient to determine the target area. PET studies were performed with FDG (370-444 MBq), followed by sequential imaging for 60 minutes, standardized uptake values (SUV) were calculated from the iteratively reconstructed cross sections using a ROl-technique. The FDG uptake in lymph node metastases was 2,1-13.1 SUV prior to therapy. Lower values were observed in bone metastases (1.3 SUV),while the FDG-Uptake was 2.5-3.0 SUV in metastases of the adrenal gland. Comparable results were obtained in liver metastases (2.5-3.4 SUV).FollOw-Up studies after chemotherapy with fotemustin (200 rag, 30 min infusion) showed a 3 % decrease in tumor metabolism as early as 90 minutes after chemotheraPy. The decrease in FDG uptake was 9 % and 26 % one and two days after therapy and remained constant for one week. The median decrease in FDG uptake following chemotheraPy was 27.5 %. Our results show, that PET with FDG can be used to quantify early chemotherapeutic effects on tumor metabolism. Furthermore, the duration Of the cYtostatic effect can be assessed by PET.Therefore, different chemotherapeutic protocols may be compared on the base of PET studies.

IMMUNOSCINTIGRAPHYOFPROSTATECARCINOMA UTILIZING1nln-CYT-356

PURPOSE: This initial clinical study was undertaken to detect metastatic prostate carcinoma with the investigational scintigraphic agent, nlIn-CYT-356, a site-specifically radiolabeled immunoconjugate of the monoclonal antibody 7Ell-C5.3. METHODS: 20 patients with prostate carcinoma were injected with varying doses (0.1 - 10.0 mg) of CYT-356 radiolabeled with 4.0 - 5.0 mCi of l l l I n under a protocol approved by the local institutional review board. Whole body planar images were obtained on two occasions 1 - 5 days following injection. SPECT images of the abdomen and pelvis were also obtained during one of the imaging sessions. Baseline and follow-up hematolo~ies, blood chemistries, HAMA titers, and urinalyses were obtained in all patients. Each patient was also evaluated by traditional imaging modalities (i.e., bone scan, CXR, CT, or MRI). RESULTS: A sensitivity of 76% was demonstrated in the detection of prostate carcinoma utilizing 111In-CYT-356. Tumor sites were visualized in the prostate, bone, lymph nodes, and lung. In addition to detection of known lesions, occult sites of tumor were identified and subsequently confirmed by additional imaging studies. No toxic effects were detected with antibody injection. None of the 18 patients followed out to 4 weeks developed a positive HAMA titer. CONCLUSION: This preliminary study suggests that detection of both known and occult sites of prostate carcinoma are possible with nlIn-CYT-356 and that it can be safely administered.

PO-4R1-107

PO-4R1-108

l.Urgancloglu,I.Cepni,F.Uzum,C.Onsel,N.Kahraman, [.Uslu,M.Arvas,F.Demir ~r~¥a~,n,S.Guvener,T.Eapicioglu, N.Tolun, E.Erkun Departments of Nuclear Medicine,Obstetrics and Gynecology,Cerrahpasa Medical Faculty, Istanbul, TURKEY

A van Dongen, KJ Tusenius, MHJ van Oers, PJM Bakker, EA van £
PREOPERATIVE ASSESSMENT OF LYMPH NODES METASTASES IN GYNECOLOGIC MALIGNANCIES BY PELVIC LYMPHOSCINTIGRAPHY

67 GALLIUM UPTAKE AND ACTIVITZ OF PROLIFERATION MARKERS IN-LYMPHOM~ 67-Gallium is u@ed in the staging of mali gDant lymp no_~. b/v~a uptake is hignest in high grade mal19%qan_t mon- o~ggAn ly~Phoma (NHD)..LQw and lnt~rmediate ~ a d e col~rz~t~ndto tak~ up l e s s galllum~ suggestingthere is a cor at~on re~ween ga£11ttm ~ ar~ prollzeration activity. TO investigate t h i s correlation, in [email protected] with lympnoma 67-GA uDEaxe was compared wlth the his~:ologlcal gra~e and with OI~T9 (transferrin re.ceptor), KI67 (nuclear antigen ) and BrdUrd ~v_nyr~.o/ne anaLog_on) incorporation in DNA as p rpilzera~1on markers. Untlll ~ 16 patients entered the study. 67vGa" sclntl .gr/@phy was performed 48 hrs after the in3ec~1on of 185 ~ q . 67--Galliumci~t. 67-G¢? uptake was es£1mated semica/antltatively: 0=no uptake, l=sternal, 2>sternal and izver. After sclntl~raphy, the lymphoma was removed and the expression ol.r_~e prpllfei~a~1on markers was assessed as ~ l i u ~ the h i s t o ~ o ~ ~ d e ~ assess ~ e in vivo ,ruuru zncorpora~zon r_ne 15atlents recleved 500rag BrdUrd z. v 2exore 21opsy. The group of patlents consisted of 5 reactive lymphoma, .low grade i~D, 6 intermediate/high grade NHD and 3

This study was performed to determine the usefulness of the pelvic lymphoscintigraphy by c o r r e l a t i n g the preoperative s c i n t i g r a p h i c findings with pathologic findzngs for the assessment of metastatic lymph nodes involved by gynecologic malignancies. The study was carried out in 5 subjects wlthout(CNL) and 23 p a t i e n t s with gynezologie malignancies. Of these p a t i e n t s 16 had carcinoma of cervix uteri(CCU) (12 stage I, 3 stage I I , and 1 stage I I I ) , 4 had carcinoma of corpus uteri(CCRU) and 3 had vulva cancer(VC). For the s c i n t i g r a p h i c i n v e s t i g a t i o n , 37MBq of Tc-99m Rhenium sulphide colloid in l e s s than 0.5ml were applied at each side. In 6 s u b j e c t s perianal injection(PAI~(2 in CNL, 1 in CCU, 3 in VC) and in 22 p a t i e n t s paracervical injection(PCI) were done. All subjects also received b i l a t e r a l pedal dorsal injection 3 hours a f t e r the f i r s t i n j e c t i o n . Images were obtained in multiple p r o j e c t i o n s at 3 and 6 hours a f t e r the f i r s t injections. All p a t i e n t s were operated on within the f i r s t five days aft~n- the s c i n t i g r a p h i c evaluation. The dissection of ~elvic n o d e s ( i n g u i n a l , i n t e r n a l , external and common lilac nodes) wa§ performed and histologically investigated. Results:

Total . . . . . . . . . . . . . . .TP . . . . . . . .TN . . . . . . . . . FP . . . . . . .FN . CCU 4 9 3 16

CCRU VC

f

3

i

l

1

-

CNL 4 I ....................................... Total 6 17 5 -

4 3 5 28

TP:True po~itive.TN:Truene~gtive,Fe:FalsePositive,~q:Fal~e negative ~ensltlvlty:100%, Speclf~clty:77%, Accuracy:S2% In our preliminary study,the high sensitivity rate may be due to PCI method which allows more apparent internal iliac lymph nodes visualization than PAI. In conclusion, PCI in conjunction with bilateral pedal dorsal i n j e c t i o n can assessment of malignancies.

be recommended in the p r e o p e r a t i v e l y m p h nodes involved by gynecologic

Histology reactive lowgrade ~t/high .

,

Galliumuptake 0 0,0.0. O 0 0~3 ' ' ' i, 2 3 3, 3 3 i,l~l' '

OKT9 2-37 21 8-92 3s

KI67
BrdUrd 1,7-3 6 l-l, 6' 5-10 7 1,8-~,9

Conclusions:-67Gallium uptake seems to have a correlation with the his%ol.ogical grade. $In this small .9-.~oupof patients Ol~f9 and K167 tend to nave no corre-a~1on wlth gallium uptake and histological grade. -BrdU.rd incorporation seems to have a correlation with the hi'stologlcal grade. - ~ T n e r stfldy ha~ to be done to investigate whether ~].Urd... znco~oo{ation and,. proba~, y .more i m p o ~ , t, the rom r_ne ~raurct inco rlx2ra~1on calculated potential do ublin@ tlme~ c a n diTferentlate between low and intermeoaate/b_igh grade malignant lymphonmu

685

Wednesday, 4 September 1991

PO-4R1-109

PO-4R1-110

H. VanbiUoen, M. Hoogmartens, M. De Roo, A. Verbruggen Lab. Radiopharm, Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

T. VANDER BORGgT, S. PAUWELS, L. LAMBOTTE. University of Louvain Medical School, UCL 54.30, av. Hippocrate 54, B-1200 Brussels, Belgium.

C O M P L E X E S OF 99~Te-WITIt TETRAGLYCINE, PEN-

TAGLYCINE AND HEXAGLYCINE: PREPARATION AND B I O D I S T R I B U T I O N IN M I C E

IN

VITRO INCORPORATION OF TW/NIDINE ("]DR) BY TISSUE VIVO MEASffREMENT OF

BIOPSIES : A REFERENCE FOR IN CELLULAR PROLIFERATION WITH PET.

with 99mWC, which represent an interesting group of new 9 mTc_ chelates. More derivatives have to be examined to elucidate the potential of this class as new diagnostic agents for nuclear medicine.

