European Journal of N u c l e a r

Eur J Nucl Med (1987) 13:A1-A7

Medicine © Springer-Verlag 1987

Abstracts

I. Scientific Meeting of the Dutch Society of Nuclear Medicine November 15 and 16, 1985, Bunnik, The Netherlands Chairman: G. Samson Eur J Nucl Med (1987) 13:A1-A4

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CA 125: A TUMOR MARKER FOR GYNAECOLOGIC CANCER H,W,A, de B r u i j n , M.S, S c h i l t h u i s , M,J, Duk, H, Kooi, A, van Zanten, G,J. Fleuren end J.G, Aalders,

CLINICAL APPLICATION OF THE DETERMINATION OF SERUM TUMOUR MARKERS USING MONOCLONAL ANTIBODIES A. van Dalen Monoclonal antibodies may have advantage over polyclonal antibodles in determining substances in serum produced by malignant tumours, Elevated serum values of prostate acid phosphatase (PAP) and prostate specific antigen (PSA) indicate metastases of a prostate carcinoma. There is no signlficant clinical difference whether one uses polyclonal or monoclonal antibodies PSA has a somewhat hi~her sensitivity than PAP in diagnosis as well as in the followup. In breast carcinoma the sensitivity of CA 15-3 (determined by using two monoclonal antibodies) is higher than of CEA and TPA as proved by using ROC-curves. In the follow-up the sensitivity of CA 15-3 for metastatic disease is about 85% at a specificity of 95%. Individual examples will be used to demonstrate the importance of the determination of CA 15-3 when changing therapy, especially in sutuations where bone selntigraphy and X-ray investigations give un equivocal results. CA 125 is an excellent marker to determine whether a debulking operation and combined chemotherapy is effective in ovarian cancer. The decline of CA 125 values should be optimal (even within the "normal area") if not, second look operatlons will always reveal metastatic disease. The hypothesis will be discussed that this pattern recognition can make second-look operations redundant and may influence therapeutic regimes.

CA 125 i s a high molecular weight glycoprotein, produced by e p i t h e l i a l ovarian tumors. I t can be measered with a redioimmunoradiometric assay, using the monoclonal antibody OC 125. In healthy women we found extremely high levels in in the c e r v i c a l mucus (median 65,500 U/ml, n=23), but normal levels were found in blood samples ( < 3 5 U/ml), We conclude that CA 125 is a normal secretory product o f the female genital t r a c t , Although not tumor s p e c i f i c , serum CA 125 levels are very useful f o r monotoring the e f f e c t of therapy in patients with ovarian: endometrium and tubal cancer. We measered high levels o f CA 125 in cyst f l u i d s from e p i t h e l i a l ovarian tumors (median 24,600 U/ml: n-25). Benign tumors and also mucinous tumors produce CA 125. Serum levels were not related to cyst f l u i d CA 125 concentrations, but were dependent on the presence or absence o f i n f i l t r a t i v e growth of the primary tumor. Pre-operative serum levels were elevated in nearly a l l patients with ovarian cancer (42/45). Levels up to 4,500 U/ml were found in endometrial cancer, 27 of I I 0 showed raised l e v e l s of CA 125. E x t r a - u t e r i n e tumor extension and the presence o f tumor c e l l s in vessels correlated strongly with the presence of elevated serum l e v e l s . A l l patients with tubal cancer (n-6) had raised levels o f CA 125. Increasing levels preceeded the c l i n i c a l discovery o f tumor relapse in patients with ovarian cancer ( 1 5 / ] 9 ) , in patients with endometrial cancer 5/12 and in tubal cancer (2/2) with e median lead time of 3, 1.8 and 4 months r e s p e c t i v e l y , Serum CA 125 levels are a sensitive indicator of intraperltoneal metastases, but not f o r local dlsease recurrence on the vaginal apex, Department o f Obstetrics and Gynaecology, U n i v e r s i t y Hospital , 9713 EZ Gronlngen, Oostersingel 59. The Netherlands.

Department of Nuclear Medicine, eleuland hospital, P.O. Box 1098, SSO0 BB Gouda, The Netherlands.

< r o o n . J.G. Chin, E . K . J . A.E. van V o o r t h u i s e n

Pauwels,

and

Congenitally corrected transposition [CTT) of the g r e a t v e s s e l s is an u n c o m m o n a n o m a l y u s u a l l y d e t e c t e d in c h i l d r e n b e c a u s e of associated severe cardiac malformations, W h e n t h e s e are a b s e n t , p a t i e n t s m a y be hemodynamical!y normal, but associated cardiac abnormalities are u s u a l l y p r e s e n t in COT, l e a d i n g to s y m p t o m s in a d u l t h o o d . W h e n OCT is s u g g e s t e d in an a d u l t , d i a g n o s i s by m e a n s of u l t r a s o u n d m a y be d i f f i c u l t . Radionucldde angiocardiography [RA) is a simple, noninvasive m e t h o d by w h i c h to d i a g n o s e CCT. We f o u n d c o n s i s t e n t morpheio~ic scinti~raphio r e s u l t s in 13 p a t i e n t s w i t h p r o v e d CCT, ~ e a d i n g to e s t a b l i s h m e n t o~ r e l i a b l e d i a g n o s t i c criteria. In all instances o~ s i t u s s o l i t u s , the a o r t a a s c e n d s and d e s c e n d s on t h e l e f t w i t h vertical orientation. In the e a s e o~ situs inversus, the a o r t a a s c e n d s and d e s c e n d s on t h e r i g h t w i t h v e r t i c a l o r i e n t a t i o n . O u r c r i t e r i a are i n d e p e n d e n t of the s i t u s and c a r d i a c p o s i t i o n , unlike e a r l i e r r e p o r t s by o t h e r s . We b e l i e v e i m a g e s o b t a i n e d in the a n t e r i o r p r o j e c t i o n are s u f f i c i e n t f o r the s t u d y . T h e p r a c t i c a l application of RA s t u d y in p a t i e n t d i a g n o s i s is d e m o n s t r a t e d , giving special attention to p a t i e n t s r e f e r r e d b e c a u s e of s i t u s s o l i t u s and d e x t r o o a r d l a , in w h i c h CCT is K n o w n to be p r e s e n t in 50% of c a s e s . Oepartments of O i a g n o s t i c Radiology and Cardiology, University Hospital, Rijns bur~erweg ID, 2 3 3 3 AA L e i d e n , N e t h e r l a n d s .

A2 4 LOCATING ELLIPTICAL OBJECTS J.A.K. Bloklandj A.M. Vossepoel, and A.R. Bakker

IN SCINTIGRAMS E.K.J. Pauwels,

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A ~IME-SPACE MAIRIX DISPLAY TECHNIQUE FOR THE ASSESSMENT OF URETERAL PERISIAL51S C. Sterk,

THE ACR-NNMA PROPOSAL FOR IMAGE COMMUNICATIONS: IMPLICATIONS AND OMISSIONS CONCERNING IN-VIVO NUCLEAR MEDICINE C.N. de Graaf

E.G.M. D'haene and E.J. van de Vusse.

Finding edges of partly invisible objects, like Ti-201-scintigrams of the ischemie left ventricle (LV), is only possible when some a priori knowledge of the shape of the object is incorporated in the edge detector. We have adapted the Hough transformation (U.S. Patent 3.069.0654, Dec.1962), using the method described by Shapiro (Pact.RacE., Vol i0, 1978: 129-143) and have developed an algorithm to find elliptically shaped objects. From the equation of the ellipse and its derivative the length of both axes cmn be computed by using only local information of an edge point: its coordinates related to the center of the ellipse and the direction of its gradient related to the orientation of the ellipse, Because of noise not all estimates lead to the same result. From the 2-D-histogram of all estimmtes, the most frequent estimate can be computed. The frequency of occurrence of this estimate is used as a measure of the quality of the estimate. This quality number in turn is maximized by changing the coordinates of the center and the orientation of the ellipse. Applying the algorithm to models with different signal-to-noise ratios, it has shown its feasibility. Especially in our configuration (MDS-A2) it requires a lot of CPU time, hut because of the parallel nature of most of the computations, this problem can be reduced by using an array processor. The method can be easily extended to three or more dimensions, allowing real 3-D-edge detection in SPECT. The ~Igorithm can also he used in combination with other parametric models. The main disadvantage is the modelling step, in which only parametric models with a small number of parame tats are allowed. Not every object can he modelled in this way. The method can he of value in delineatlon of the LV, especially in programs for quantifying the d i s t r i b u t i o n of TI-2Ol whithin the myocardium.

