Evaluation of 111In labelled white blood cells by in vitro functional tests and electron microscopy. Comparison of three labelling methods

We have studied the influence of granulocyte labelling with commercially available 111In-oxine, tropolone (trop) or home made 111In-Mercapto pyridine (Merc) prepared by the method of Thakur (1985) on the cell structure by electron microscopy and on the cell function by enzymatic tests, random migration, chemotaxis, phagocytosis and bactericidal activity. The granulocytes were labelled with 400 microCi 111In-oxine in saline or 111In-trop or Merc in plasma. The effect of the chelating agents with and without addition of the tracer was studied (n = 4) with varying concentrations: 5-10 micrograms/ml oxine, 10-160 micrograms/ml trop and 1-4 micrograms/ml Merc. Chemotaxis and random migration were not affected by 111In-trop and clearly suppressed by 111In-oxine and Merc; the other tests were normal. The cell structure was disturbed by Merc. The labelling efficiency was excellent with oxine (90%), acceptable with trop (30%-80%) and poor with Merc (10%-25%). Without 111In, chemotaxis and random migration were normal up to a concentration of 80 micrograms/ml trop, 8.5 micrograms/ml oxine and 1 microgram/ml Merc. With addition of 111In, chemotaxis and random migration were unaffected up to 80 micrograms/ml by trop and markedly suppressed by Merc and oxine. It is concluded that labelling with 111In-trop assures intact cells.     

In-111 Pseudomonas aeruginosa: A simple method of labeling live bacteria with a gamma-emitting radioisotope

We describe a simple and reliable technique for labeling Pseudomonas aeruginosa with a readily available commercial preparation of indium-111 (¹¹¹In) oxine. Labeling of a heavy bacterial suspension with 500 Ci of commercially prepared ¹¹¹In-oxine resulted in a yield of 0.0004 Ci of cell-associated ¹¹¹In per 10⁶ colony-forming units (CFU). The label was 88% bacterially associated and did not effect viability of the organism. Radiolabeling a gram-negative organism with ¹¹¹In-oxine provides a nontoxic, stable gamma-emitting bacterial tracer.     

Usefulness of a latex agglutination assay for FDP D-dimer to demonstrate the presence of postmortem blood

D-dimer, a specific fragment resulting from degradation of cross-linked fibrin, is an essential marker for the diagnosis of disseminated intravascular coagulation (DIC). Rapid assay for D-dimer using monoclonal antibody coated-latex particles might be useful for discriminating between postmortem and antemortem blood in bloodstains. We tried to detect D-dimer in nine postmortem blood samples by the rapid latex agglutination assay and to quantify them automatically using the latex photometric immunoassay system. The results showed that all samples were positive and that their amounts of D-dimer were 335–2,800 g/ml (the normal blood level, <1 g/ml; the pathogenic blood level with DIC, 1–100 g/ml). Next, nine stains made of postmortem blood were examined by the rapid latex agglutination assay. The result showed that only one case (D-dimer 335 g/ml blood) showed weak positive while the others (D-dimer 600–2,800 g/ml blood) were positive. The present study indicates that the latex agglutination assay for D-dimer can be useful to demonstrate the presence of postmortem blood.     

Radiopharmacokinetics and radiation dose from 99mTc-HM-PAO (Preliminary report)

Whole body retention measurements were performed in volunteers after i.v. injection of ^99mTc-HM-PAO (Ceretec^®). The organ accumulation was measured in mice and data were transferred to standard man according to ICRP. Absorbed dose calculations were made with these data by using the concept of absorbed fractions (MIRD method). In man, the whole body retention and the retention in the brain could be calculated by direct measurement, absorbed doses to the other organs could only be derived from animal data. The absorbed dose to the brain derived from human data (10.3 Gy/MBq) is greater by a factor of 2 than that derived from animal data. The highest absorbed dose was received by the thyroid (24.4 Gy/MBq), the absorbed dose to the ovaries, testes and whole body ranged from 2.8 to 4.2 Gy/MBq.Dedicated to Professor Dr. Guenter Liess on the occasion of his 65th anniversary     