Validation of [2-ziC]Tdr PET imaging for measurement of cellular proliferation has been achieved in animals by comparison of the [2-zZC]Tdr PET signal with the true DNA incorporation of [6-3B]Tdr administered in vivo. In order to develop a validation method that could be applied to man we have now evaluated whether the Tdr incorporation measured in biopsy specimens incubated with [2-14C]Tdr correlates with the metabolic capacity measured in vivo. 20 rats were injected with 5Opel [6-3H]Tdr (3 controls, 17 regenerating livers : RL) and sacrificed i0, 30 and 120 mln after injection. Excised liver (Ig) was further incubated with lOpCi [2-14C]Tdr in a Krebs solution for a period identical to the in vivo study (i0, 30 and 120 mln). 3H and Z4C activity was measured in the DNA fraction. In vivo, the amount of 3H radioactivity incorporated into DNA progressively increased with time in RL compared to controls. In EL liver samples incubated for 10 or 30 min~ the 14C radioactivity carried by the DNA fraction was similar to that found in controls. However, after 120 min incubation, a 9-fold increase in 14C DNA activity was observed in EL compared to controls. A positive correlation was found between 14C DNA activity after 120 min incubation and in vivo 3B DNA activity at 120 min (r= 0.81; p<0.005). Our data indicate that the amount of labelled Tdr incorporated in vitro by biopsy specimen correlates with the Tdr incorporation observed in vivo, although the incorporation rate is faster in vivo than in vitro. The method could be useful for validation of the specificity of the [2-11C]Tdr PET signal in man.

PO-4Rl-111

PO-4R1-112

A.Vattimo,P.Bertelli,L.Burroni,*G.Greco,*A.Bartolomei Nuclear Medicine Unit and *Institute of Ophtalmologic Sciences, University of Siena - Italy.

V u i l l e z J.Ph.(1), M o r o D. (2), F e r r e t i G. (3), B r a m b i l l a E. (4),Brichon P.Y. ( 5 ) , B r a m b i l l a C. (2) (1)LER URA CNRS 1287,(2)Pneumology,(3)Radiology, (4)Pathology,(5)Thoracic Surg. C H R U G r e n o b l e , F r a n c e

OCULAR MALIGNANT MELANOMA (OMM): TUMOR PROMINENCE (TUPR) AND IMMUNOSCINTIGRAPHIC SENSITIVITY Immunoscintigraphy with monoclonal antibodies to melanoma associated antigens can be used as an additional test to detect OMM in clinically difficult cases. 30 patients (pts) with clinical and instrumental suspicion of OMM were studied. In each pt ophthalmoscopy, fluorescein sngiogrephy, computerized perimetry and ultrasonography were performed. TUPR and mass wideness were calculated by echobiometry and ophthalmoscopy. Scintigraphic data were obtained 6-8 hours after i.v. injection of 740 MBq 99mTc-F(ab") of Mab225.28S, by means of a SFOV Anger-camera equipped with a LEHR collimator (pixel size=1.72 mm;frame-time=1200").Raw and filtered scintigraphic data were evaluated by consensus view of two blinded observers. In 21/30 pts histopathologic diagnosis was obtained. 3/21 pts had doubtful angiography due to limited transparency of dioptric medium. 8/21 pts (38%) were false negative (FN) and 13/21 (62%) true positive (TP) on immunoscintigraphy; mean TUPR was 3.?+/-3.67 mm in FN group and ?.11+/-2.98 mm in TP group (p .05). Moreover, on the basis of TUPR all 21 pts were divided in two groups: GI (TUPR 6 mm) FN=5/7; TP=2/7 - G2 (TUPR 6 mm) FN=3/14; TP=11/14 . These data show a close correlation between tumor size and scintigrafic sensitivity. In spite of this limit scintigraphy play an important diagnostic role when ophtalmoscopy and fluorine angiography are doubtful.

IMMUNOSCINTIGRAPHY (IS) U S I N G 1 1 f I N - L A B E L E D A N T I - C E A F ( a b ' ) 2 IN L U N G C A N C E R S T A G I N G

We have shown that tetrapeptides, e.g. tetraglycine (G4), carl act as tetradentate ligands to form stable complexes with 99mTC. To investigate the influence of peptide chain length on the labelling characteristics and on the biological behaviour we have now examined the complexes of 99mTc with pentaglycine (Gs) and hexaglycine (G6) Labelling of the ligands was studied by two methods. In the direct method 100/~g SnC12 and 0.5 ml 99mTc generator eluate were added to 0.5 mg of the ligand in phosphate buffer of different pH. Reaction mixtures were analyzed by ITLC, RP-HPLC and dectrophoresis. Labelling at pH > 10 was required to obtain a single radiochemical species This remained stable in function of time, also after HPLC isolation and storage at lower pH. Exchange labelling (100°C) in the presence of stannous tartrate pH 5 afforded 80 to 90% of a compound with the same retention time on HPLC as the peak formed during direct labelling. Complexes of 99~Tc with G4, G5 and G6 behave similarly in electrophoresis: they do not migrate in acidic medium, but as pH raises migration to the cathode increases. This suggests that the terminal COOH is not involved in complex formation. Biodistribution of HPLC-isolated peaks was studied in mice (n=5) at 10 rain and 30 rain p.i.. OIH was coinjected as internal biological standard. The three tracer agents are rapidly cleared from the blood, mainly by the kidneys. However, renal retention and uptake in the hepatobiliary system increase from 99mTc-G4 to 99mTc-G6.

The results show that oligopeptides form easily stable COmgpgleXes

686

One o f t h e m o s t i m p o r t a n t p r o b l e m in l u n g cancer staging is determining patient o p e r a b i l i t y , w h i c h d e p e n d s on m e d i a s t i n a l or m e t a s t a t i c involvement. IS has b e e n p r o p o s e d as a complement to m o r p h o l o g i c a l imaging (CT, MRI). 21 p a t i e n t s w e r e s t u d i e d (stage I=l, II=3, III=8, I V = 9 ) . T h e r e w e r e 15 s q u a m o u s cell carcinomas, 4 adenocarcinomas, and 1 s m a l l cell cancer. Mean CEA plasma level was 12.5!28.5 ng/ml (0.7 to 126, N < 5 ) . B o d y s c a n n i n g and SPECT w e r e p e r f o r m e d 3 days a f t e r an i n j e c t i o n of Img of l l l I n - a n t i C E A F(ab')2 (IIIMBq).AII IS w e r e i n t e r p r e t e d b l i n d l y b y the same o b s e r v e r . Among 21 p r i m i t i v e tumors, 15 (71%) were detected by IS.There were 9 known mediastinal localizations, 5 of w h i c h were c o n f i r m e d by IS. IS s h o w e d 3 a d d i t i o n n a l m e d i a s t i n a l loci, 2 of w h i c h c o r r e s p o n d e d to l y m p h n o d e s
Wednesday, 4 September 1991

PO-4R1-113

PO-4R1-114

I. Zanzi, W. Robeson, V. Vineiguerra, N. Kamdar, S. Kroop, T. Chaly, J.R. Dahl, P. Schulman, and D. Margouleff. North Shore University HospitalCornell University Medical College, Manhasset, New York, U.S.A.

S.T. ZWAS Y. RAMON, R. YAHALOM & P. RATH Chaim Sheba Medical Center and Sadder School of Medicine, Tel Aviv University, Tel Aviv, Israel LYMJ'I-IOSCINTIGRAPItlCASSESSMEgF OF CERVICAL LYMPHADENOPATHY IN PATIENTS WITH ORAL CARCINOMA

IMAGING OF G A S T R O I N T E S T I N A L

NEOPLASMS

WITH PET.

The purpose of the study was to identify gastrointestinal tumors and/or metastases by PET using F18-2-fluorodeoxyglucose (FDG). PET studies were performed in 20 patients (pts) with pancreatic tumors (17 adenocarcinomas, 2 islet cell tumors and 1 insulinoma) and in 4 with hepatic metastases secondary to colorectal carcinoma. Data were acquired for 1 hr post injection in 14 contiguous 7 nlm slices, reconstructed, and corrected for attenuation. Suspicious areas were evaluated using the Differential Absorption Ratio (DAR) technique, PET and CT images correlated in 12 pts with pancreatic adenocarcinomas, 2 pts with n o n - a d e n o c a r c i n o m a pancreatic tumor and 4 pts with colorectal tumors. Liver metastases were identified by PET in ll pts. In 6 pts with pancreatic DAR's adenocarcinoma and good CT correlation, m e a n of suspicious loci in pancreas (5.95) and liver (7.31) were significantly higher than in control areas (2.69, p<0,001). In the 4 pts with colorectal liver metastases, DAR's (6.44) were also significantly higher than the control areas (p<0.001). We conclude that an increase of FDG uptake as detected by PET may provide a useful in vivo marker in pancreatic and other gastrointestinal neoplasms. Initial experience in m o n i t o r i n g changes in tumor activity in response to therapy is encouraging.

