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[Nuclear medicine methods for the diagnosis of adrenal tumors].

Adrenal scintigraphy using 131I-6-beta-iodomethyl-19-norcholesterol or 6-methyl-75Se-methyl-19-norcholesterol is a function-dependent imaging method which, in association with high-resolution spatial imaging techniques, plays an essential role in the study of adrenocortical hyperfunction. It can distinguish between bilateral cortical hyperplasia and monolateral adenoma or carcinoma and can lateralise the adenoma. In patients with Cushing syndrome, in addition to allowing a distinction to be made between ACTH-dependent forms and independent forms, adrenocortical scintigraphy is particularly appropriate to identify non-common forms of adenomatous hyperplasia. Adrenocortical scintigraphy, performed during dexamethasone administration, is an accurate mean of differentiating bilateral adrenal hyperplasia from monolateral forms (adenoma or carcinoma) in patients with Conn's syndrome. Owing to the gradual spread of high-resolution spatial imaging techniques, the problem of the diagnostic classification of so-called "incidentalomas" (clinically silent masses discovered by chance) is a subject of considerable interest. Adreno-cortical scintigraphy appears to be able to provide an important contribution to identifying the functional behaviour of these tumours. Since the early 80s meta-iodobenzyl-guanidine (MIBG), marked with 131I or 123I, with a structure similar to norepinephrine and characterized by selective tropism for sympathetic and chromaffin tissue, has been used for the scintigraphic study of adrenal medulla. MIBG scintigraphy has been found to be particularly appropriate for the study of intra- and extra-adrenal, single and multiple, benign and malignant pheochromocytomas. This method has a high overall sensitivity and specificity. Lastly, MIBG scintigraphy is useful in the study of neuroblastoma.

3-Iodobenzylguanidine↗

Single and dual labelling of cytotoxic target cells. Comparison of three radioactive tracers, [35S]methionine, [75Se]selenomethionine, and chromium-51.

[75Se]selenomethionine (75SeM) has been shown to provide several advantages over Na(2)51CrO4 (51Cr) labelling of metabolizing target cells: high labelling efficiency and low spontaneous release of 75SeM-labelled target cells permit improved monitoring of cytotoxicity due to extended effector/target ratios in short- and long-term assays. Unfortunately, 75SeM will soon be difficult to obtain. Therefore we studied the suitability of [35S]methionine (35SM) as a substitute for 75SeM. Furthermore, we explored the potential of dual labelling of suspension target cells applying combinations of 35SM and 51Cr or 75SeM and 51Cr. 35SM is a suitable substitute for 75SeM retaining most of the advantages of 75SeM labelling. Although considerably higher labelling of cells is possible we obtained the most efficient labelling with 100-400 kBq/ml of 35SM or 75SeM resulting in a relatively high uptake (3-15 cpm/cell) and very low spontaneous release (1-2%/h) up to 24 h. This permits short- and long-term cytotoxic assays and the use of low numbers of target cells (1 x 10(3)) providing increased cytotoxic sensitivity with reduced amounts of effector cells. Suitable dual labelling of target cells with 35SM plus 51Cr or 75SeM plus 51Cr documented convincingly identical release kinetics for 35SM and 75SeM but partially discordant ones for 51Cr. Depending on the target cell used dual labelling permits discrimination and monitoring of different cytotoxic or release mechanisms in cellular cytotoxicity.

Chromium Radioisotopes↗

Distribution of radiolabeled human and mouse monoclonal IgM antibodies in murine models.

The distribution and kinetics of six human and one murine monoclonal IgM antibodies (MoAb) were studied in BALB/c mice. Labeling was with 111In, 75Se, and 125I. The monomers and pentamers of certain MoAbs were studied. Human distribution studies were also performed. The serum containing [111In]MoAb was obtained from one of the patients 24 hr after administration and injected into mice which were then killed and assayed for 111In distribution. In general, the [75Se] and [111In]MoAbs had distribution and kinetic patterns that were similar while the 125I-labeled MoAbs dehalogenated after 4 hr. Monomers and pentamers had highly similar distributions suggesting that the distribution of IgMs may be based on factors other than molecular size. The murine IgM showed a somewhat different distribution in mice than did human IgMs. Serum from the patient containing [111In]MoAb had a distribution in mice similar to that of the patient with high liver and gastrointestinal uptake. The human imaging indicates that it is possible to target tumor with human IgM MoAbs, but significant problems remain in regard to their clinical use.