Über den natürlichen Thalliumgehalt des menschlichen Körpers

Zusammenfassung Es wird eine neue spektrographische Methode zur Bestimmung von Thallium in biologischem Material beschrieben. Dieses Verfahren besitzt eine große Empfindlichkeit, da durch die Extraktion mit einem Komplexbildner (DADDTC) eine starke Anreicherung erfolgt. Es werden auch physiologische Thalliummengen erfaßt; diese liegen zwischen 0,1–0,6p/kp (Tabelle 1 und 2); es sind auch Werte von 1,0–3,0p/kp gefunden worden.Bei der Untersuchung exhumierter Leichen ist es sehr wichtig, nicht nur das biologische Material, sondern auch die in unmittelbarer Nähe der Leiche befindliche Kleiderreste auf dieses Element zu untersuchen, da Konzentrationsverschiebungen durch die Verwesungsflüssigkeit möglich sind.Bei der Untersuchung einer exhumierten Leiche (eines mit Thallium vergifteten Mannes) konnten in der Kleidung Thalliumkonzentrationen von 16–60 p/kp festgestellt werden, während das biologische Material einen Gehalt von 0,9–4,0 p/kp aufwies (Tabelle 4). Leerproben mit exhumierten Leichen ergaben, beim Vorliegen von nur physiologischen Thalliummengen, keine Anreicherung an der Kleidung.

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Summary A new spectrografical method to determine thallium in biological material is described. This procedure produce great sensivity, as by extraction of the element in complex with DADDTC follows a great enrichment. Physiological amounts of thallium can be registered too; they run up to values between 0.1 and 0.6 p/kp (Table 1 and 2), there are also found values of 1.0–3.0 p/kp.By research of exhumed corpses in order to find this element it is of great importance to investigate not only biological material, but also the rests of clothes direct nearby the corpse, for shifting of concentration by putrefaction-liquid is possible.Investigating a exhumes body (of a man poisoned with thallium) we found in clothes a thallium concentration of 16–60 p/kp, whereas the biological material showed an amount of 0.9–4.0 p/kp (Table 4).Empty-testa with exhumed corpses possessing physiological amounts of thallium yielded no enrichment in clothes.

     

125I-β-iodo-D-alanine-synthesis,biodistribution and antimicrobial activity

Methyl N-carbobenzoxy--iodo-D-alaninate (1) served as an intermediate to synthesize methyl -iodo-D-alaninate (2) and -iodo-D-alanine (3). The ¹²⁵I-labeled compound 1 was synthesized by the melt method and used to synthesize ¹²⁵I-labeled compounds 2 and 3. Compound 3 was shown to be substrate for D-amino acid oxidase. It was also shown that compounds 2 and 3 were rapidly eliminated from normal mammalian tissues and that compound 3 inhibited the Escherichia coli growth in a dose-dependent manner at 100–500 g/ml while compound 2 showed no effect at 500 g/ml level. Therefore, it was suggested that compound 3 may serve as an abscess localizing agent.Research carried out at Brookhaven National Laboratory under contract with the U.S. Department of Energy (No. DE-AC-02-76CH00016) and supported by its Office of Health and Environmental Research     

Messung des Hämoglobingehalts von frischem Blut durch atomabsorptionsspektralphotometrische Eisenbestimmung

Zusammenfassung Es wird eine atomabsorptionsspektralphotometrische Eisenbestimmung in Vollblut zur Messung des Hb-Gehalts beschrieben. Ihre Anwendung wird für die Hb-Bestimmung von faulen Blutproben empfohlen, da hier die photometrische Cyan-Met-Hb-Methode nicht immer zuverlässig ist. Für den Probenansatz werden zu 5 ml 0,5%iger wäßriger Triton-X-100-Lösung 0,1ml Blut pipettiert; nach erfolgter Hämolyse kann die Probe vermessen werden. Die Eichung des Atomabsorptionsspektralphotometers erfolgt mit einem Standard von 10g Fe/ml H₂O. Proben mit einem Fe-Gehalt von 1g bis 20g/ml H₂O (1,6g–32g Hb/100ml) liegen im linearen Meßbereich des Gerätes. Die atomabsorptionsspektralphotometrische Methode wird mit der photometrischen Messung verglichen; zwischen den Meßergebnissen besteht ein linearer Zusammenhang.     