The knowledge of the physiology and pahbophysiofogy of the human ureter has remained limited, probably due to the fact that the available techniques are invasive and non-physiological or have a high radiation burden for the patient. We thereFore believe that there is a place for a ne~ alternative to study the motility of the ureter in health and disease. Muller-Schauenburg published a ne~ nuclear medicine technique for this purpose (Athempto Verlag TObingen, W-Germany, 19B3). We based our ~ork on his experiences. AFter the injection of the Farmacon, 0.8 - 1.0 mCi 1-125 Hippuran (not contaminated with 1-124) ~e performed a routine split renal function study ~ith a high framerate (1 frame per 2 s.). A program has been ~ritten For the MDS-A2 system ~hich constructs a parametric image From that data. Over each ureter starling with the renal pelvis and ending in the urinary bladder 6-12 Regions of Interest (ROI) are placed in adjacent position. For each ROI a time-activity curve is generated. Next all corresponding points of the 6-12 curves are sorted and aligned in vertical columns resulting in a long band of data. The length of this band is such that if is impractical to display. That's why it has to be folded in a 64x64 matrix in segments of 60 elements each. The temporal information is displayed in the X-directzon (frame number) and the spatial information in the Y-direction (ROI-number~. Various contrast enhancement techniques are available. Peristaltic events (spindles) appear as oblique lines of increased activity running From the top (renal pelvis) to the bottum (bladder). Spindle velocity, spindle frequency and regularity of the spindle rhythm can easily be do

Department of Diagnostic Radiology (Div. Nuclear Medicine)~University Hospital,Rijnsburgerweg 10~ 2333 AA Leiden, Netherlands.

Department of Nuclear Mediezne, Gemeenteziekenhuis Dordreeht, Bankastraat 57, 5312 GA Dordreeht, Ihe Netherlands.

University Hospital of Utrecht, room 73038, Catharijnesingel 101, 3 5 1 1 G V Utrecht, The Netherlands.

cumented For each ureter. Pathologzeal p e r i s t a l tie patterns can be demonstrated. Some elinzcal examples ~ill be sho~n during the presentation. The clinical role of this technique has to be further defined; the First results are intriguing and promising.

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A COMPARATIVE

STUDY OF INTRAVENOUS DIGITAL SUB-

TRACTION ANGIOGRAPHY

(DSA) AND VENTILATION/PER-

FUSION SCAN (V/Q) IN PATIENTS SUSPECTED OF PULMONARY EMBOLISM

(P.E.).

JF Vermijlbe~geh,

DB Piers, CJJ Westermann and JWLudwig. The results of DSA of the pulmonary vessels

Fig. I . Results of DSA and V/Q in 97 patients suspected of pulmonary embolism V e n t i l a t i o n / p e r f u s i o n lung scintigraphy DSA of the Normal and Indetermin- High and pulmonary very low ate very high vessels probability probability No signs of P . E .

31

0

3

4

2

2

0

5

50

were compared with the results of V/Q scans in a prospective

study in 102 patients

suspected

of P.E. The aim of the study was to determine wheter DSA could more accurately demonstrate P.E.

In 1984 the NEMA (National Electronics Manufacturers Association) and the ACR (American Colle~e of Radiologists) have jointly proposed a set of protocols for the transportation of digital diagnostic images trough networks. These protocols are meant to be universal and transparant to all medical imaging modalities, as well as to the different manufacturers' brands of imaging, processing, displaying, mnd arehiving equipment. The document that defines these protocols, as well as hardware and software implementations~ are cryptical indicated by "ACR-NEMA" or "the ACR-NEMA stmndard". It turns out that a substantial part of the protocols is useful for the digital dmta management in a Nuclear Medicine department, even if there is no network environment. We have implemented the socalled session and transport layers of the "ISO-OSl-model" (a layered model for data communication mechanisms) according to the ACR-NEMA standard in our department for transportation of image data via serial media. In doing so, we noticed several problems and even omissions in ACR-NEMA, specifically related to the nuclear medicine modallty.

compared to V/Q, especially

obstructive

pulmonary disease

(COPD) patients

and secondly to find out if a combined strategy of DSA and V/Q was able to decrease the need for conventional

catheter angiography.

DSA studies were nondiagnostic, motion artefacts

13/102

5 due to severe

and 8 studies because of a

doubtful outcome.

0nly intraluminal

filling

defects or arterial vessel cuLt-off with parenchymal perfusion defects were considered positive of P.E., parenehymal

perfusion defects

alone were considered doubtful concerning F.g. V/Q scans were classified according to giello's classification.

7 V/Q studies

tic due to indeterminate the comparable studies studies was the same. were contradictory,

Departments

Positive signs of P.E.

SINGEL PHOTON EMISSION TOMOGRAAND OTHER BRAIN DISEASES E.A. de Brufne, M. Limburg, A. Vyth, J.B. van der Schoot

Thallium 201 chloride is not able to pass the bloodbrainbarrier. A lipophilic complex is formed if Thallium 201 is bound to diethyldithiocarbamate (Ti201-DDC). Vyth et al (Pharm.Weekbl.Sci ~,925-930, 1983) have demonstrated that this complex is able to pass the intact bloodbrainbarrier. De Bru[ne et al (J. Nucl. Med. 26, 925-930, 1985) reported in a comparative study on TI201DDC with Ii23-amphetamine that the former is a suitable radiopharmaceutical for measurement of cerebral bloodflow in the rabbit. Due to the immediate fixation of T1201-DDC in the brain during virtually only the very first passage, local activity reflects blood perfusion. The radiopharmaceutical may he considered as being a chemical microsphere. The following conclusions were made in a first clinical study employing a rotating gamma caMera and the Harvard muitidetector brainsystem in human. The uptake of TI201-DDC is partially functional: if injected during closed eyes a lower uptake is found in the occipital lobe. Ischemic defects are generally larger on TI201DDC SPECT scan than on a CT-scan. In Alzheimer disease a lower uptake is found in the parieto-occipital region as has been described previously employing PET scintigraphy and I i 2 3 - a m p h e t a m i n e SPECT. ~f injected during the epileptic fit an increased uptake is f o u n d in the region of the focus.

were nondiagnos-

outcome.

In 81/97 of

the outcome of both In 3/97 cases the results

follow-up studies revealed

a false-positive V/Q scan in I and probable fals-positive

Doubtfu]

in chronic

201 Thallium-DDC PHY IN ISC~EMIC van Royen, J.F. T.C. Hill , and

DSA studies in 2 (fig.l).

of Nuclear Medlcine,Radiology

Pulmonology. St.Antonius Hospital,F.O.Eox Nieuwegein, The Netherlands

and 2500,

Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.

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STUDY ON HAEMODYNAMIC AND SEMENQUALITY CHANGES IN VARICOOELE PATIENTS. H.Y. Oei, W.P.Th.M. Mald, J.W. Arndtp B.L.R.A. Coolsaet t J. Kremer.