The state of cervical lymphatics in oral squamous cell carcinoma (OSCC) has a major impact on the course of disease. Clinical and radiologieal investigations of cervical lymphatic metastases have had limited success. A recently introduced method of cervical lymphoseintigraphy (CL) (Zwas & Ramon) in normals using Tc-99m rheniumsulfid colloid (RSC) proved to be highly accurate in demonstrating major cervical lymphatic chains draining the oral cavity. These chains are the common sites of lymphatic spread in OSCC. Twenty-two patients with OSCC presenting with 36 palpable lymph nodes measuring 0.5--4 (mean 1.7) cm underwent CL prior to surgical nodes removal or biopsy to assess the state of their lymphadenopathies. Anterior and bilateral CL views were obtained 24 hrs after bilateral cheek mucosal injections o-f 2-3 mCi Te-99m RSC using a gamma camera with a high resolution collimator. Each palpated gland was located by a Co-57 point source marker on the scan. The gland radionuclide upfake was graded as normal, hot (reactive) or c01d (metastatic). Final correlations with histopathological findings disclosed the following for palpated cervical glands: Lymphoscimigraphy (nodes uptake) Histology Metastases Normal/reactive

Cold 25 2*

Normal/hot -

-

9

*Post-oral, neck surgery. Sensitivity: 25/25 = 100%; Specificity: 9/11 = 82%; Accuracy: 34/36 = 94%. We conclude that this CL method is very efficient in demonstrating cervical lymphatics and highly accurate for assessing their involvement in metastatic OSCC.

687

PO-2L1-50A

PO-2L1-50B

A JAVAID, D L EWINS, S SHAH, A M McGREGOR & JJ BARRETT Departments of Nuclear Medicine and Medicine, King's College Hospital, London SE5 9RS

R.A. Vald~s Olmos, F.C.A. den Hartog Jager, B.G. Taal, C.A. Hoefnagel. The Netherlands Cancer Institute, Amsterdam, NL.

OCTREOTIDE THERAPY FOR ACROMEGALY: ASSOCIATION OF GALL BLADDER MOTOR FUNCTION WITH GALLSTONE FORMATION.

IMPROVED CLINICAL VALUE OF Se-75-HCAT DURING LOPERAMIDE ADMINISTRATION IN PATIENTS WITH ILEAL DYSFUNCTION.

Gallstone formation is a recognized complication of Octreotide therapy for acromegaly. We have studied gall bladder motor function in 9 acromegalic patients before, 24 hours later,six months and at I year of octreotide(Sandostatin) therapy. 150 HBg of Tc99m Mebrofenin was injected i.v after 6 hours of fasting. Dynamic data was acquired 75 minutes post injection for 30 minutes. Intravenous cholecystokinin was used to induce gall bladder emptying. Regions of interest were drawn over entire gall bladder and adjacent liver for background correction and time activity curves generated. Gall bladder ejection fraction (OBEF) and gall bladder ejection rate (GBER) were determined. 24 hours post therapy, GBEF and GBER decreased by 57+/-23~ and 63+/-19~/min respectively as compared to the pretreatment values. After 6 months therapy, a marked reduction i n GBEF(>35%) and OBER(>q0%) persisted in 4/9 patients. 2 of these, developed gallstones. After I year therapy, gall bladder was not visualized on 2 ocassions in one patient, others showed gradual improvement in GBEF and GBER. Sandostatin showed an acute stunning effect of tbe gall bladder motor function in all patients, persisting in some upto I year. This data demonstrates a clear association of gall bladder motor function with the development of gall stones. Gall bladder ejection fraction and ejection rate may be useful predictors of gallstone formation.

In conditions of ileal damage (radiation, resection), a rapid small bowel transit due to an abnormal motility may be an important factor in the mechanism of bile acid malabsorption (BAH). Since loperamide, a widely used antidiarrhoeal agent, can reduce bowel motility, imaging and retention studies of Se-75-HCAT under loperamide administration (daily standard dose:4mg) were performed in i0 patients suspected of BAM in order to document the aetiology of ileal dysfunction and adjust the treatment. In 3 patients with ileal resection (IR) between 20 and 50 cm and in 1 patient without IR, retention was normalized under loperamide (range 7-day values: 10-17~) in comparison to abnormal baseline studies (<5% within 4 days). Sequential scintigraphic images showed improvement of 8eHCAT absorption and enterohepatic circulation accompanied in one case by prolonged colonic retention. In line with the scintigraphic amelioration the clinical response was goed. The degree of SeRCAT abnormality was decreased by loperamide in 2 other patients (IR:25/40cm) accompanied with relief of symptoms. In 3 patients with IR >10O cm and in 1 with 80 cm, SeHCAT remained severely abnormal.

Conclusions: 1) In c o n d i t i o n s of demonstrated i l e a l d y s f u n c t i o n , r e d u c t i o n of small bowel m o t i l i t y by loperamide may improve SeHCATabsorption and r e t e n t i o n . 2) I n t e r v e n t i o n with loperamide i s e a s y to perform and enhances the c l i n i c a l v a l u e of the SeHCAT t e s t with d i r e c t t h e r a p e u t i c i m p l i c a t i o n s . 3) S e q u e n t i a l imaging i s e s s e n t i a l to i n t e r p r e t the changes in the SeHCAT pattern.

PO-2R1-43A

PO-4L1-61A

K. Ozker, B.D. Collier, R.A. P a t t i l l o , H.M. Abdel -Dayem, A.T. Isitman, R.S. Hellman, A.Z. Krasnow, A.C.F. Ruckert, L. Trembath. Medical College of Wisconsin, Milwaukee, Wl USA

L.Fridrich, D,HeUte, M.Seyr+,)N.Mutz t),- B.Rohrbacher, G,Riceabona. C l i n i c for N u c l e a r M e d i c i n e and +) Clinic for Anaeetee&ology, University of Innsbruek, Austria

Tc-99m LABELED ADRIAMYGIN: A NEW AGENT FOR STUDYING ADRIAMYCIN PHARMACOKINETICS.

CONTINUOUS SCINTIMECTRIC BED-SIDE-MONITORING OF LEFTAND RIGHT VENTRICULAR FUNCTION DURING INTENSIVE CARE LV- or RVEF have been identified as predictors for survival in pts. after myocardial infarction or in septic patients respectively. Since Gamma-Camera assessment of LVEF and RVEF is cumbersome in the critical ill and does not allow continuous monitoring, we investigated the poseibiIity to use a new miniaturieed scintillation detector for monitoring of LV- and RVEF in critical ill patients. Methods: After red btood-ceII labeling with 99mTc the "Cardioecint-System" including a small directly to the patients chest attachable probe by a line directly connected to a PC interface allows immediate.visua]isation of an actual beat by beat or gated ventricular function curve on the PC screen. Ventricular function data can be reviewed as a~:trend curve when monitoring is still going on or there after. Results: As a first attempt good correlation between "eardioscint" and imaging derived LV- and RVEF in clinical stable patients referred for blood pool scintigraphy could be revealed: r= 0,79 and r= 0,93 respec~ tively; for RVEF changes assessed simultaneously by both in etrumentations cerre]ation was: r= 0,88 (n= 17). LV or RVEF monitoring in pts. on artificial respiration (n= 12 pts until] now, 3 deceased) showed good agreement with clinical course and invasive measured v a r i ~ ab]es. Conclusions: LV and RVEF-cardioseint monitoring corretared well with imaging and outcome. Its practicability could be demonstrated during intensive care even under conditions of artificial respiration.

Adriamycin (ADM) is a wide spectrum antineoplastic antibiotic whose action is based on binding and interaction with DNA. We synthesized TC-99m-ADM using a tin-electrode electrolytic procedure (electrical charge of 0 . 1 8 coulombs) with a labeling yield of 97.7 (+/- 0.5)%. Both TLC and rat biodistribution studies demonstrated that TC99m-ADM was stable. In rats the activity was rapidly and selectively taken up in the l i v e r and excreted into the bile with no stomach or thyroid uptake. Functionality of TC-99m-ADM was studied by incubating Tc-99m-ADM with cultured human ovarian carcinoma (OC) and choriocarcinoma (CC) cell lines which had never been exposed to ADM. Two hour uptake was 2.82 ( + / - 0,26) % f o r OC and 2.41 (+/0.44)% f o r CO. 24 hour OC uptake of Tc-99mpertechnetate and 48 hour OC uptake of Ga-67 c i t r a t e were only 1/6 and 1/4 as great as the 2 hour DO uptake of Tc-99m-ADM, T h e s e results suggest t h a t Tc-99m-ADM molecule sustains only minimal damage during the e l e c t r o l y t i c complexation and has potential for studying ADM pharmacokinetics.