Pretargeting in tumored mice with radiolabeled morpholino oligomer showing low kidney uptake

We have recently shown that accumulation in mouse kidneys of technetium-99m labeled phosphorodiamidate morpholinos (MORFs) increases with the number of cytosines in the base sequence. To improve tumor/kidney ratios in tumored mice, pretargeting studies were performed with a cytosine-free MORF. An 18-mer MORF (5-TCTTCTACTTCACAACTA) was conjugated to the anti-CEA antibody MN14 (Immunomedics) and administered to nude mice bearing LS174T tumors. Thereafter, the ^99mTc-labeled cytosine-free cMORF (5-TAGTTGTGAAGTAGAAGA-amide-MAG₃) was administered. For comparison, the identical study was repeated but with our original pair of 18-mer MORFs (5-GGGTGTACGTCACAACTA-conjugated MN14 and ^99mTc-labeled 5-TAGTTGTGACGTACACCC-amide-MAG₃). Surface plasmon resonance was used to show that the hybridization affinities of the original and the modified pair of MORFs were essentially equal. Hybridization of the cytosine-free cMORF-^99mTc to MN14-MORF was demonstrated in vitro by size-exclusion high-performance liquid chromatography. At 3 h, kidney levels in normal mice were 2.0%ID/organ for the modified cMORF vs. 4.1%ID/organ for the original cMORF sequence, while at 24 h, these values were 0.9% vs 1.8%ID/organ. Pretargeting studies in tumored mice receiving 25 g of conjugated antibody, 0.5 g of labeled cMORF 48 h later, followed by imaging and sacrifice at 3 h showed that kidney levels were reduced using the cytosine-free cMORF. Moreover, tumor accumulation was about 3.6%ID/g and was independent of sequence. The whole-body images clearly reflected the improved tumor to kidney ratios. By choosing a cytosine-free base sequence for pretargeting studies, kidney accumulation of cMORF-^99mTc was reduced without adversely influencing tumor accumulation. The lowering of kidney radioactivity levels in this way may be important to reduce toxicity to this organ in connection with pretargeting radiotherapy studies.     

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis

The level of the aminoterminal propeptide Col 1–3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6±1.1 g/l; N: 8.6±1.8 g/l), while significantly increased levels were found in PMF (24.8±2.2 g/l).During a follow-up of 1 year, a slight increase of 2 g/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 g/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as -thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide.These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.     

Functional alterations of human platelets following indium-111 labelling using different incubation media and labelling agents

Human platelets were labelled in the absence or presence of plasma using indium-111 labelled oxine sulphate, tropolone or 2-mercaptopyridine-N-oxide (MPO). Under in vitro and in vivo conditions, platelet functions were evaluated by measuring their aggregability, survival, recovery and early distribution. High labelling efficiency was achieved in saline labelling, whereas with plasma labelling, it was necessary to concentrate the platelet-rich plasma to 4.8 × 10⁶ platelets/l. The aggregation of platelets labelled in plasma or saline was compared with that of controls; platelets labelled in saline showed lower aggregability in 2 M ADP but not in 5 M ADP nor with collagen. No significant differences in platelet survival and recovery were noted between platelets labelled in plasma and those labelled in saline. Our results indicate that partial loss of ADP aggregability in vitro does not influence the in vivo viability of platelets labelled in saline. Scintigraphic studies showed that platelets labelled in a saline medium were temporarily sequestrated in the liver but not in the spleen or heart. Thus, platelet labelling in saline does not affect platelet function adversely, but platelets labelled in plasma are more desirable for assessing the early distribution of platelets in the reticuloendothelial system.     

Improvement of brain single photon emission tomography (SPET) using transmission data acquisition in a four-head SPET scanner

Attenuation coefficient maps (-maps) are a useful way to compensate for non-uniform attenuation when performing single photon emission tomography (SPET). A new method was developed to record single photon transmission data and a-map for the brain was produced using a four-head SPET scanner. Transmission data were acquired by a gamma camera opposite to a flood radioactive source attached to one of four gamma cameras in the four-head SPET scanner. Attenuation correction was performed using the iterative expectation maximization algorithm and the-map. Phantom studies demonstrated that this method could reconstruct the distribution of radioactivity more accurately than conventional methods, even for a severely non-uniform-map, and could improve the quality of SPET images. Clinical application to technetium-99m hexamethylpropylene amine oxime (HMPAO) brain SPET also demonstrated the usefulness of this method. Thus, this method appears to be promising for improvement in the image quality and quantitative accuracy of brain SPET.This work was presented in part at the World Congress on Medical Physics and Biomedical Engineering, 7–12 July 1991, Kyoto, Japan     

How to diagnose polysulphide poisoning from tissue samples

Summary We carried out animal experiments to toxicologically verify polysulphide poisoning by analyzing tissue samples. A bathing agent containing calcium polysulphides was administered orally to rats, and then polysulphides and sulphide, the decomposed product of polysulphides, were analyzed by GC and GC/MS. The concentrations of polysulphides (mol/ml or g) were found to be highest in blood (0.196), followed by the liver (0.051), the lungs (0.018) and kindneys (0.013), but were below the detection limit (0.005 mol/g) in the other tissues tested. Sulphide was detected in all the tissue samples and was found to be highest in the blood (0.518 mol/ml), this being 40 times higher than that required for fatal poisoning in the case of hydrogen sulphide. Polysulphide poisoning was considered to be confirmatively diagnosed by detecting and measuring polysuphides and supplementarily sulphide in body tissues, most pertinently in the blood. Two practical cases of suspected poisoning by polysulphides are briefly described.     