REGULATION OF GASTRIC EMPTYING IN MAN:POSSIBLE ROLE FOR SECRETIN J.H,Kleibeuker,H.Beekhuis, D.A.Piers, g . B . S c h a f f a l i t z k y de Muckadell Previous studies suggest that s e c r e t i n at physiol o g i c plasma concentrations retards g a s t r i c emptying of liquids.We studied the possible role of secretin in the regulation o f g a s t r i c emptying of s o l i d food in 10 healthy s u b j e c t s , A f t e r ingestion of a g9m-Tc-colloid labeled pancake r a d i o a c t i v i t y w i t h i n the stomach was measured continuously during 1 hour using a dual headed 9ammacamera.Gast r i c content o f r a d i o a c t i v i t y was calculated as the geometric mean of a n t e r i o r and p o s t e r i o r counts in adequate regions o f i n t e r e s t . G a s t r i c emptying was expressed as the h a l f time (T~) of the r e s u l t i n g curve Subjects were studied 2 or 3 times on separate days:(1)with i n f u s i o n of saline (n=lO);(2)with i n t e r m i t t e n t infusion o f s e c r e t i n , during 3 periods o f 10 min at a dose o f 7.6 pmol/ kg.hduring each p e r i o d ; ( 3 ) w i t h continuous i n f u sion of secretin a t a dose o f 6.6 pmol/kg.h.Tests were done in random order.B5 min p r i o r to the meal 400 mg cimetidine was given i .v. to i n h i b i t acid secretion and so to prevent endogenous secr e t i n release. RESULTS Both during i n t e r m i t t e n t and continuous i n f u s i o n o f secretin g a s t r i c emptyingwas retarded s i g n i f i c a n t l y as compared to saline infusion (paired t-test,p
RELATIONSHIP BETWEEN SYMPTOMS AND GASTRIC EMPTYING IN BILLROTH II (RII) PATIENTS. A.J.P.M. Smout, L.M.A. Akkermans, J.M.M. Reelers, F,G. Pasma, N.Y, eel, and P. Wittebol.

Varicocele is a ~ell defined pathology, ho~everp the underlying ethiology is not yet established. The aim of this study is to clarify the h a e m ~ dynamic of varicoeele. In the first part of the study the reliability of the varlcocele scintiRraphy was assessed by comparing with the results of phlehography in 104 patients. Significant correlation was found between the velocity of the retrograde flow (RF) in the left testieular vein (LTV), the size of the varieoeele (SV) and the diameter (DM) of the LTV determined on the phleboRram. In the second part of the study we make the assumption plausible that in upright compression on LTV is more severe than in the supine position by measuring the pressure gradient (PG) between the left renal vein and the eaval vein. In 3& patients the PC in semi-erect position (mean 7.8 mmHg) is significantly hi~her than in the supine position (mean 3.8 rm~Hg). Further, significant correlation was found between Pg in semi-erect position and the DM of LTV, the SV and the velocity of RF assessed By seintigraphy. Rased on these two studies we defined the vat±cocole as a condition in which the valves in the LTV are absent or there is a renogonadal bypass, ~herehy the severity of the left renal vein eom7 press±on in the (semf-)erect position determining the velocity of the RF in the LTV and the SV. In the third part of the study the change of semenquality after treatment of the varieoeele was studled in 33 patients. No correlation was found between the change of semenquality~ the SV and the DM of LTV. However, our data suggest that patients showing a rapid RF in the LTV have more chance of improvement of the semenquality after treatment of the vat±cocole than those with no RF.

TABLE

saline

n=9 interm, secretin

T½(M+SEM) 52+4 (min

108+19

n=4 saline 65+6

contin. secretin 171+20

Dept. Gastroenterolgy,University Hospital ,g.O.Box 30.001, 9700 RB Groningeo, the Netherlands

Institute of Nuclear Medicine, State University Hospital, Catharijnesingel i01, 351] GV Utrecht, The Netherlands.

Gastric emptying of 9SmTc-labeled solid (pancake) and semisolid (porridge) meals was studied in 34 BII patients, operated because of duodenal ulcer (DU) disease, in 16 healthy subjects, and in R0 OU patients. Semisolid meal: In health, emptying started after a lag phase of 4.8±1.4 min. The lag phase was significantly shorter in DU pts (O.9i0.4 min) and absent in gII pts. Emptying followed a linear pattern in health and DU, but was biphasie in Rll pts, with a rapid rate in the flrst 5 min. BII pts with postcibal symptoms (n=iR) had signifimantly faster initial emptying (10,9±1.O %/min) than asymptomatic patients (4o1±0.8 %/min, n=iB). Positive correlations were found between the rate of initial emptying and the scores for early postprandial vasomotor symptoms (p~O.O01), epigastrie fullness and nausea (pKO.01% and vomiting (p<0,05). Post±nit±el emptying in the symptomatic BII pts (O.54±O.ll%/min) was slower than in all other groups (1.11±O.O7 %/min). Solid meal: The duration of the lag phase was 17.6±2,5 min in health. Both asymptomatic and symptomatic BIl pts had shorter lag phases (6.4± 0.5 and 8.6±1.3 min), but DU pts had comparably short lag phases (3.5±0.8). The rate of emptyin K was higher in DU (1.4S±0.15 %/min) than in health (l. OR±O.i3 %/min). Emptying was slower (p~O.Ol) in the symptomatic RII (0.47±0.08 %/min) than in the asymptomatie pts (O.80±0.12 %/min). Postprandial epigastric fullness and nausem were more severe as emptyin~ was slower (p~O.05). Conclusions: The major abnormality after RII resection is an increased initial emptying rate of sam±solids, correlating with symptoms of the early dumping syndrome. Emptyin K of a solid meal (taken without liquid) is not accelerated by BII resection it is even slower than in unoperated DU patients. Results of emptying studies in RII pts can be misinterpreted when the existence of a lag phase is not acknowledged and DU patients are not used ms controls. Depts. of Surgery and Nuclear Medicine, University Hospital Utrecht, Cath~rijnesingel i01, 3511 OV Utrecht, the Netherlands.

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SCINTIGRAPHY WITH 9gm-Tc-DIPHOSPHONATE AND ggmTc-PYROPHOSPHATE IN AA AND AL AMYLOIDOSIS. S. danssen and D.A. Piers

RADIAT]ON ULCER DUE TO INADVERTENTEXTRAVASAL INJECTION OF Tl-201. DOSIMETRIC CONSIDERATIONS. D.A. Piers, L.H.H.M. Drlessen, I.F. Brown, and H. Beekhuls.

SPECT IMAGING W I T H 1 - 1 2 3 , VARIOUS ROUTES F . H . v a n Weeren

Whole body seintigraphy with 99m-Tc-diphosphonate iTc-MDP) and 99m-Tc-pyrophosphate (Tc-PYP) was performed in 9 patients with systemic AA and 9 patients with systemic AL ~yloidosis. The purpose of this study was firstly to establish the efficacy of "bone-scanning" in demonstrating AA and AL amyloid deposits and secondly to determine the relative efficacy of Tc-MDP versus Te-PYP. The results of scintigraphy were compared with the results of clinical and histological studies, Scannin B with 99m-To-labeled phosphates appeared to be a sensitive non-invasive screening test for the extent and the distribution of organ involvement in both AA and AL amyloidosis. However, echocardiography seems to he more sensitive for demonstrating amyloid eardiomyopathy than scintigraphy. Tc-MDp images showed a better contrast than Te-PYP images, although there was no difference in the extent or the intensity of soft tissue uptake. In AA ~ y l o i d o s i s nephr opathy dominates the clinical scene; the saint±graphic pattern of organ involvement, however, appeared to be multisystemie, which is compatible with the histological distribution of ~/nyloid. The amyloid affinity for Tc-MDP appeared to be due (in vitro) to the presence in amyloid deposits of calcium bound to the glycoprotein AP, which is a eom]non constituent of all forms of amyloid.

A patient is presented with an ulcerous lesion in the l e f t elbow fTexure. Three years before T1-201 stress myocardlal scintTgraphy was performed. A f t e r injectTon of 3 mCi T1-201 i t became clear that most of the t r a c e r was administered extravenously. One week thereafter a red

The p u r p o s e of this study was to establish: i. The e f f e c t of the collimators on detectability. 2. The e f f e c t of t h e 1-123 p r o d u c t s available in t h e N e t h e r l a n d s o n SPECTimaging.