688

Monday, 2 September 1991 Monday, 2 September 1991 TP-2K1-3 Wo!fTSOssmanD E-M± Dept. of N u c l e a r M e d i c i n e , J o h a n n e s G u t e n b e r g - U n i v e r s i t y , Mainz, G e r m a n y

TP-2K1-4 M. Telqmann, W. Brandau, J. Sciuk, O. S c h o b e r K l i n i k u n d P o l i k l i n i k f~r N u k l e a r m e d i z i n Westf~lische Wilhelms-Universit~t D-4400 M~nster, FR Germany

A U F G A B E N DER M T R A A M G A N Z K O R P E R Z A H L E R Mit dem G a n z k 6 r p e r z ~ h l e r sind die q u a l i t a tive und q u a n t i t a t i v e E r f a s s u n g yon k l e i n sten M e n g e n i n k o r p o r i e r t e r o d e r a p p l i z i e r ter R a d i o a k t i v i t ~ t s im m e n s c h l i c h e n K 6 r p e r m6glich. Ziel des V o r t r a g e s ist die E r l ~ u t e r u n g der u m f a n g r e i c h e n Q u a l i t ~ t s - und E i c h m e s s u n g e n (t~gliche P e a k k o n t r o l l e , U n t e r g r u n d m e s sung, q u a n t i t a t i v e E i c h m e s s u n g e n ) , d e r e n D u r c h f ~ h r u n g w e s e n t l i c h e A u f g a b e n einer M T R A am G a n z k 6 r p e r z ~ h l e r sind. D a n e b e n w e r d e n kurz die in M a i n z d u r c h g e f6hrten Untersuchungsmethoden vorgestellt: R e s o r p t i o n s - R e t e n t i o n s m e s s u n g e n bei Patienten, I n k o r p o r a t i o n s m e s s u n g e n zur Personaldberwachung, Kontrollmessungen nach Tschernobyl. in der E i n l e i t u n g w i r d in w e n i g e n S ~ t z e n der Geriteallfbau am B e i s p i e l des M a i n z e r Ganzk6rperz~hiers aufgezeigt.

Q U A L I T A T S K O N T R O L L E IN DER R A D I O C H E M I E L U X U S O D E R N O T W E N D I G K E I T F O R DIE E L I N I S C H E ROUTINE ? Die E n t w i c k l u n g i m m e r s p e z i f i s c h e r e r R a d i o pharmaka f~hrt zu h o h e n Anforderungen an deren radiochemische Reinheit und wirft die Frage einer Qualit~tskontrolle (QC) auf. W~hrend mit etablierten Radiopharmaka (Knochen-Kits, DTPA, Therapiekapseln etc.) s e l t e n P r o b l e m e zu e r w a r t e n sind, w i r d d i e Notwendigkeit einer Qualit~tskontrolle vor a l l e m bei neueren, s p e z i f i s c h e r e n P r ~ p a r a t e n (Tc-HMPAO, Tc-MAG3, I - E s t r a d i o l , m o n o k l o n a l e Anitk6rper etc.) kontrovers diskutiert. Weiterhin last die Vereinheitlichung der e u r o p ~ i s c h e n G e s e t z e erwarten, d a b e i n e QC v e r s t ~ r k t g e f o r d e r t w i r d (i). In der v o r l i e g e n d e n A r b e i t w e r d e n v e r s c h i e d e n e m o d e r n e M e t h o d e n (HPLC, DC etc.) v o r g e stellt, die d i e r a d i o c h e m i s c h e R e i n h e i t d e r wichtigsten Radiopharmaka sicherstellen k6nnen. D a b e i w i r d ein S c h w e r p u n k t auf die Praktikabilit~t dieser Methoden (apparativ einfach, schnell, sicher) in d e r t ~ g l i c h e n R o u t i n e gelegt. A n h a n d v o n B e i s p i e l e n w i r d die P r o b l e m a t i k von Routinekontrollen oder stichprobenartigen 0 b e r p r ~ f u n g e n e i n g e h e n d d i s k u t i e r t u n d entsprechende Empfehlungen werden vorgestellt. (i)

E G - E n t w u r f I I I / 9 0 6 2 / 9 0 - E N R e v . l Zur Anderung der Richtlinie 75/318/EWG

TP-2K3-2

TP-2K3-3

A-C Bergh*, M. Fj~illing*, B-A JSnsson**, C. Wikkels6*** *Division of Nuclear Medicine, Department of Clinical Physiology, **Department of Radiation Physics, ***Department of Neurology, Sahlgrenska Hospital, G6teborg, Sweden

Robin A. Greene, CNMT Yale University School of Medicine, New Haven, CT USA

In-II1-OXINE AND T c - 9 9 m - H M - P A O L E U C O C Y T E "SCINTIGRAPHY IN THE DIAGNOSIS OF BRAIN ABSCESS Leucocyte scintigraphy (LS) is used as a diagnostic tool in differentiating cerebral abscess from inU'acranial tumour. Since 1983, we have done 31 LS in 31 patients. In-111-Oxine was used between 1983 and 1988 and Tc-99m-HM-PAO (Ceretec,Amersham) since 1988 . We have reviewed these 31 LS to assess the diagnostic value of LS, and to compare I n - l l l Oxine and Tc-99m HM-PAO as labeling agents. To see if time between inj. and imaging could be shortened, the patients were scanned 4 and 24 hrs after Tc-99m HMPAO inj. Methods; Autologous In-111-Oxine labeled leucocytes were given (i.v.) to 16 patients. The activity was 7-10 MBq, and images were acquired 24 hours after the injection. 15 patients were injected with 70-100 MBq Tc-99m-HM-PAO labeled autologous leucocytes. Images were acquired 4 and 24 hours after the injection. All LS were blindly reviewed, and the results were scored as positive or negative. The final diagnos was based on results of surgery, histopathology and in a few cases on the clinical course. Results: Final_ In- 1110xine Tc-99m HM-PAO . Pos Neg Po_s _ Neg Abscess 1 1 2 Tumour 13 3 7 Other 2 2 Both ln-111 Oxine and Tc-99m HM-PAO, LS gave false negative and false positive results. Two patients with false negative LS were treated with dexametason. The false pos. scans in tumour cases were of lowmoderate intensity . The patient with a true pos. scan had an early and very intense uptake, and was not on steroids. Early and late Tc-99m HM-PAO LS gave similar results. Conclusion: The two labeling techniques gave similar results. The results of Tc-99m HM-PAO LS were the same for the images 4 and 24 hrs alter injection.

TECHNICAL CONSIDERATIONS FOR NMR BRAIN SCAN COREGISTRATION WITH SPECT Magnetic Resonance (MR) and Single Photon Emission Computed Tomography (SPECT) provide complementary information. There exist many acquisition techniques and imaging processing algorithms that make it possible to superimpose the functional features of the SPECT study with the anatomical features of the MR study which serve to produce a single "hybrid" SPECT-MR image. There are many technical considerations that must be taken into account when the MR image is to be used for SPECT image correlation. Imaging variables such as slice thickness, interslice spacing, field of view size, and matrix sizes must be carefully planned. In addition, an appropriate image marking technique employing extrinsic or intrinsic markers must also be standardized, for these markers will determine how accurately the image processing algorithm will overlay the data from the two imaging modalities. Provided the above considerations have been carefully taken into account, the diagnostic availability of the hybrid SPECT-MR imaging techniques can greatly improve the reliability of psychiatric diagnosis and the prediction of drug treatment responses in many of the disorders being studied.

689

Tuesday, 3 S e p t e m b e r 1991 - W e d n e s d a y , 4 S e p t e m b e r 1991 T u e s d a y , 3 S e p t e m b e r 1991

TP-3K3-2

TP-3K3-4

Sally J. Bentley, Department of Nuclear Medicine, Fremantle Hospital, P.O. Box 480, Fremantle 6160, Western Australia.

..H..Pintelon, A. Piepsz AZ VUB, Dept Radioisotopes, Brussels, Belgium

SPECr QUANTITATIONOF VOLUMESAND ACTIVITYIN ANTHROPOMORPHICPHANTOMS. Phantoms comprising a sheep femur embedded in shaped wax blocks were prepared to simulate human body sections. Samarium-153 solutions of known volume and activity were introduced into plastic inserts in the phantoms to simulate focal bone uptake in patients. Tomographic acquisitions were performed on the Scintronix 480-20 SPECT system and volume and activity values were calculated, then compared with the actual volume and activity dispensed. SPECT phantom acquisitions were performed for 180 and 360 degree rotations in each of four orbits, one circular, the others elliptical. Reconstruction was performed by back projection for each of three filters - Butterworth, Hamming and Ramp function. The voxel elements per slice were then summed and the volume of the sample calculated for a range of fixed thresholds. Correlation was determined by linear regression analysis. Estimation of activity was performed on decay-corrected data also corrected for attenuation using the Chang first order correction. The counts per voxel per slice were then summed and compared with SPECT counts from a standard of known volume and activity. The phantom activity was then calculated by simple proportion. For volumes exceeding 30cc there was good correlation (r = 0.8) between the true volume and that estimated by SPECT at a fixed threshold of 10%. However, for volumes less than 30cc accurate SPECT quantitation was highly dependent on threshold. Estimation of small volumes was improved by development of a simple slice index/threshold algorithm which achieved excellent correlation (r = 0.92) of SPECT - calculated volumes with those of the phantom. Testing of the index algorithm was then performed on t,n vt.vo phantoms to assess the potential for SPECT quantitation of dosimetry for samarium- 153 radiotherapy.