Animals↗

Kinetics for the synthetic bile acid 75selenohomocholic acid-taurine in humans: comparison with [14C]taurocholate.

The "apparent" fractional turnover rate of the gamma-labeled bile acid analogue 75selenohomocholic acid-taurine (75SeHCAT) was assessed from decline in radioactivity over the gallbladder area on 4 successive days using a gamma-camera, and was compared in the same subjects with the fractional turnover rate of the corresponding natural bile acid, cholic acid-taurine, labeled with 14C ([14C]CAT) using the classical Lindstedt technique. Very similar results were obtained in 5 healthy individuals (coefficient of variation 4.8%, medians 0.35 and 0.34, respectively). By contrast, the fractional deconjugation rate assessed from zonal scanning of glycine- and taurine-conjugated bile acids on thin-layer chromatography was much less for 75SeHCAT than for [14C]CAT (0.02 and 0.13, respectively; p less than 0.05). The fractional rate for deconjugation plus dehydroxylation was also determined by zonal scanning, and gave lower values for 75SeHCAT than for [14C]CAT (0.02 and 0.12, respectively; p less than 0.05). There was a striking similarity between the fractional rate for deconjugation alone and that for deconjugation plus dehydroxylation for both bile acids in individual samples (r = 0.999, p less than 0.001), suggesting that these two processes might occur simultaneously and probably involve the same bacteria. We conclude that our scintiscanning technique provides an accurate, noninvasive method of measuring fractional turnover rate of a bile acid in humans, and that the finding that 75SeHCAT remains conjugated with taurine during enterohepatic recycling means that absorption should be specific for the ileal active transport site, thus rendering it an ideal substance for assessing ileal function.

Abdomen↗

Uptake and loss of dissolved 109Cd and 75Se in estuarine macroinvertebrates.

Semaphore crabs (Heloecius cordiformis), soldier crabs (Mictyris platycheles), ghost shrimps (Trypaea australiensis), pygmy mussels (Xenostrobus securis), and polychaetes (Eunice sp.), key benthic prey items of predatory fish commonly found in estuaries throughout southeastern Australia, were exposed to dissolved (109)Cd and (75)Se for 385 h at 30 k Bq/l (uptake phase), followed by exposure to radionuclide-free water for 189 h (loss phase). The whole body uptake rates of (75)Se by pygmy mussels, semaphore crabs and soldier crabs were 1.9, 2.4 and 4.1 times higher than (109)Cd, respectively. There were no significant (P>0.05) differences between the uptake rates of (75)Se and (109)Cd for ghost shrimps and polychaetes. The uptake rates of (109)Cd and (75)Se were highest in pygmy mussels; about six times higher than in soldier crabs for (109)Cd and in polychaetes for (75)Se - the organisms with the lowest uptake rates. The loss rates of (109)Cd and (75)Se were highest in semaphore crabs; about four times higher than in polychaetes for (109)Cd and nine times higher than in ghost shrimps for (75)Se - the organisms with the lowest loss rates. The loss of (109)Cd and (75)Se in all organisms was best described by a two (i.e. short and a longer-lived) compartment model. In the short-lived, or rapidly exchanging, compartment, the biological half-lives of (75)Se (16-39 h) were about three times greater than those of (109)Cd (5-12h). In contrast, the biological half-lives of (109)Cd in the longer-lived, or slowly exchanging compartment(s), were typically greater (1370-5950 h) than those of (75)Se (161-1500 h). Semaphore crabs had the shortest biological half-lives of both radionuclides in the long-lived compartment, whereas polychaetes had the greatest biological half-life for (109)Cd (5950 h), and ghost shrimps had the greatest biological half-life for (75)Se (1500 h). This study provides the first reported data for the biological half-lives of Se in estuarine decapod crustaceans. Moreover, it emphasises the importance of determining metal(loid) accumulation and loss kinetics in keystone prey items, which consequently influences their trophic transfer potential to higher-order predators.

Animals↗

Endocrinological applications in nuclear medicine.