Untersuchung des Histamingehalts im Gehirn der Ratte nach experimentellen Verbrennungen

Zusammenfassung An Ratten wurden auf etwa 20% der Körperfläche ausmachenden Arealen der Rückenhaut Verbrennungen III. Grades hervorgerufen und 1, 5, 10 und 30 min. 2, 6, 12 und 24 Std sowie 2, 3, 5 und 7 Tage darauf der Histamingehalt im Gehirn bestimmt.In der Gehirnsubstanz der Kontrolltiere konnten 0,44 g/g freies und 0,78 g/g Gesamthistamin nachgewiesen werden, während in jener derverbrannten Ratten der Gehalt an freiem Histamin in der 1. min um 40,9%, in der 2. Std um 386,4%, in der 24. Std um 179,5%, am 2. Tage um 295,4% und am 5. Tage um 502,3% erhöht war. Der Gesamthistaminwert zeigt einen analogen Anstieg zum freien Histamin und erreicht sein Maximum am 5. Tage mit 629,5%.Innerhalb des untersuchten einwöchigen Intervalls betrug der in der Hirnsubstanz der verbrennungsverletzten Ratten ermittelte Gehalt anfreiem Histamin im Mittel 1,19±0,69 g/g und die Gesamthistaminmenge im Mittel 2,31±1,65 g/g.In der Gehirnsubstanz der postmortal lädierten Ratten blieb der Histamingehalt im Verhältnis zu dem der Kontrolltiere unverändert.

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Examination of the histamine content of the brain in experimental burns injuries in rats

Summary Third-degree burns on 20% of body surface were induced on the back skin of rats. After 1, 5, 10, 30 min; 2, 6, 12, 24 hrs and 2, 3, 5, 7 days the histamine content of the brain was determined by a spectro-fluorometric method.In the brain of control rats 0.44 g/g free histamine and 0.78 g/g total histamine were found. The free histamine level in brains ofburned rats showed in the 1st min a rise of 40.9%x, in the 2nd hr 386.4%, on the 24th hr 179.5%, on the 2nd day 295.4%, on the 5th day 502.3%.In the 1 week interval the average level of thefree-histamine in brains of burned rats was 1.10 + 0.68 g/g, that of total histamine 2.31 + 1.65 g/g. In the brain of postmortal burned rats the histamine showed no change as compared with control rats.

     

In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

Radiolabelled 2-Cabomethoxy-3-(4-iodophenyl)tropane (-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2-Carbomethoxy-3-(4-iodophenyl)nortropane (nor--CIT) is a des-methyl analogue of -CIT, which in vitro has tenfold higher affinity (IC₅₀=0.36 nM) to the serotonin transporter than -CIT (IC₅₀=4.2 nM). Nor--CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor--CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [¹²⁵I]nor--CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [¹¹C]nor--CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [¹¹C]nor--CIT were 20%–40% higher than those previously obtained with [¹¹C]-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor--CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.     

Dosimetry of iodoantipyrine

Dosimetry of iodoantipyrine labeled with radioactive iodine was determined by measuring the biodistribution of ¹³¹I-iodoantipyrine in 41 female rabbits. Following administration of the radiopharmaceutical, subjects were killed at 0.5, 6, 12, 17, 24, 36, and 48 h. Organs and samples of tissues and body fluids were assayed. Results were corrected for physical decay. Exponential functions were employed to describe the time-concentration curves; representative value would be the biological half life of 9.96±0.55 h for blood. Cumulated activity estimates for ¹²³I, ¹²⁵I and ¹³¹I were then computed. Extrapolation to absorbed dose in humans followed the formulation of the Medical International Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. The whole body absorbed doses are 7 Gray, 5 Gray and 29 Gray per MBq of ¹²³I, ¹²⁵I, and ¹³¹I administered respectively.This work was supported by a research grant from the Veterans Administration     

Forensic toxicological analysis of tetrahydrofuran in body materials

Summary Routine analysis of tetrahydrofuran (THF) in biologic materials has become feasible using GC and GC/MS and the headspace method. Problems of the headspace method and this substance which has a high water-and lipid-solubility were overcome by using the salting-out technique.Identification was made by mass spectral examination, in case of concentrations over 5 g per sample. For quantitative determinations, tetrahydropyran (pentamethylene oxide) was used as an internal standard in GC, and a stable isotopic substance, octadeuterated THF (TDF) in GC/SIM. THF was detected in 1 g per sample by GC, and 0.1 g per sample by GC/SIM.THF blood levels in laboratory animals reached their highest values about 1 h after the oral administration, and the half-life was about 5 h. Ratios of tissue levels to blood were ca. 1.5–2 in the adipose tissue and kidney, and fairly equal in the brain, liver, spleen, and muscle.