QUANTIFICATION OF OESOPHAGEALTRANSIT IN CHILDREN, USING KRYPTON-81m. Various conditions like congenital oesophageal abnormalities, peptic and caustic oesophagitis, neuromuscular disorders, or recurrent lung disease may interfere with the oesophageal peristalsis. Three lumen manometry is the technique of choice for the detection of these abnormalities, but is invasive and can hardly be repeated. During these last years, Krypton 81m swallowing tests are routinely performed in our department in infants and older children. Compared 1o Tc 99m colloid , Krypton has obvious advantages, particularly in children : due to the utrashod hall- life of the tracer, very high doses may be administered to the patient, thus providing high quality images, while the radiation dose to the patient remains negligeable. There is no problem of internal or external contamination and the test may be repeated as often as necessary. Several precautions are however mandatory for optimal quality of results : precautions related to the Rubidium generator (absence of Rubidium contamination, type of liquids perfused through the generator), precautions related to the ultrashort life of Krypton (length and diameter of the output catheter, time delay betweenthe production of Krypton and the administration to the patient); precautions related to the quality of the bolus administered to the patient (quantity of liquid administered,using either a plastic cup or a syringe, in function of the age); finally, precautions with the type of image processing: simple sequential images or time activity curves are generally insufficient for a correct diagnosis and should be implemented by means of functional

time imagesor condensedimages.

W e d n e s d a y , 4 S e p t e m b e r 1991

TP-4K2-5

TP-4K2-2 P~.Trindev,

" x M.Garcheva,E.Sheiretova D.Nzkolov,

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PRACTICAL ASPECTS OF BIODISTRIBUTION STUD1E~ WITH RADIOPHARMACEUTICALS IN MICE

AND

DETERMINATION

By the proposed

M. Hoogmartens, D. Crombez, M. De Roo, A. Verbruggen Lab. Radiopharm. Chem. I.F.W. and Nuclear Medicine, U.Z. Gasthuisberg, K.U.Leuven, Belgium

Bulgaria

SCINTIGRAPHY

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Mice are particularly attractive as animal species for the initial screening of the biological properties of radiopharmaceuticals. They have a low cost, are safe and easy to handle and radioactivity of complete organs can be counted. Before tracer injection, ~edation can be accomplished by the I.M. injection of HypnormR and body mass is then determined. Fixation of the animal in a special holder permits convenient I.V. injection of the tracer solution via a tail vein. The injection volume should not surpass 0.1 ml and a 26 G needle is most appropriate. The solution should contain no methanol or acetone and at most 10% of ethanol. A radioactive concentration of 111 kBq/ml is recommended for a 99mTc compound to not oversaturate the Nalfrl) scintillation counter. Ideally a second tracer agent with well-established biodistribution and labelled with an other radionuclide should be added to the solution in a suitable concentration. This permits to reject animals with disturbed uptake pattern. After injection the mice can be housed in an ordinary laboratory glass beaker on absorbing paper (towel) to avoid loss of radioactivity in urine and faeces. The most rapid and convenient way to sacrifice the animal is decapitation, and it allows also to collect easily up to 1 g of blood in a tared tube. During decapitation the mice should be wrapped in the absorbing paper to avoid loss of excreted urine or faeces. Spilled blood must be collected on a second towel. Ureter and urethras should be ligated before dissection of bladder and kidneys. Blood has to be removed from the heart. All organs and other body parts should be dissected and counted. The sum of counts in all organs (except the tail) + counts on absorbing papers equals the I.D.. Results are more reliable with this method than by using a standard. Activity "m the tail should also be measured to reject animals with extravascular injection.

Thursday, 5 September 1991

Thursday, 5 September 1991 TP-5K0-1

TP-5K0-2

MJ Sehelen, CS Greuter, HJ Pijpers, A v a n Lingen, OS Hoekstra, G J J Teule. Dept of N u c l e a r Medicine. Free U n i v e r s i t y Hospital, De B o e l e l a a n 1117, 1081 HV Amsterdam, the Netherlands.

S v a n Balen, A Pierik, OS H o e k s t r a , JC Roos, GJJ Teule, A van Lingen. Dept of Nuclear Medicine, Free University Hospital, Boelelaan 1117, 1081 H V A m s t e r d a m , T h e N e t h e r l a n d s .

R O U T I N E S P E C T F O R KNEE I M A G I N G ? In p a t i e n t s (pts) w i t h c o m p l a i n t s of the knee, m u l t i p l e p l a n a r views are n e e d e d for an a c c u r a t e localisation and d e l i n e a t i o n of a b n o r m a l i t i e s ( G r e u t e r 1990). In the p r e s e n t s t u d y we c o m p a r e d this a p p r o a c h w i t h SPECT. P a r a m e t e r s w e r e d i a g n o s t i c a c c u r a c y and c o n v e n i e n c e for t e c h n i c i a n s and pts. T w e n t y pts w i t h c o m p l a i n t s of the knee w e r e studied. A f t e r QC (rotation c e n t r e / h o m o g e neity), S P E C T (180, AP, 30 angles, 60 s e e / a n g l e ) was p e r f o r m e d f o l l o w e d by m u l t i p l a n a r i m a g i n g (7 views). Two technicians and 2 physicians i n t e r p r e t e d the results independently. The images w e r e r e v i e w e d by the o b s e r v e r s together. They SPECT was agreed that improved contrast of p a r t i c u l a r l y useful in e q u i v o c a l p l a n a r images. The a d v a n t a g e of S P E C T was c o n s i d e r a b l y less in o b v i o u s abnormalities. Occasionally, the p l a n a r a p p r o a c h was s u p e r i o r (improved s p a t i a l r e s o l u tion). S P E C T was the most time c o n s u m i n g p r o c e d u re: 65-75 m i n for QC, a c q u i s i t i o n and a n a l y s i s (planar: 30 min). Additionally, we f o c u s e d o n the r e l a t i o n b e t w e e n r e s o l u t i o n and c o l l i m a t o r - o b j e c t distance (d). P l a n a r studies of a b n o r m a l knees (n=10) r e v e a l e d that an i n c r e a s e of d by I0 cm (ie. d i f f e r e n c e b e t w e e n in v i v e S P E C T radius and p l a n a r d) m a d e 25% of the lesions undetectable. In v i t r o (line s o u r c e s / F W H M ) studies s h o w e d t h a t S P E C T ( d = p l a n a r + 1 0 e m ) had 23-95% less r e s o l u t i o n t h a n p l a n a r imaging. We c o n c l u d e that S P E C T of the knee s h o u l d be r e s t r i c t e d to cases in w h i c h p l a n a r s t u d i e s do not a l l o w an a c c u r a t e diagnosis, unless radius and a c q u i s i t i o n time (dual h e a d system) c a n be shortened.

M Y O C A R D I A L S P E C T : 1800 O R 360" O R B I T ? To a s s e s s t h e i n f l u e n c e of h a l f a n d full c i r c u l a r o r b i t s w i t h S P E C T a c q u i s i t i o n s , we e x a m i n e d a c y l i n d r i c a l p h a n t o m w i t h c e n t r a l (CLS) and posterior, e c c e n t r i c l i n e s o u r c e s (ECLS), at r a d i i of 14 to 24cm. H a l f o r b i t w a s d o n e a n t e r i o r (ANT) and p o s t e r i o r (POST). F u r t h e r more, a myocardial phantom (MP) w a s p l a c e d centrally and eccentrically in a t o r s o - l i k e tank. T h i s MP, c o n t a i n i n g T c - 9 9 m c o n s i s t e d of 8 c o n c e n t r i c annuli, a n d a 2cm ~ defect. Half o r b i t w a s d o n e A N T (-135 Q to +45°). T h e M P w a s also studied filled w i t h TI-201. Resolution w a s m e a s u r e d by t h e full w i d t h h a l f m a x (FWHM) of t h e l i n e s p r e a d f u n c t i o n ; c o n t r a s t b y the r a t i o of t h e E C L S a n d t h e C L S i n t e n s i t i e s in the axial tomograms. In t h e M P a x i a l slices, r a d i a l p r o f i l e s for e a c h a n n u l u s w e r e summed. To a s s e s s the e f f e c t of a t t e n u a t i o n , profiles obtained from both orbits were subtracted. F W H M r a n g e d f r o m 16 to 2 1 m m w h e n t h e r a d i u s i n c r e a s e d f r o m 14 to 24cm, for the CLS w i t h b o t h orbits. F o r E C L S w i t h 3600 a n d P O S T 180 ~ the v a l u e s w e r e s i m i l a r , b u t r a n g e d f r o m 30 to 3 5 m m w i t h A N T 180 °. The c o n t r a s t w i t h 3600 w a s 1.8; w i t h A N T and P O S T 180 ° I.I and 3.0, resp. The M P w i t h T c - 9 9 m or T I - 2 0 1 s h o w e d t h e l e a s t i n f l u e n c e of a t t e n u a t i o n w i t h 360 ° if l o c a t e d c e n t r a l l y ; w i t h 180 o if l o c a t e d e c c e n t r i c a l l y . T h e d e f e c t w a s s e e n b e s t w i t h 180 o, i r r e s p e c t i v e of location. C o n c l u s i o n : an o r b i t of 180 o i m p r o v e s r e s o l u t i o n a n d c o n t r a s t of n e a r b y objects, a n d m i n i m i z e s a t t e n u a t i o n effects.