Diagnosis and treatment of thyroid diseases have played a major role in Central European Nuclear Medicine. Since 1950, endocrinological nuclear medicine has been one of the strengths of this medical discipline. Not only diagnosis but also conservative treatment with thyroid depressants or hormones is performed by the nuclear medicine specialists. Nuclear medicine also takes part in the diagnosis of other endocrine diseases. The respective procedures include imaging of the adrenal gland (cortex and medulla) as well as of the parathyroid glands. Especially in the latter diseases, imaging was improved through Tc-99m sestamibi scintigraphy. Beyond that, the measurement of bone mineral content contributes to the full spectrum of endocrinological nuclear medicine. The development of In-111 octreotide now plays a limited role in the diagnosis of diseases of the pituitary gland.

3-Iodobenzylguanidine↗

Incidentally discovered adrenal masses: a functional and morphological study.

In the last two years we have examined 17 consecutive patients (11 females and 6 males, 20-66 years old) in whom an unsuspected adrenal mass was discovered by ultrasonography or computed tomography performed for unrelated reasons. Pathological diagnosis was available in 11 cases based on surgical excision in 9 (2 pheochromocytomas of 5 and 12 cm in diameter; 2 ganglioneuromas of 5 and 6 cm; and 5 benign cortical adenomas between 3 and 5 cm), autopsy in 1 (a disseminated malignant pheochromocytoma of 16 cm) and fine-needle biopsy in 1 (a pseudo-adrenal mass of 6 cm, that was a regenerative hepatic nodule). The remaining 6 non histologically diagnosed masses were less than 3 cm in diameter. Endocrine studies showed elevated urinary excretion of catecholamines, vanillylmandelic acid and metanephrines in the pheochromocytomas and borderline high values in ganglioneuromas. A low plasma renin activity was encountered in 2 operated cortical adenomas and 3 non operated incidentalomas. In 2 of the latters aldosterone serum levels were elevated and the final diagnoses respectively were Conn's adenoma and dexamethasone-suppressible hyperaldosteronism with bilateral nodular hyperplasia. An inappropriate cortisol secretion was documented in a cortical adenoma removed. Radio-cholesterol scintiscan showed unilateral or increased uptake on the side of adrenal mass (concordant uptake) in the 5 benign cortical adenomas removed and in 4 non operated incidentalomas. A decreased uptake on the side of the adrenal mass (discordant uptake) was found in the 2 ganglioneuromas while an indeterminate bilateral uptake was found in the 2 remaining non operated incidentalomas and in the pseudo-adrenal mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

In vivo transport kinetics and distribution of taurocholate by rat ileum and jejunum.

The transport kinetics and distribution of taurocholate (TC) from the ileum and jejunum were evaluated in anesthetized Sprague-Dawley rats. Uptake and transport kinetics were determined after simultaneous administration of equimolar solutions of [3H]taurocholic acid ([3H]TC) in the ileum and [24-14C]taurocholic acid ([14C]TC) in the jejunum of anesthetized rats. At TC concentrations between 0.3 and 15 mM, total ileal absorption exceeded jejunal absorption 15- to 25-fold. The apparent Km and Vmax for ileal absorption of TC were 5.6 mM and 65.5 nmol.min-1.cm-1, respectively. Tissue distribution studies following uptake from the ileum and jejunum were done with 75Se-labeled homocholic acid taurine (75Se-HCAT). In the ileum, 82% of the 75Se-HCAT removed from the lumen was found in the bile, 10.6% was found in the ileal wall, and 7.3% was found in the liver. In the jejunum, 24.1% was found in bile, 0.6% was found in the liver, and 75.3% remained in the jejunal wall. These data show that the ileum is much more efficient and better equipped than the jejunum to take up and transport TC at concentrations up to 15 mM.

Animals↗

Dietary assimilation and elimination of Cd, Se, and Zn by Daphnia magna at different metal concentrations.