Department of Internal Medicine, University Hospital, 0ostersingel 5g, 9713 EZ, Groningen, The Netherlands.

infiltrated area was present at the site of the injection, which disappeared after conservative treatment. Three years later the lesJon recurred: a 3 x 4 cm sized reddish-brown solidly infiltrated plaque w~th a central round, punched-out leslon was present ~n the left elbow flexure. Diagnosis: radiatlon Tnduced ulcer of the skin after extravasal injection of TI-201. Skin grafting was performed. Estimating the radiation dose at the inject~on site two models can be used: (I) complete retention of the tracer at the injection site, and (2) disappearance from the injectTon site at a rate as found in experimental animals (Castronovo et al. 1984): retention at 30, 60 and 240 min respectively: 70, 64 and 47%. Assuming an infiltrated trssue amount of I gram in the first proposition a dose of 25000 rad can be calculated. In the second case a dose of 3300 rad is found. Probably our patient received a dose somewhere in between these two values. Conclusion: inadvertent extravasa] injection of TI-201 can lead to a local radiation dose hrgh enough to induce a radiation ulcer. Castronovo FP, McKusJck KA, Strauss HW. Oosimetric implications of the infiltrated injection. J Nucl Ned 1984; 25: P40. University

Hospital,

Groningen,

The Netherlands.

PRODUCED VIA

We u s e d 1 - 1 2 3 - n u c l i d e s o b t a i n e d b y two established production m e t h o d s and b y one which was introduced recently. Using a c y l i n d e r phantom homogeneously filled with activity, pictures were taken with a rotating gamma-camera. This enabled a comparison of three p a r a m e t e r s . The 12mm s l i c e s were j u d g e d i n d e p e n d e n t l y by t h r e e p e r s o n s . The b e s t r e s u l t s were obtained with a medium energy (300KeV) collimator independent of the radionuclidlc impurities. The Comptons o f t h e h i g h e n e r g y peaks o f 1-123 t u r n e d o u t t o be strongly biased a g a i n s t t h e low e n e r g y collimators. SPECT-imaging r e s u l t s with t h e 1-123 (p~2n) (new) production method are comparable to those with 1-123(p,Sn) where as the standard method 1-123 (p,2n) clearly shows a reduced detectability. Nuclear Department. Oistrict Hospital "Het Nieuwe S p i t t a a l " , Ooyerhoekseweg 8 , 7e31 SB W a r n s v e l d , t h e N e t h e r l a n d s

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16

PEROPERATIVE MONITORING OF CATHETER PLACEMENT IN THE NEPATIC ARTERY WITH Kr-81m. H.Y. eel, E.A. Runhaar, L.W.M. Janssenp J.P. Neijt.

STIMULA3ING EFFECT OF CO COMPOUND ON CELL LABELLING ESPECIALLY IN PRESENCE OF RESIDUE. W.Th, Goedemans, A.A. van Dulmen

When regional hepatic chemotherapy is administered via an implantable drug-delivery system for the treatment of liver metastases, extrahepatic perfusion must he avoided. Te-99m macro aggregated albumin (MAA) imaging has been applied to cheek the c a t h e t e r position postoperatively. Sinae the use of ~ for peroperative control of catheter placement has the disadvantage that repeated images can only be made with the subtraction technique, we image the perfused area peroperatively with 12mCi Rh-81/Kr-Blm as liquid generator (Cygne, gindhoven). The short half-life of Kr-gIm makes the use of repeated imaging possible. Preoperatively, Tc-99m colloid scans were made. Peroperatively, after proper placement of the catheter~ the Kr solution was infused via the catheter at a rate of 3 ml/min. A portable gamma camera was ased to obtain anterior and riEht-lateral views. Postoperatively, MAA scans were performed. Liver scans were obtained in this way in 5 patients. To determine the catheter position, the perfused areas on the Kr and colloid scans were compared. If the catheter position is correct, the Kr scan images only the liver and the catheter; a lateral view is therefore required to image the area below the catheter. In m o s t of the patients the distribution of Kr is not the same as that of MAA, however, due to the fact that Krypton scintigraphy can delineate the liver adequately it is suitable for peroperattve monitoring of the position of the hepatic-artery catheter. Institute of Nuclear Mediaine~ State University Hospital, Catharijnesingel 101~ 3 5 1 1 G V Utrecht The Netherlands.

17 OR CO GENERATING BY InRIlI-FHOPOLONATE, SIGNIFICANT PLASMA M.M.Th. de Oong, and

Earlier comparisons between tropolone, 2 meroapbopyridine-l-o×ide (mere) and o×ine showed no significant differences in cell labelling ability. Tropolone and mere were, as oxine, pobent cell labelling agenbs, but not better. However, carbon dioxide and a carbon dioxide generating compound diethyl pyrocarbonate markedly improved the cell labelling ability in plasma of firopolone and mere. In case of oxine bhis improvement was less distinct. Theoretical aspects of the CO cell labelling stimulating effect were dlsoussed in terms of inbra and extra cellular binding capacity of transferrin and lactoferrin with iron (indium). Compared bo o×ins and mere, tropolone behaved favourably with respect to inhibltion ef leukocyte migration under agar. .

2

.

THE EFFECT OF MANUAL PERCUSSION ON THE }[UCOCILIARY CLEARANCE IN PATIENTS WITH CHRONIC AIRFLOW OBSTRUCTION AND EXCESSIVE TRACHEOBRONCHIAL SECRETION C.P. v.d. Bchans, D.A. Piers and D.S. Postma The purpose of this study was to evaluate the effect of manual percussion, both as a single procedure as well as in combination with postural drainage, breathing exercises and coughing. Nine patients with clinically stable Chronic Airflow Obstruction (C.A.B.) and excessive traeheobronohial secretion underwent three different protocols of physical therapy on three different days. During the three protocols measurements of mucocillary clearance were taken during 50 minutes, using an inhaled radioaerosol technique. Baseline lung function was comparable on the days of measurement. The first protocol was applied with the patient in a horizontal position. Manual percussion was applled during 1O minutes. Nucoeiliary clearance was significantly increased during this period as compared to the period when the patient was at rest. The second protocol was applied with the patlent in a 20 headdown posltlon. Durlng 20 minutes manual percussion was applied in combination with coughing and breathing exeercises. Mucociliary clearance during the second protocol was significantly increased as compared to the first protocol. The third protocol was the same as the second, however, without percussion. There was no signifleant difference between the mucociliary clearance during the third and the second protocol. From this study it is apparent that manual percussion is a relatively ineffective procedure in patients with D.A.0. but may be useful when the patient is not able to cough and cannot assume the position of postural drainage. •

Nallinckrodb Diagnostica (Holland) B.V., P.O. Box 3, 1755 ZG Patten, The Netherlands

.

o

.

Departments of Physical Therapy, Pulmonary Disease and Nuclear Medicine, University Hospital, groningen, The Netherlands.

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19

HEPATOBILIARY STUDIES IN DUBIN-JOHNSON AND ROTOR SYNDROME D.A. Piers, J. Jager, C.M.A, Bijleveld and H. Beekhuis

SUBTRACTION SCINTIGRAPHY AND ULTRASOUND IN HYPERPARATHYROIDISM C.J.L.R. Vellenga, F.H.B. Tuynman, and H. Waller

Dubin-dohnson (DJB) and Rotor syndrome (MS) are inheritable disorders characterised by chronic (conjugated) hyperbilirubinaemia. In DJS the transport From the hepatocyte into the bile is impaired. In RS the defect is in the transport and storage of organic anions from the plasma in the liver cell. While modern g9mTo-cholescintigraphic tracers give high contrast images in moderate jaundice, evident abnormalities are encountered in DJS and MS. We studied kinetic sointigraphic data in a patient with UJS (typical BSP curve and coproporphyrin excretion) and a patient with RS (typical eoproporphyrin excretion and normal liver biopsy). Results were compared with findings in i0 patients (C) with normal hepatobiliary status, studied For bile reflux gastritis. After i.v. injection of 99mTe-disofen 6O x i min images were obtained over the liver and heart region. Blood samples were taken at 2,5,10,20,30,45,60,90 and ig0 min. Results: In the DJS patient fast and intense uptake in the liver was found, but the parenohymal washout was delayed: T~ 150 min, in C 24 min (mean) + 7 min (i SD). Blood clearance was moderately delayed: 2g% present at 60 min (in C < 10%). The RS patient showed no liver uptake, the tracer was excreted by the kidneys. The liver curve was similar to the heart and the blood clearance curves. At 60 min 50% of blood activity Was still present. These findings are compatible with the underlying pathophysiological disturbances in DJS and MS. Conclusion: (i) dynamic cholescintigraphy might be helpFull in differentiating DJS From RS (2) unexpected Finding of the patterns described in case of slight conjugated hyperbilirubinaemia should raise the possibility of DJS or MS.