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Abbreviations GC gas chromatography - MS mass spectrometry - SIM selected ion monitoring - IS internal standard - THF tetrahydrofuran - TDF octadeuterated THF - THP tetrahydropyran Supported by a grant-in-aid (1983) for scientific research from the Ministry of Education of Japan     

A rapid method for detecting barbiturates in serum using EI-SIM

A simple and rapid method for analysis of barbiturates in serum has been developed. In order to extract and clean barbiturates in serum, a separation column packed with Extrelut and Florisil was used, and the eluate was directly analyzed by means of electron impact selected ion monitoring (EI-SIM). Selected ions used were base peak ions of 10 barbituartes, and the internal standard used was allobarbital or secobarbital. The calibration curves were linear over the range 0.5–5 ng. Extraction of replicate serum samples containing 20 g/1.5 ml and 5 g/1.5 ml resulted in a recovery of 87.2–105.2% and 81.6–104.6%, respectively, with the exception of phenobarbital, which was 151.9% and 172.1%, respectively. Secobarbital was also analyzed in the serum of 13 patients who had been given secobarbital intravenously. In 3 out of 10 cases, Secobarbital levels greater than 1 g/ml were detected more than 72 h after administration. This method seems to have possibilities for clinical use.Paper presented at the 2nd International Symposium ADVANCES IN LEGAL MEDICINE, Berlin, Germany, August 30–September 1, 1993     

99mTc-labelling of leucocytes with 99mTc-DPO: a complex developed for myocardial imaging

The lipophilic ^99mTc-DPO complex, developed as a myocardial imaging radiopharmaceutical, was used to label leucocytes. After an incubation of 0.1 ml ^99mTc-DPO (8 g DMPE*2HCl) with mixed leucocytes in plasma, the labelling efficiency was over 70%. During incubation in 5 ml plasma, a loss of activity was found between 20% (1 h) and 35% (3 h) caused by elution. Disturbances of cell viability could not be found with the help of the chemiluminescence test. The in vivo recovery was determined in three dogs and was 45%–50% (0.5 h), 30%–36% (1 h), and 18%–24% (3 h). Autologous ^99mTc-DPO-leucocytes were used on seven patients with suspected osteomyelitis, there were four true negative and three true positive results. The target/nontarget ratio determined by ROI in the positive cases was 1.8 to 2.5 at 3 h after injection.     

Radioimmunoassay of serum thyroglobulin

A radioimmunoassay technique using a double antibody procedure for human serum thyroglobulin (HTg) is described. Only antigen labeling with iodine-125 is performed extemporaneously, the other reagents being purchased commercially. Quality criteria were: sensitivity (2 g/l), interassay reproducibility (coefficient of variance, C.V.=11%) and specificity are comparable with those of previously published techniques. Normal limits for serum HTg concentrations were established on the basis of 65 assays (33.0±21.20 g/l). In 69 subjects exhibiting goiters and cold nodules, the values observed were considerably higher and more dispersed (81±57 g/l); the same observation was made for the cases of Basedow's disease studied. Patients who had undergone thyroid ablation for thyroid cancer exhibited a low or nondemonstrable HTg concentration, except for seven subjects showing osseous and/or pulmonary functionally active metastases of a differentiated cancer whose HTg levels were significantly higher (300–400 g/l). These results concur with several previous reports in emphasizing the interest of assaying serum HTg during the surveillance of differentiated cancers of the thyroid.     

99mTc-Diethyl-iodo-HIDA (JODIDA): A new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients

The new HIDA derivative, ^99mTc-dimethyl-iodine-HIDA (JODIDA), was compared with ^99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 mol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 mol/l (6 and 76 mg/dl), JODIDA showed significant advantages over DISIDA: non-visualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patients, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80–100 mol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage. As there are also no clinical disadvantages, it could become the rediopharmaceutical of choice for hepatobiliary imaging.