TP-5K0-3

TP-5K0-4

A.R. van Ieperen, L.Kiebooms, L.Driesl+ens,P.Noyens~ G.Thys D e p a r t e m e n t of N u c l e a r Medicine, St 3ans Ziekenhuis, 3600 GENK~ BELGIUM

Alvarez I g l e s i a s G.J., S i e r r a Gonz~lez G., Sierra Gonzelez P., Ruiz G u i j a r r o J.A. CIC Y MP CARLOS I I I - Madrid ICE- Madrid

A P R A C T I C A L EVALUATION OF THE VALUE OF A FPASS STUDY COMBINED WITH A MIBI SPECT C A R D I A C STUDY

TECHNIQUES ASPECTS OF LYMPHOSCINTIGRAPHY (LS):

The purpose of this study was to d e t e r m i n e the clinical value of t h e e j e c t i o n value(EF) and i s o c o n t o u r i m a g e derived i r o m the FPASS d a t a , doing a c o m b i n e d FPASS MIBI SPECT c a r d i a c study. In 15 p a t i e n t s the relationship b e t w e e n EF m e a s u r e d with the FPASS t e c h n i q u e (RAO 10 °) and g a t e d v e n t r i c u l o g r a phy(LA0 40 ° ) was d e t e r m i n e d . Two d i f f e r e n t p r o g r a m s for det e r m i n g the EF ~f6m FPASS d a t a w e r e e v a l u a t e d . A n isocontour i m a g e was c o n s t r u c t e d f r o m the FPASS d a t a to d e t e r m i n e the a m o u n t of c o n t a c t i b i l i t y of d i f f e r e n t regions of the m y o c a r d i u m This i m a g e was e v a l u a t e d t o g e t h e r with the SPECT MIBI i m a ges in 15 p a t i e n t s u n d e r g o i n g r e s t or p y r i d a m o ] s t r e s s c a r d i a c tests. The linear r e l a t i o n s h i p b e t w e e n the t w o t e c h n i q u e s was d e t e r m i n e d : (FEF=Firts Pass EF; GEF G a t e d EF) Method I : FEF=0.82 GEF+ 0,90 (r=O.g~) Method II : FEF~0.91 GEF + 8 . 9 1 ( r = 0 . 8 7 ) These results i n d i c a t e t h a t absolute values of EF d i f f e r b e t w e e n the t e c h n i q u e s and c a r e must be t a k e n when using the s a m e c r i t e r i a for normal in the di£ferent techniques. Isocontour i m a g e s give valuable a d d i t i o n a l i n f o r m a t i o n of viable m y o c a r dium when doing a c o m b i n e d FPASS MIBI SPECT study.

Lymphoscintigraphy i s a very u s e f u l technique to study the lymphatic system. Since i t i s not widely used we t h i n k important t o communicate our experience. M and M: According to the i n j e c t i o n technique two groups were created among the 45 p a t i e n t s s t u d i e d ; Group i cons i s t e d in 10 p a t i e n t s who were i n j e c t e d in the second interdigital space. Group 2, 35 p a t i e n t s i n j e c t e d in the f i r s t i n t e r d i g i t a l space. I n j e c t i o n was made in the subcutaneous t i s s u e having a s p e c i a l care not to i n j e c ~ in hoards vessels. We used 9gmTc m i c r o c o l l o i d as trace~ which i s commercially a v a i l a b l e as a p r e c o l l o i d t h a t needed t o b o i l f o r 4 min. Volume was kept under 0.25ml t o avoid unnecessary inconvenience to the p a t i e n t . Dose was 6mCi in each f o o t . Early imaging was performed in 15 p a t i e n t s , to allow study o f the lymphatic channels, and delayed in the 45 p a t i e n t s to study ganglionary groups. RESULTS: There were no s i g n i f i c a n t v a r i a t i o n s in the v i s u a l i z a t i o n o f the lymphatic system r e l a t e d to the i n j e c t i o n s i t e . Early images demonstrate in 7 p a t i e n t s o b s t r u c t i o n o f the lymphatic duct. Deiayed imaging showed asimetry i n ganglionary group as a r e s u l t o f obstruction. DISCUSSION: Since i t ks not a w i d e l y used technique we b e l i e v e d i t is important t o show our experience. Our showed t h a t s i t e of i n j e c t i o n not cause s i g n i f i c a n t di~ f f e r e n c a unless the technique was not c o r r e c t . For a b e t t e r i n t e r p r e t a t i o n both e a r l y , and delayed imaging are needed.

691

Thursday, 5 September 1991

TP-SK0-5

TP-5K0-6

Z.H~z, N.~ak]i, A.G~rpe, Dept.of Nuclear Medicine, Istanhul Medica] Faculty, Capa 34390 Istanbul,Turkey.

H.Kranz, L.Lotritsch, R.Weller, E.MillerSchneider, W . E . A d a m Nuklearmedizin, U n i v e r s i t ~ t Ulm, Germany

QUALITY CONTROL OF THE GAMMA CAMERA SYSTEM

DIE DURCH~'O~tTNG DER MYOCARD-ECT MIT 201-TL UNTER BESONDERER BEROCKSICHTIGUNG VON QUALITATSKONTROLLE UND ADAQUATER DATENPI~ASENTATION

This quality control work is dons almost one year after the installation of the gamma camera according to NEMA and IAEA instructions. In the mechanical set-up check,it was found out that the base of the gantry wasn't hard enough thus causing vibrations and the head of the camera wasn't remaining para]el to the COR during the a c C ~ % i Q n ( a b o u t 4 mm). LEAP collimator had a diagonal hot bar artifact. All other performance specifications; intrinsic and system specie] resolutions, integra] and differen$ia] uniformities etc. were found quite larger than the worst case values. Software is controlled by proseasing the phantom data taken by the same type of the camera (Siemens ZLC 7500) working well. After reinstalling the gantry proper]y and the mechanical adjustment of the head, resolution was satisfactory and distortions were lost in the Jaszczak phantom images. Although qua]ity of the images highly increased after all this work, misdoing the ~nstal]ation and late doing the acceptance tests caused priceless ]oss of time and energy.

Die T i - 2 0 1 - S P E C T - U n t e r s u c h u n g ist eine nichtinvasive M e t h o d e zur D a r s t e l l u n g der Durchblutung des Herzmuskels. Ziel dieser P r e s e n t a t i o n ist es, aufzuzeigen, dab durch ein striktes Protokoll u n d s t a n d a r d i s i e r t e Kontrollen die Qualit~t u n d die R e p r o d u z i e r b a r k e i t der Unters u c h u n g s e r g e b n i s s e g e w ~ h r l e i s t e t ist. Dies setzt voraus: -f~r den P a t i e n t e n eine genaue A u f k l ~ r u n g u n d Vorbereitung, sowie eine stabile als auch bequeme Lagerung, evt. K o m p r e s s i o n der M a m m a mittels Brustband? -f~r die K a m e r a eine w6chentliche, sorgf~itige Qualit~ts~berpr~fung. Floodfieldund Center-off-Rotation-Studies, die in einen Camera-Configuration-File e i n g e s p e i c h e r t werden, m ~ s s e n b e i der R e k o n s t r u k t i o n ber~cksichtigt werden. -f~r die A u s w e r t u n g der Stress- u n d Redistrib u t i o n s a u f n a h m e n eine exakte Eingabe der Herzachse u n d A u s w a h l der Schnittbilder. - eine ~ b e r s i c h t l i c h e Dokumentation, b e s t e h e n d aus q u a n t i f i z i e r t e n P o l a r b i l d e r n sowie Aktivit~tsdarstellungen der Kurzu. L~ngs-Achsenschnitte in Stress u n d Ruhe im Vergleich. Der U n t e r s u c h u n g s a b l a u f w i r d yon der Patientenadministration bis zur B e f u n d d e k u m e n t a t i o n demonstriert.