In 13 patients, suspected of primary hyperparathyroidism, scintigraphic evaluation was performed after injection of 2 mCi 99 m Tcpertechnetate and 2 mCi 201 Tl-chloride. Simultaneous dual channel acquisition avoided movements artefacts. Using an A2-computer (MDS) subtraction (T1-Tc) and ratio (T1/Tc) images were created. In 5 patients scintigraphic localization of 5 adenomas (150-7000 mg) appeared to be correct at operation; there were 3 falsepositive seintigraphic findings. The remaining 8 patients were not operated: some scintigrams unequivocally showed adenomas, others offered the following problems of interpretation: I) small abnormalities of the subtraction, which did not allow differentiation between statistical scatter and small adenomas; because the scale of the subtraction image was equalized to the max. difference in counts between T1 and To, the window of this scale became very narrow and consequently the contrast too large, if the max. difference was small; sometimes the quantitatively more precise ratio-image offered more information; 2) symmetrical abnormalities, probably being artefacts; 3) abnormalities caused by thyroid nodi. Ultrasound was performed in B patients using a Technicare EDP 1200 scanner and a 7.5 MHz probe. Only the 7000 mg adenoma was found, in the other cases only a dubious abnormality was seen in retrospection. Conclusions: I) Scintigraphy using simultaneous dual channel acquisition, subtraction and ratio images localizes adenomas of the parathyroid with high sensitivity. 2) Selection of patients is important, since the success of this method depends on the weight of the adenoma and the specificity is low. 3) False-positive findings are caused by thyroidal abnormalities and by statistical or electronical artefacts. 4) Ultrasound localizes only large adenomas.

Depts of Nuclear Medicine, Internal Medicine and Pediatrics, University Hospital, Groningen, The Netherlands.

Department of Radiology, Streekziekenhuis Almelo, Postbus 5011, 7600 GA ALMELO, Netherlands.

A5

II. Joint Meeting of the Dutch Society of Nuclear Medicine and the Section for Nuclear and Radiation Chemistry of the Royal Dutch Chemical Society March 14, 1986, Amersfoort, The Netherlands Chairmen: G. Samson and P. van Urk Eur J Nucl Med (1987) 13:A5-A7

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METABOLIC IMAGING: PE~ OR NMR A.M.J. Paans, W. Vaalburg~ Woldring.

PRODUCTION OF 150 L A B E L L E D 02, COR AND CO; A P P L I C A T I O N OF ISO-C02 FOR THE STUDY OF LEFT VENTRICULAR FUNCTION A.G.M. Janssen, J.J.M. de Goeij

PRODUCTION OF IODINE-123 V I A PROTON IRRADIATION OF 99.8% ENRICHED XENON-124 A.J. Witsenboer, R. van der Spek, R.M.W.J. van den Burg, J.J.M. de Goeij

We determined the optimal o p e r a t l o n conditions for a gas t a r g e t set-up for p r o d u c t i o n of 150-1abelled 02, CO2 and Co using the l%N(d,n) l~o reaction /i/ The y i e l d was measured as a function of the gas target thickness and b e a m current. At 4.5 M e V entrance energy the maximum y i e l d amounts to 8.13 mCi. UA-l.s -I . The y l e l d of the recoil labelling reactions as a function of o 2 or C02 concentration in the target gas was m e a s u r e d u s i n g radio gaschromatography. At 02 concentrations above i%, the i~o-o 2 yield (ca 99%) did not improve; the NOx production, however, increased strongly. Applying conventional chemical conversions /i/, the set-up built produces each of the iSo labelled gases with a radiochemical p u r i t y h i g h e r than 99%. The a p p l i c a t i o n of 150-CO2, a d m i n i s t e r e d via inhalation has b e e n reported for the diagnosis of Left v e n t r i c u l a r function. A p r o b l e m is the p a t h of the b a s e line to be subtracted from the timesignal curve (e.g. /2/). For the c o n s t r u c t i o n of the base-line, a four c o m p a r t m e n t model was tested, involving two compartments in the p u l m o n a r y circ u l a t i o n and two others in the left v e n t r i c l e and systemic circulation respectively. For the p r o cessing of the time-signal curves r e c o r d e d a computer p r o g r a m was d e v e l o p e d b a s e d on M a r q u a r d t analysis. F r o m the m e a s u r e d diastolic maxima and systollc m i n i m a values are derived for the relative volumes of the compartments and corresponding detector efficiencies, and an estimate of the LVEF. Results o b t a i n e d w i t h a v o l u n t e e s showed p h y s i o logically realistic values.

We produce sizeable quantities of 1-123 of h i g h p u r i t y via p r o t o n irradiation of h i g h l y enriched xe-124. The reactions leading to 1-123 are: Xe-124(p,2n)Cs-123 ÷ Xe-123 ~ 1-123 and Xe-124(p,pn) Xe-123 ~ 1-123 /1,2/ Since 99.8% enriched Xe-124 is expensive (US $ 150,000 per litre STP) an effective gas target and a reliable gas h a n d l i n g system h a v e b e e n develloped. Since June 1904 this technology is being applied and further improved. The 50 ml conical target chamber is filled w i t h 120 ml STP 99.8% enriched Xe-124. For the h a n d l i n g of the gas a c o m p u t e r - c o n t r o l l e d system has b e e n built, including an emergency recovery system in case of foil disrupture. The xenon is irradiated w i t h a 30 ~A b e a m of 27 MeV protons for 9 hours. After b o n b a r d m e n t , the xenon is p u m p e d cryogenicaly to a temporary storage vessel and the 1-123 absorbed on the wall of the target chamber is recovered by rinsing . The Ee-123 is allowed to decay to 1-123 for 6.6 h, after w h i c h the xenon is recovered to another vessel, and the I 123 is collected, also by rinsing. Both rinsings are p a s s e d through an anion exchanger to remove To-121 and to concentrate the 1-123. The total y i e l d of 1-123 is about 6 mCi/pAh at point of m a x i m u m activity (EOB + l h). The radionuclidic impurity at c a l i b r a t i o n time is less than 0.01%. Since December 1984 pure 1-123 is p r o d u c e d twice a week in batches of 1.2 Ci. The 1-123 is supplied to h o s p i t a l s as NaI, I-hippurate, ~ - I - h e p tadecanoic acid, m e t a - i o d o b e n z y l g u a n i d i n e and Nisopropyi-iodoamphet~nine.

M.G.

With P o s i t r o n E m i s s i o n Tomography (PET) in c o m b i n a t i o n w i t h compounds l a b e l e d ~ith short-lived positron emittlng r a d i o n u c l i d e s l i k e C--11, N-13, 0--15 and F-10 i t is possible to study r e g i o n a l metabolism i n vivo q u a n t i t a t i v e l y , in non invasive ~ay. Not always the carrler-free p r o d u c t i o n of positron emitting radionuclides is achievable, though a very h i g h s p e c i f i c a c t i v i t y o f the end product is possible if precautions are taken. Even for complex syntheses specific activities i n the range o f 1000-10000 Ci/mmol have been r e p o r t e d . With a dose of I0 mCi t h i s l e a d s t o t h e a d m i n i s t r a t i o n o f 10 n m o I . This is sufficient for a PET s t u d y without disturbance of the normal physioloqial levels. NMR i s n o t l i m i t e d to protons but can also be used for other nuclei with a non-zero spin like c a r b o n - 1 3 and phosphorus-31. I f t h e NMR t e c h n i q u e i n combination with carbon-13 is able to provide regional quantitative information on the fate of metabolic compounds in the human b~dy it' w i l l b e on a p a r w i t h PET. To have i n s i g h t in the potentials in m e t a b a l i c i m a g i n g o f PET and NMR i t i s necessary t o compare t h e s e n s i t i v i t y of both techniques. It can b e c o n c l u d e d t h a t t h e i m a g i n g o f m e t a b o l i c compounds using carbon-13 w i t h NMR w i l l n o t be possible without disturbance of the normal metabolic and physiological levels while in the case of the PET technique, images can be obtained without influenclng the physiological level~. Department of Nuclear Medlcine~ University Hospital, O o s t e r s i n g e l 59~ 9713 E Z G r o n i n g e n .

E i n d h o v e n U n i v e r s i t y of Technology, D e p a r t m e n t of Physics, PO BOX 513, 5600 MB Eindhoven, The Netherlands /i/ M . C h e v i g n e et al., R a d l o a k t i v e Isotopen in Klinik u n d Porschung, 15.Bandrl.Teii. G a s t e i n e r Internationales S y m p o s i ~ 1982. V e r l a g H.Egermann. pp.31-36. /2/ J.C.Clark, B.D.Buckingham, S h o r t - l i v e d Radioactive Gases for Clinical Use. B u t t e r w o r t h & Co (publishers) Ltd. 1975.

E i n d h o v e n U n i v e r s i t y of Technology, Department of Physics, PO BOX 513, 5600 MB Eindhoven, The Netherlands /i/ Van den Bosch, R.L.P., Thesis, Eindhoven Univ e r s i t y of Technology, The Netherlands, Prep o s i t i o n 8 (1979). /2/ Grabmayr, P., Nowotny, R., Int. J. Appl. Rad_ lsot., 29, 261 (1978).

A6 24

23 THE PRODUCTION OF RADIONUCLIDES

AT THE CENTER

OF RADIOISOTOPE RESEARCN AT THE VRIJE UNIVER-

SYNTHESIS AND APPLICATION OF 18F-LABELLED COMPOUNDS J.D.M. Herseheid, O.W.M. Visser and A. Hoekstra

SITEIT, AMSTERDAM. R.D. Vis, J.D.M. Rerseheid,

A, Hoekstra,

W.den

~£!!_~_nd__%__~_d_J=_R__~t_hm_~!~_E .................... The Philips AVF cyclotron of the Vrije Universiteit is partly used for the production of radioisotopes.

The energy range of the machine

as well as extensive target facilities make the accelerator preeminently

suitahle for pro-

duction of the isotopes in common use in nuclear medicine.

At present an external beam-

line is available with three extensions ding two gastargets

inclu-

separated from the vacuum-

system with Havar foils and an universal diation facility for the bombardment sorts of solid material.

irra-

of all

It is planned to ex-

tend the cyclotron with an internal target in order to enlarge the production scale at the one hand and save irradiation time at the other.

Up to now produced on a more or less

regular base are the radionuclides: 18F, 57Co,

IIC, 13N,

67Cu,81Rb and 1231,

Center of Radioisotope Research,

C.R.R.

Vrije Universiteit,

1083 A,

Amsterdam,

de Boelelaan

The Netherlands.

Since Positron-Emission-Tomography enables the accurate quantification of radioactivzty in tissue, it offers excellent prospects to study the fate of a certain drug in rive ~sing its radiolabelled analogue. Therefore efficient and fast chemical syntheses have been developed for the preparation of 18F-labelled cytostatics as cancer research tools. Evaluation of their fate in cancer patients will reflect drug kinetics and metabolism of the orginal cytostatics and consequently might be of help in the assessment of the response to cancer treatment on an individual base. Up to now, we have developed an efficient method for the regioselective fluorination of aromatic compounds using arylmercury precursors (J. Chem. ace. Chem. Commun. 19849 655; J. Org. Chem. 1986, in press). Application of this method towards the synthesis of cytostatics containing a phenylmoiety is studied. Since the synthesis of (18F)5-fluorouracll has been completed ( J. Org. Chem. 1986, in press) pharmacological studies are started using 5-FU sensitive and 5-FU resistant tumour models in order to investigate why these type of tumours behave differently towards a 5-FD treatment. In addition, (18F)-5-fluorocytosine has been investigated on tumour-localizing properties (Nucl. Med. Commun. 1985, 455). Using acetylhypoflusrite as a fluorinating agent, a simplified synthesis of 18F- labelled cytoslneand uracil-nucleosides has been developed (Int. J. Appl. gadiat. Isot. 1986, in press . Of these, (18F)-5-fluorocytosine-arabinoside-was found to possess excellent melanoma-localizing properties (gur. J. Nucl. Med. 1986, in press). Studies towards the fluorination of activated quinones as models for mytomycin are currently under investigation. The Netherlands Cancer Foundation is gratefully acknowledged for financial support. Radio-Nuclide Centre (SNC), Free University, P.O. Box 7161, 1007 MC Amsterdam, The Netherlands

25 RADIONUCLIDE PRODUCTIONWITH THE LINEARELECTRON ACCELERATORMEA L. Lindner, P. Polak, J. Visser The Medium-energy Electron Accelerator (MEA) of the National Institute for Nuclear Physics and High-Energy Physics at Amsterdam is since a number of years in operation for carrying out a f u l l scale program on nuclear physics and radiochemistry. The maximum energy attainable is about 50D MeV and w i l l be raised to about 600 MeV in the forseeable future. Such energies in combination with beam intensties up to 100 pA render the f a c i l i t y an interesting tool for the production of a broad spectrum of radionuclides. To this end the energy of the electrons is f i r s t converted to a forward-peaked Bremsstrahlungs photon beam, by passage through a sheet of a suitable high-Z element such as Ta or W. For each combination of electronenergy and target geometry the optimal thickness (several mm) of the converter can be estimated. Out of necessity, the amount of targetmaterial is substantial (tens of grams) and requires adapted techniques for the recovery of the desired radionuclides. At present a beam line for energies ~ 140 MeV is equipped with relatively thin converters and a sweeping magnet to provide a 'clean'-electron-free- photon beam to sustain a program of fundamental radiochemistry - including recoil chemistry with short-lived isotopes such as liC (t½ = 20 min) and laD ( t = 2 min) - as well as projects of an applied nature. Examoles of the ] a t t e r a r e the routine production of ~Cu (t~ = 62 h) for the study of metabolic pathways in milk cows and - in a ~arasitic' setup - of 11C as CO2 for use in plant physiology. Future plans include the installation of an optimized production f a c i l i t y with thick converters making f u l l use of the nominal (~ 600 lleV)energy. This w i l l provide photon fluxes about a factor of f i f t y higher than presently available. The experience to be gained with such a f a c i l i t y w i l l yield the necessary information and experience for a subsequent st~p in which the residual beams of physics experiments - nowadays wasted in beam dumps - are put to use for radionuclide production in a 'parasitic' way. Radiochemistry Department, NIKHEF-K, P.O. Box 4395, 1009 AJ Amsterdam, NL.

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MOTOR FUNCTIONS AND PET STUDIES IN HEMI-PARKINSON PATIENTS. J.P.W.F. Lakke, W. Brouwer, T.W. van Weerden, W. Rutgers, J. Korf~ W.Vaalburg, A.M.J. Peens.

KINETICS OF COPPER ABSORPTIONAND EXCRETIONIN COWS W.T. Binnerts, P. Polak, J. Geradts, R. v.d. V l i s t , and L. Lindner

The u s e of r a d i o t r a c e r s in A b s o r p t i o n , D i st r i but i o n , _Metabo] i s m a n d E x c r e t i o n st udi e s , F.M. Kaspersen, L.P.C. Delbressine, H.G. Hasenack, H. N[euwenhuyse and H.P. Wijnand.