TP-5K0-7 E.Miller-Sehneider, S.Mack, H.Kranz, M.Clausen, ~.E.Adam Nuklearmedizin, Universit~t Ulm, Germany

L.Lotritsch,

THERAPIE MIT FLUSSIGEN RADIONUKLIDEN - DARSTELLUNG DER VORGEHENSVEISE UNTER BERUCKSICII~rlGUNG DES STRAHLENSCHUTZES FOR DIE HEDIZINISCH-TECHNISCHE-ASSISTENTIN

Bei der Radiojodtherapie hat sich die Verwendung von Kapseln insbesondere aus StrahlensehutzgrOnden sehr bew~hrt. Bei anderen Therapien liegen die Radionuklide in der Regel in offener, flOssiger Form vor. Dies hat zur Folge, dab das betroffene Personal sich auf spezielle Vorgehensweisen und ver~nderte Strahlenschutzbedingungen einstellen muN. Zur Verwendung kommen u.a. Jod-131-Benzylguanidin, Yttrium-90 und Phosphor-32. Die Vorgehensweise kann bier wie folgt aussehen: - Vorbereitungen~ z.B. Proportionieren der Aktivit~t in speziellen Spritzen, Bereitstellen steriler Bestecke, Lagerungshilfen ffir die Kniegelenkspunktion, Lokalan~sthesie - Strahlenschutzmagnahmen, z.B. Plexiglas-Spr~tzenabsehirmungen bei Y-90 und P-32, Bleiabschirmung des Tragebeh~iters und des Perfusors bei IBG - Abfallentsorg, ung, z.B. Kanfilen- und blutkontaminierter Abfall zum separaten Infektionsmfill, brennbarer Abfall yon Betastrahlern nicht in Bleigef~gen sondern in speziellen Beuteln lagern (Vermeidung yon Bremsstrahlung) Entsorgung des Kniegelenkpunktates unter Ber~eksiehtigung der Kontaminationsgefahr. Dutch sorgf~itige und geeignete Vorgehensweise l ~ t sieh die Strahlenexposition bei der Vorbereitung und Anwendung flUssiger Radionuklide zur Therapie ffir die MTA auf ein Minimum reduzieren.

692

J. Mester, A. Makay

E. M~td, L. Csernay, A, Kuba, S. Madani,

Department of Nuclear Medicine, Albert Szent-Gy6rgyi Medical University, Kalm~r Laboratory, J6zsef Attila Un±versity, Szeged, Hungary. 3D PRESENTATION OF THE FOURIER AMPLITUDE AND PHASE. A NEW FAST DISPLAY METHOD FOR GATED CARDIAC BLOOD POOL SPET A new technique for the simultaneous 3D presentation of the amplitude and phase of the first Fourier harmonic is presented with the aim of obtaining detailed information about the ventricular motion in a relatively short time, from each angle of view of 3D space. Gated projection oimages were collected at 6 ° intervals over 180 , with 16 frames per cardiac cycle. Projection data sets were reduced to the images of the sine and cosine coefficients of the first Fourier harmonic and average blood pool. The images were reconstructed to 1 pixel (6mm) thick transaxial sections by filtered backprojection, using a Hamming filter. After reconstruction, transaxial sections of Fourier amplitude and phase were computed. The endocardial surface of the heart was reconstructed on the basis of the set of transaxial average blood pool sections (background cut-off 50% of the maximum voxel activity). The amplitude and phase of each surface point were determined on the basis of the corresponding transaxial sections and mapped onto the previously determined cardiac surface. The results are presented as the rotating 3D amplitude and phase being observed from a view perpendicular to the body axis of the patient. Selected images can also be analysed from an operator-determined angle of view. The processing time is about 12 min on an Amiga-3000-based nuclear medicine computer.

L.J. Boersma, E.M.F. Damen, R.W. DeBoer, J,V. Lebesque, R.A. ValdSs Olmos, C.A. Hoefnagel.

The N e t h e r l a n d s Cancer Institute, Amsterdam, The Netherlands THREE-DIMENSIONAL SUPERIMPOSITION OF SPECT AND CT DATA TO QUANTIFY RADIATION-INDUCED VENTILATION AND PERFUSION CHANGES OF THE LUNG, AS A FUNCTION OF THE LOCALLY DELIVERED DOSE.

In order to determine a c l i n i c a l d o s e - e f f e c t r e l a t i o n for radiation-induced lung damage, a p r o s p e c t i v e s t u d y has been s t a r t e d in p a t i e n t s t r e a t e d with mantle f i e l d i r r a d i a t i o n f o r M. Hodgkin. CT and d u a l - i s o t o p e (Tc-99m and Kr-81m) SPECT s c a n s o f t h e l u n g s a r e made p r i o r t o radiotherapy and 5 months a f t e r t h e s t a r t o f the treatment. To align t h e images of both e x a m i n a t i o n s , f o u r s k i n markers a r e used t o determine a l i n e a r t r a n s formation matrix. The r e s u l t i n g match i s v e r i f i e d by p r o j e c t i n g t h e C T - d e f i n e d lung c o n t o u r s on t h e SPECT images. Subsequently, the 3D dose d i s t r i b u t i o n is c a l c u l a t e d u s i n g CT d a t a and t h e r e s u l t i n g i s o d o s e s a r e superimposed on t h e SPECT images. Changes in p e r f u s i o n and v e n t i l a t i o n in i r r a d i a t e d r e g i o n s can t h u s be anal y z e d as a function of the l o c a l l y delivered dose. In 7 p a t i e n t s studied so f a r , t h e t o t a l p e r f u s e d lung volume calculated from the SPECT images showed an a v e r age reduction of 30~. The t o t a l v e n t i l a t e d volume decreased only by 10%. Visual inspection of t h e SPECT images shows t h a t t h i s reduction in volume can be cont r i b u t e d to a c o n s i d e r a b l e d e c r e a s e o f lung f u n c t i o n in r e g i o n s i r r a d i a t e d to a dose h i g h e r than 34 Gy. To q u a n t i f y these functional changes in d e t a i l , s o f t w a r e

i s c u r r e n t l y being developed. indicate t h a t the combined u s e o f CT and SPECT information i s an e f f e c t i v e method to e s t a b l i s h a d o s e - e f f e c t r e l a t i o n f o r p e r f u s i o n and v e n t i l a t i o n changes. In the f u t u r e , knowledge of t h i s d o s e - e f f e c t r e l a t i o n w i l l be used to optimize 3D r a d i o t h e r a p e u t i e treatment plans to minimize t h e damage t o lung t i s s u e . Our r e s u l t s

DL Bailey1,4, T Jones1, DW Townsend2, A Geissbuhler2, and M Defries3. 1MRC Cyclotron Unit, Hammersmith Hospital, London, UK, 2University Hospital of Geneva, Switzerland, 3Vrije Universiteit, Brussels,Belgium, and 4RoyalPrince AlfredHospital,Sydney,Australia. INITIAL STUDIES WITH A 3D POSITRON TOMOGRAPIt Acquisition of all possible lines-of-response (3D mode) in PET scanners after removal of interplane septa offers greatly improved sensitivity over conventional 2D techniques. 3D reconstructions demonstrate improved quality due to the increased sensitivity, which is maximal in the centre (axially) of the scanner. Implementation of this method has required development of new methods for (i) attenuation correction, (ii) normalisation, and (iii) calibration of the neuro-scanner (Siemens/CTI 953B). (i) Attenuation correction factors are generated by forward projection through the 2D attenuation reconsmactions to derive the unmeasured lines-of-response for the 3D factors. (ii) Normalisation is determined from a direct-plane sinogram with septa in place. Sensitivity factors are then generated for individual detectors rather than lines-of-response. The 3D nonnalisation factors are calculated from the product of any 2 individual detectors' sensitivities. (iii) To overcome the axial variation in sensitivity, interplane sensitivity factors adjust the total counts to produce the same result as a 2D study. Calibration by this method has resulted in a measured sensitivity of =2cps.lxCi-l.cc -1, although the true sensitivity in the centre of the scanner is 6-8 times greater. To date over 35 patients have had 3D PET studies with a variety of radiotracers. CBF activation studies (ivi H2150) have demonstrated selective foci for processing motion in the visual field in a single individual; in 2D this requires pooled data from 3 subjects to achieve statistical significance. Similar cognitive activation studies have reproduced activation centres for verbal fluency which previously required 6 subjects in 2D to achieve significance. Dynamic studies with ISF fluoro-dopa give significant improvents in SNR and striatal definition. Dynamic lSFDG studies in a single individual in both 2D and 3D demonstrate higher quality of timeactivity curves in the 3D dataset, which is important for modelling kinetic data. Statistical gains of between 3-8 fold are achievable with 3D methods, giving better quality, higher resolution reconstructions.