Post mortem s t u d i e s , CSF a n a l y s i s and e f f i c a c y o f L--dope therapy i n d i c a t e d i n 80N o f the cases decreased D A - a c t i v i t y i n Parkinsonism. Post mortem a n a l y s i s o f b r a i n m a t e r i a l f a i l e d t o demonstrate a b n o r m a l t i e s i n DA--receptors. I t has r e c e n t l y become p o s s * b l e t o v i s u a l i z e dopaminergic activity by (F--1S)6-f l u o r o - L - d o p a and dopamine r e c e p t o r s by F--IB--f l u o r o s p i p e r o n e and 11C--methylspiperone d i r e c t l y *n the human b r a i n . We t r i e d t o determine i n hemiparkinson patients possible differences in r e c e p t o r d e n s i t y i n the basal g a n g l i a . We used a t r a c e r dose o f 5 mCi C--11 methyl s p i p e r o n e l a d m i n i s t e r e d by i . v . route in I 0 hemiparkinson p a t i e n t s , both with and without L--doRa medication. P a t i e n t s were i n v e s t i g a t e d with a dual-headed r o t a t i n g p o s i t r o n camera, between 70 and 90 minutes a f t e r the i n j e c t i o n o f the t r a c e r . I n a d d i t i o n the p a t i e n t s were s t u d i e d for left--right differences i n motor behaviour by v i d e o t a p i n g v a r i o u s motor t a s k s , EMG r e c o r d i n g s o f a x i a l r o t a t i o n i n a h o r i z o n t a l p l a i n and t r a c e r t e s t s and t r a c k i n g t e s t s . This allows f o r correlations o f DA--rec~ptor a c t i v i t y and motor abnormalities with the p a t i e n t as i t s o w n c o n t r o l , because o f the u n i l a t e r a l i t y o f the a b n o r m a l i t y . Our data suggest that ParkinsonJsm i s net only the consequence o f DAd e f i c i e n c y , but t a r g e t neurones may be a f f e c t e d as w e l l . Dept. o f Neurology, Nuclear Medicine and B i o l o g i c a l Psychiatry, University H o s p i t a l , 6roningen, The Netherlands.

Previous studies have shown that the main secretory pathway o f copper i s through the stomach walls. The subsequent intestinal discharge and reabsorption are r e l a t i v e l y small and tend to cancel each other, so that faecal analysis gives s u f f i c i e n t information as to the endogenous excretion through the stomach system. The copper absorption was calculated using 64Cu, prepared at ECN, Petten, from pure copper wire in a high flux reactor. The amino acid complex with glycine was injected, or alternatively fed by bailing gun, and the absorption was defined as the quotient of the externally measured l i v e r uptakes a f t e r feeding and i n j e c t i o n . The copper excretion was determined using 67Cu, prepared by irradiation of zinc oxide targets with the MEA f a c i l i t y of NIKHEF-K, Amsterdam, by Bremsstrahlung from electrons with energies higher than lO0 MeV. Reaction: 68Zn (y, p) 6"Cu. In preparat i o n of the pure isotope i t is separated from the large mass of zinc oxide by absorption on a Chelex 100 column. From one week after injection onwards the specific a c t i v i t y of the milk secretion and the endogenous excretion are identical, hence the amount excreted can be obtained by isotope dilution. From our experimental results i t is concluded that copper absorption in modern feed mixtures is very low, causing considerable environmental contamination a f t e r correction with extra copper. Further the endogenous excret i o n , despite large individual v a r i a t i o n , in general approaches the absorbed quantity. Department of Animal Physiology, A g r i c u l t u r a l University, P.O.B. 9101, 6700 AB Wageningen.

The u s e of r a d i o t r a c e r s in t h e s t u d y of t h e f a t e of a d r u g in a n i m a l s a n d m a n is d i s c u s s e d . K i n e t i c p a r a m e t e r s are d e t e r m i n e d w i t h t h e u s e of d r u g s p e c i f i c a s s a y s i n s t e a d of m e a s u r e m e n t s of t o t a l r a d i o a c t i v i t y . A s a r e s u l t of m e t a b o l i s m the l a t t e r m e t h o d w i l l a l w a y s r e s u l t in an o v e r e s t i m a t i o n of t l / 2 - a n d A U O v a l u e s . For t h e e l u c i d a t i o n of m e t a b o l i c p a t h w a y s c o m p o u n d s l a b e l led w i t h radioactive isotopes are essential ; however, one s h o u l d be c e r t a i n t h a t t h e i n t r o d u c t i o n of t h e l a b e l does not r e s u l t in c h a n g e s i n p h a r m a c o l o g i c a l , p h y s i c a l or m e t a b o l i c p r o p e r t i e s of t h e d r u g . For t h e m e a s u r e m e n t of r e t e n t i o n / a c c u m u l a t i o n of a d r u g a n d i t s m e t a b o l i t e s m e a s u r e m e n t of the t o t a l r a d i o a c t i v i t y (for i n s t a n c e by w h o l e body a u t o r a d i o g r a p h y ) is v e r y h e l p f u l ; a l s o i n s i t u a t i o n s w h e r e no m e t a b o l i s m o c c u r s , s u c h as m e a s u r e m e n t s of p r o t e i n - a n d r e c e p t o r - b i n d i n g , t o t a l r a d i o a c t i v i t y m e a s u r e m e n t s c a n be a p p l i e d . Up t i l l n o w o n l y c l a s s i c a l , 3 - - e m i t t i n g r a d i o i s o t o p e s s u c h as 3 H , 1 4 0 a n d 35S h a v e been u s e d ; as a c o n s e q u e n c e o n l y i n v i t r o or e x v i v o m e a s u r e m e n t s a r e p o s s i b l e . T h e a p p l i c a t i o n of s h o r t - l i v e d # + - e m i t t i n g i s o t o p e s s u c h as 1 1 0 or 18F c o u l d offer a w a y to m e a s u r e in v i v o p h a r m a c o k i n e t i c s in t a r g e t o r g a n s or to s t u d y t h e m e c h a n i s m of a c t i o n of a d r u g .

Organon International B.V., p.O.EBox 20, 5340 EBH O S S , The N e t h e r l a n d s

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INDIRECT ESTIMATION OF PLASMA OXALATE USING C14 OXALATE J.A.C. Prenen and H.Y. Oei Determination of renal oxalate (oxal) clearance (clear) and urinary oxal excretion rate permit estimation of plasma oxal indirectly. However, the value obtained will depend on the applied clear method. In this study we compared the results of constant infusion (CI) and single injection (SI) method performed in 6 healthy volunteers. After a priming dose of 2 BCi of C-14 oxal, blood samples were drawn at 7 min intervals during 120 min. Then a second priming dose of i pCi followed by a CI containing 2 ~Ci of C-I~ oxal during 6 hr was given. Blood samples were drawn at 30 min intervals and urine collections were made at 60 min intervals. The SI clear was calculated according to one-compartment (eomp) model and two-eomp model. In the CIstudy equilibration time was 2 hr, clear was calculated according to the standard formula. Both the one-comp and the two-comp model consistently overestimated the renal clear of C-14 oxal as compared with the CI-method: 52% (range: 35-67) and 30% (range: 18-44) resp. In the next study C-L4 oxal clear was determined using CI in 3 groups of subjects: iO healthy volunteers, 12 Datients (Dbs) with normal renal function end g Dts with impaired renal function. (GFR 7-74 ml/min). Comparison of the C-14 oxal clear with the mean endoEeneous creatinine clear determined on the 3 days nreeeding CI revealed a rather constant oxal-to-creatinine clear ratio of 2:1. which appeared to be independent on the degree of renal failure and urinary oxal excretion. We conclude that i. SI overestimates CI oxal clear and 2. Plasma oxal can be estimated from urinary oxal excretion and endogeneous ereatinime clear.

INVESTIGATION OF THE ZINC-STATUS OF PATIENTS WITH RADIO-ZINC C.Cornel isse e and C.J.A.v.d.Hamer ~

MEASUREMENT OF THE TESTICULAR BLOOD FLOW PERCUTANEOUS INJECTED XENON-133 IN THE RAM. J. van Vliet*, H.Y. Oei, A. Hoekstra, A.L. Ruiter-Bootsma, C.J.G. Wensing.