~

i N,~PRAND IN I,

M. LODI*,

M. P A M P O L I N I * * ,

DEPARTMENTS OF NUCLEAR MEDICINE, CHEST DISEASES*, SURGERY** AND PATHOLOGY***, S. A N N A H O S P I T A L A N D U N I V E R S I T Y , F E R R A R A (ITALY) IMMUNOSCINTIGRAPHY ~S) WITH lllIn AND 99Tcm L A B E L E D M o A b S IN T H E P R E O P E R A T O R Y S T A G I N G OF LUNG CANCER: PRELIMINARY RESULTS Evaluation of locoregional extension and lymphnQdal i n v o l v e m e n t , is indispensable in a e n e r m l n i n g t h e o p e r a b i ± i t y of l u n g can~er. CT and MRI show similar results for the nodes mainly based on their increased sizes. The Authors report the role of IS, specific method, in the preoDeratory assessment of this neoplasm_ utilizing e i t h e r l l l I n a n d 9 9 T c m l a b e l e d MoAbs. S i n c e O c t o b e r 1990 30 ISs on 28 p a t i e n t s , 24 males and 4 females (mean a g e 61), w e r e p e r zormea: all the patlents unaerwent surgery examination. The ~ i s t o l o g i c a l f i n d i n g s were: 6 adenocarci~omas, 4 s m a l l cells, 4 a n a p l a s t i c a n d 12 e p i d e r m o i d c a n c e r s a n d 2 p h l o Q i stic lesions. The surgical sp@cimens of £umours were Dositive on CEA-immunostaininq. The F ( a b ' ) 2 f r a g m e n t s of a n t i - C E A F 0 2 3 C 5 Mo/ib ~borin Biomeeica, Ita±y) were ±aDe±ea with lllIn in 12 e x a m i n a t i o n s a n d w i t h 9 9 T c m in 18 (2 p a t i e n t s r e c e i v e d b o t h i s o t o p e s ) . ISs w e r e performed at 1 h o u r , 3-4 d a y s a n d 6-7 d a y s w i t h I n d i u m a n e at I, 6 a n d 24 h o u r s w i t h Technetium, with planar and SPECT imaging. Only radiopharmaceutical with labeling efflc i @ n c y m o r e t h a n 90% w a s u t i l i z e d on IS. ± n a i u m - I S f i Q u r e s on t h e ~ u m o r w e r e 9 TP, 0 F P , 1 TN, 2 F N (100% s p e c i f i c i t y ; 81.8% sensiDilitv) a n d on t h e l y m p h n o a e s were 6 TP a n d 6 TN. F o r t h e T e c h n e f i u m t h e f i Q u r e s on t h e t u m o r w e r e 5 TPv 0 FP, 1 TN, 12 F N (spec i f i c i t y I00%; s e n s l b i l i t y 28.4%) a n d on the n Q a e s w e r e 3 TP, 0 FP, 8 TN, 6 F N (specif l q i t y 100%; sens i b $ 1 i t y 33.3%). Two p o s l t i v e ±naium-ISs resulnea negative on successive 9 9 T c m e x a m i n a t i o n , p e r f o r m e d w i t h i n 2 weeks. In the preoperative s t a g i n g of l u n g c a n c e r lllIn-IS showed high accuracy whereas 99TcmIS, a l t h o u g h its h i g h s p e c i f i c i t y , had a too low sensibility e l t h e r on t u m o r a n d i v m p h nodes assessment, f o r an u s e f u l a p p l i c a t i o n . The r e a s o n is p r o b a b l y d u e to l o w narget/not targe~ ratio caused by a very high cardiomed i a s t l n i c a c t i v i t y , sdill at 24 h o u r s scan.

R.P. Baum~, R. Bares24 u. Buell 2, J.-F. ~hatal 3, C. Cutter , 9" Knauss , R. Schm~d-Fablan ,~ J. Kretschko ,7R, Seneckowitsch-, D. Lange v, K. Scheidhauer ~Prankfurt, 2~achen, 3Nantes, Heidelberg, Cologne

4Birkenfeld,

5Munich,

PRE-CLINICAL AND FIRST CLINICAL EVALUATION OF A NEWLY DEVELOPED HAND-HELD PROBE FOR INTRAOPERATIVE DETECTION OF Tc-99m LABELLED COMPOUNDS IN NUCLEAR MEDICINE - A MULTICENTRE STUDY

Extended abstract will be published in the "Yellow Book" by Schattauer-Verlag.

G.N. Reddyl2 W.P. Melega 2, D2W. Chang 2, J.R. Barrio 2 M.E. Phelps , N. Satyamurthy IDivislon of Radiopharmacy, Paul Scherrer Institut, CH-5232-Villigen PSI, Switzerland Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, CA 90024, USA

EVALUATION OF BREAST CANCER BY POSITRON EMISSION (PET) USING F-18 FLUORODEOXYGLUCOSE (FDG). T.P. Havnie, E.E. Kim, W.H. Wong, D.J. Yang, R.S. Tilbury, G. Hortobagyi, D.A. Podoloff, S. Singletary, L.E. Misra, A. Zermeno, University of Texas M. D. Anderson Cancer Center, Houston, TX. TOMOGRAPHY

PET using F-18-FDG has been useful in the differential diagnosis of recurrsnt brain tumor from posttreatment changes. We have evaluated I0 patients with proven adenocarcinoma of the breast including 3 postmastectomy patients and one patient with fibrocystic disease. Three consecutive 20 min transaxial images of bilateral breasts and axillae using a Posicam 6.5 camera were obtained after intravenous injection of 8-10 mCi F-18-FDG. Images were visually inspected and correlated with mammographic, sonographic, and MRI examinations. Semiquantitative count density ratios were generated from the area of the tumor (peak count area or total tumor volume) and control (contralateral or adjacent area. All tumors demonstrated gradually increasing uptake of FDG with time. Maximum ratios of peak count to control areas in primary and metastatic tumors were 7:1 and 15:1, respectively. Total tumor volume ratios were 5:1 and 7:1, respectively. Three week follow-up studies following chemotherapy in 4 patients showed markedly diminished FDG uptake in rmlative quantity and rate. No significantly increased FDG uptake was seen in fibrocystic lesions. It is concluded that PET using F-18-FDG is helpful in staging and evaluating therapeutic response of breast cancer.

~-FLUOROMETHYLENE-4-[18F]FLUORO-m.~-TNYROSINE,

ENZYME-ACTIVATED, INHIBITOR OF MONOAMINE OXIDASE: NOVEL SYNTHESIS AND IN-VIVO PROPERTIES

Extended abstract will be published in the "Yellow Book" by Schattauer-Verlag.

P M KEMP, M A MACLEOD, A S HOUSTON, L JENKINS AND L TOMS DEPARTMENT OF NUCLEAR MEDICINE, ROYAL NAVAL HOSPITAL, HASLAR, GOSPORT, HANTS, UNITED KINGDOM

MAJOR

NORMALITY AND HMPA0 BRAIN SCANS - IS INTELLECT A FACTOR? A recent study I comparing HMPAO cerebral perfusion scans in 20 amatuer boxers and 41 hospital controls showed a significant difference between the 2 groups. A closer inspection of the data revealed that 58% of the boxers with Ordinary Level qualifications had a "completely normal" scan whereas only 25% of those with the lesser qualification of the Certificate of Secondary Education (CSE) had a normal scan. This findingprompted a retrospective analysis of the control data which noted a similar proportion of the hospital controls with Ordinary Levels who had a normal scan (60%) rising to 80% of those with Advanced Levels/degree (statistical significance p 40.02), It could thus be concluded that the original difference between boxing and control groups was a reflection of different intellectual ability and this finding has important implications in defining "normality" for HMPA0 cerebral perfusion scanning. P M KEMP, M A MACLEOD, L JENKINS, A S HOUSTON AND L TOMS. Cerebral perfusion in amateur boxers (Abst) N.Med.Commum.1991:12;279

v o n S m e k a l A.. S c h ~ f e r G.*, B i e r s a c k H.J. Dep. N u c l e a r M e d i c i n e , U n i v e r s i t y of Bonn, F R G *Dep.of Mech.Engin.,Tech.Univ. Clausthal, FRG ~N EXERCISE DEVICE FOR NUCLEAR M~GNETIC RESONIqNCE S T U D I E S OF THE HUMAN HEART The purpose of t h i s s t u d y w a s t o d e v e l o p a n optimized exercise device for cardio-vascular stress studies during Magnetic Resonance (MR) d a t a a c q u i s i t i o n . T h i s d e v i c e c o n s i s t s of n o n magnetic materials f a c i l i t a t e s d y n a m i c or s t a t i c e x e r c i s e of o n e s 21s~6~I or both legs by ~ ~ ~ 6 alternately pistons against an adjustable resistance in a closed, fluid f i l l e d s y s t e m (Fig.l). It is p o s s i b l e to b u i l d u p r e s i s t a n c e b y p u s h i n g and/or pulling. Adjustable pressure regulation v a l v e s a l l o w p r e s s u r e s u p t o , 1 0 bar, h y s t e r e s i s 5%. T h e s t r e s s c a n b e c a l c u l a t e d as p r o d u c t of p r e s s u r e a n d v o l u m e f l o w (P=p*V). V o l u m e f l o w c a n be c a l c u l a t e d b y p i s t o n aerea, s w e p t v o l u m e a n d cycle frequency (V=Ak*h*f) . T h e r e s u l t c a n b e converted in Watt. The patient is p l a c e d in s u p i n e p o s i t i o n in a s p e c i a l l y d e v e l o p e d u p p e r body support shell to avoid chest movements. The d e v i c e is s m a l l a n d e a s y t o m o u n t on t h e m a g n e t s table. O n t e n h e a l t h y v o l u n t e e r s , 31p S p e c t r o s copic Imaging studies during rest and exercise have been performed and the high energy phosphates peak ratios have been calculated and compared. This device allows exercise studies d u r i n g M R d a t a a c q u i s i t i o n a n d is a l s o s u i t i b l e for exercise studies during heart scintigraphy o r P o s i t r o n E m i s s i o n T o m o g r a p h y (PET).

and~

moving~