University Hospital, iO1. The N e t h e r l ~ d s

Utrecht,

Catharijnesingel

D e t e r m i n a t i o n of z i n c i n plasma of u r i n e p r o v i d e s seldom a good i n s i g h t i n t h e z i n c - s t a t u s of a p a t i e n t because t h e r e s u l t s a r e too s t r o n g l y i n f l u e n c e d by o t h e r f a c t o r s . T h i s was c o n f i r m e d in o u r s t u d y o f 33 p a t i e n t s and 3 c o n t r o l s . In t h e same s t u d y t o t a l body r e t e n t i o n of i . v . r n j e c t e d 65Zn (D.33 mg Zn c o n t a i n i n g 5)~Ci 6 5 I n ) , measured w i t h a s i m p l e l i n e a r scanner Eurned o u t to be a good parameter f o r d i s t i n g u i s h i n g between normal s u b j e c t s and those who have bec~ne Z n d e f i c i e n t as r e s u l t o f , e . g . , s u r g e r y of t h e d i g e s t i v e t r a c t . However, t h e long o b s e r v a t i o n t i m e (> 150 d) makes t h i s t e s t u n s u i t a b l e f o r clinical use. Measurements d u r i n g t h e f i r s t 10 days p . d . of the total body retention of 65Zn, but also of its plasma-clearance and urinary excretion, although providing information about the loss and shift to other compartments of zinc, did not inform about the zinc status. During this same period, measurements of 65Zn retention in the forearm correlated well with the biol.t½ of the 65Zn as calculated from its total body retention, although the latter required a much longer observation period. Indications are that for measurement of 65Zn rn the forearm an observation period of 3 days may suffice, which would make it feasible to replace the 65Zn (phys.t½=245 d) by 69mZn (phys.t½ =13.9 h). Measurements of 69mZn in the forearm may be a suitable parameter for the zincstatus. 69mZn has also been shown to be the nuclide of choice for the measurement of the plasma-69mZn after an oral dose of 50 mg Zn (containing 1 0 ; C i 69mZn). Such tests have proved their yalue fol7 evaluation of the absorption of Zn from the digestive tract and may possibly also be of value for evaluation of the Zn-status when simulta~ neously the total zinc entering the bJood (vrz., the specific activity of the Zn) is measured. ~St.lgnatius Hospital, Department Medicine, Breda, The Netherlands

of Nuclear

Interunlverstty Reactor Institute, Department of Nuclear Biotechnique, Delft, The Netherlands.

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Na+-fluxes in acid-resistant fish, determined with 24No+ as radiotraeer G.Flik, Z.Kolar, J.A. v,d.Velden, H.Seegers & S.E.Wendelaar Bongo

TC-99m LABELED MONOCLONAL A~TIBODY ANTIFIBRIN FOR IMAGING OF THROMBI IN A RABBIT MODEL J.W. Arndt*, E.K.J. Pauwels*, K.I.J. Feitsma*, W. Nieuwenhuizen**, J.d. Emeis**, and A. germond**

Freshwater fish absorb the major part of ions such as Na + and Ca 2+ needed for growth and homeostasis directly from the water via their gills ( F]ik ~t al. , Am. J. Physiol. 2h9, B432, 1985). Ions are taken up via so-called ionoey%es, mitochondria-rleh cells of the branchial epithelium ~ specialized for the uptake of Na + and Ca 2+ (Flik Gt at., J. exp. Biol. 119, 335, 1985). Water acidification impairs ion uptake, for high proton levels interfere with Cag+-binding to membranes, inhibit transport enzymes and increase branchial permeability to water and cons. Some fish, however, show a remarkable ability to adapt to low pH waters (DE 3 - 4.5). The aim of the present study was to compare the Na balance in two acid-resistant speoies~ viz. the tilapia Oreochromis mossambicus and the mlnnow Umbra py~naea. The latter fish prevails in acidified waters in the Netherlands and Belgium. Both species were well-acclimated and growing at pH 4.5 and 7- The tilapia grows faster at pH 7, the minnow grows faster at pH 4.5. Grovth-related Na+-accumulation was calc~.lated on the basis of weight increase and relationships for body weight (W) and total body Na (Q; Q = 68.3W0.909 and 42.2W 1.03 Bmel Na for the tilapia and the minnow, respectively) and amounted to h - 10 nmol /h Na + for both species. Sodium influx rates were determined by the use of g4Na + produced at the I.R.I. , Delft;influx rates were calculated as the product of the water total Na and the slope of the disappearance curve for tracer from water to fish at t Influx rates are described by Fin(PH 7) = 625 O5-81 and Fin(pH 4.5) = 348W 0"89 nmol/h Na + for the tidapia and Fin(PH 7) = 616W 0.20 and Fin(pH 4.5) = 256W 1.23 nmol/h Na + for the minnow. For a 3.5 g fish the respective values come to 1732 and 1061 nmol/h in tilapia and to 791 and 1195 nmol/h in the minnow, respectively. The ability to enhance Na+-uptake in acidified water may explain the success of the Umbra species under those conditions. Department of Zoology II ~ Toernooiveld 6525 ED NIJMEGEN, the Netherlands.

25,

Detection of thrombi by radionuclide techniques is a continuing problem. Imaging with radiolaheled fibrinogen or plasmine is non-specific. In this investigation we used a monoclenal antibody directed against human fibrin (A2), developed at the gaubius Institute. The antifibrin (AF) is radiolabeled with Tc-99m according to a method developed at our institute (patent applied for). The labeling efficiency, established by means of gelfiltration sn Sephadex Gb0 run in 0.9% NaCI, was always above 95%. In Agarand imunoeleetrophorese and in-vitro thrombus experiments labeled and unlabeled AF had similar properties. Tc-ggm-~F also adhered in vitro to rabbit-thrombi, allowing the possibility to use the rabbit as the experimental model. Artificial thrombi were induced by implantation in the rabbit abdomen of thrombin-soaked cottons. Two to three hours after the implantation TC-99m-AF (1.5 mg, 0.7mgi/mg) was injected i.v. Selntigraphy was performed 45 minutes, 4 and 20 hours after injectlon. Thromhi were visualied with high contast. By way of data-analyses of the seintigrams thrombus-to-soft tissue ratios were calculated. In one experiment ratios of respectively 1.2, 4.9 and 7.7 were found. Thrombi were also induced in the jugular vein without completely obstructing the blood flow. ~Iso, in these cases high contrasted seintigrams were obtalned. The results obtained till now, make it probable that Tc-ggm-AF could he useful for non-invasive localizing and visualizing of thrombi in patients. Div. of Nuclear Medicine, University Hospital Leiden, 2333 AA Leiden. Netherlands, and Gaubius Institute, Berenstraat 5/d, 2313 #LD Leiden, Netherlands.

BY de

The chemo- and radiation therapy applied to patients with Hodgkin's disease is rather successful. A relatively long survival time or even a complete cure is possible. One side effect in such patients is the frequent occurrenee of total destruction of the germinal epitheliLum. Protection of the germinal epithelitun may be achieved by preventing the cytostatic drugs from reaching the testis. We developed a method to interrupt the testieular blood supply temporarily, reversibly and repeatedly. Blockade of flow has been established by an inflatable oceluder placed around the testieular artery at the level of the spennatic cord. A xenon-133 clearance method was used to investigate the effectiveness of the ocoluders. 100 to 300 pCi xenon-133 in about 0.02 ml saline was directly injected in the testis. Gamma emission was measured just above the testis and the testieular flow was calculated. A substantial decrease (gO to 90 %) of testicular blood flow was achieved during inflation of the occluders during 30 or 60 minutes. After deflation a remarkable increase in flow was seen. The disappearance and return of the arterial pulsations after inflation and deflation of the occluders respectively were verified "by Doppler flo~etry. It appeared that the changes in testicuIar blood flow, induced by the occluders, could be estimated satisfactory by the xenon clearance method as well as by Doppler flowmetry. * Department of Anatomy, School of Veterinary Medicine, Yalelaan I, Utrecht, The Netherlands.