This study examines the influences of Cd, Se, and Zn concentrations in ambient water on the assimilation, elimination, and release budget of metals, and the clearance rate of Daphnia magna through ingestion of phytoplankton diets. With increasing ambient metal concentration over two to three orders of magnitude, the assimilation efficiencies (AEs) of Cd and Se from two green algal species, Scenedesmus obliquus and Chlamydomonas reinhardtii, decreased significantly. In contrast, the Zn AE from ingested food, which typically was low (<7%), was not impacted by the difference in Zn or Cd concentrations in ingested cells. The Cd AE also was reduced significantly by a high Zn concentration in ingested algae, perhaps due to the competitive assimilation between the two metals. Metal elimination was determined after the daphnids were exposed to the radiolabeled diets for 3 d. The elimination rate constant was not dependent on the metal concentration in ingested food. Similarly, the routes of metal elimination (excretion, egestion, molting, and neonate production) were less influenced by the metal concentration. The rapid elimination of Se and Zn may be attributed to the transfer of these metals from mother to offspring. Except at the highest Cd (917 nM) and Se (1,333 nM) concentrations, there was no significant effect of metal concentration on the clearance rate of the animals. Consequently, the metal assimilation in D. magna may play an important role in the regulation of Cd and Se influx into the animals, whereas the regulation of the metal tissue burden in the animals is unlikely to be achieved through the metal elimination. The trophic transfer factors (TTF) of Cd and Se were related inversely to the metal concentration in the water, whereas the TTF of Zn was less variable at different Zn concentrations. The change of TTF with metal concentration will have important implication for ecotoxicity testing using D. magna, especially when the dietary exposure is incorporated.

Animals↗

Biologic stability of tauro-23-[75Se] selena-25-homocholic acid.

The stability of tauro-23-[75Se]selena-25-homocholic acid (SeHCAT) towards deconjugation by the enzyme cholylglycine hydrolase was compared with that of taurocholate: whereas taurocholate underwent 58% deconjugation within 2 hr, SeHCAT suffered only 8% deconjugation plus 5% conversion to an unknown product within 24 hr. Incubation of SeHCAT under anaerobic conditions for 48 hr at 37 degrees C with human fecal organisms resulted in considerable deconjugation, 7 alpha-dehydroxylation, and dehydrogenation. Twenty-four hours after the simultaneous administration of SeHCAT and tauro-[24-14C]cholate to a rabbit the recovery of 75Se in bile was 90% of that of 14C. Forty-eight hours following administration of SeHCAT to a second rabbit residual bile radioactivity revealed 80% deconjugation and dehydroxylation and 60% reconjugation with glycine. Although SeHCAT is more resistant than taurocholate towards modification by fecal bacterial enzymes, within the rabbit it follows the principal metabolic pathways of the natural bile acids.

Amidohydrolases↗

Comparison of the biodistribution of 75Se- and 131I-labelled monoclonal antibodies in nude mice.

A monoclonal antibody, C-215, against colon cancer, was internally labelled with [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [131I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [75Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue.

Animals↗

Inter-population differences in Cd, Cr, Se, and Zn accumulation by the green mussel Perna viridis acclimated at different salinities.

Trace metal (Cd, Cr, Se, and Zn) uptake from the dissolved phase, assimilation efficiency from the dietary phase, and metal body burden, as well as the clearance rate, apparent water permeability and gill surface area were measured in the green mussel Perna viridis collected from two contrasting salinity sites in Hong Kong coastal waters with following acclimation in the laboratory at different salinities. The concentrations of metals were 1.2-6.4x greater in mussels collected from the low salinity site, i.e. Tai O, as compared with Tap Mun (high salinity) mussels. Influx of Cd and Zn from the dissolved phase increased with decreased salinity. Furthermore, Cr(VI) and Se (selenite) influx were also affected by decreased salinity, in particular below 17 psu, suggesting that speciation was not the only factor to effect metal uptake. Long-term acclimation to different salinity also had an effect on metal uptake. Mussels collected from Tap Mun (high salinity) accumulated metals 1.2-2.2x faster than mussels from Tai O (low salinity) at intermediate and high experimental salinities >17 psu. Metal assimilation efficiencies were unaffected by salinity variation, but gut passage times were significantly longer at low (10 psu) salinities, indicating some effect of lowered salinity on mussels gut physiology. Gill surface area, which was similar in both populations of mussels, and filtration rate, which was generally similar or higher in those groups with low metal uptake, could not explain the inter-population difference in metal accumulation. Although there was no significant difference, due to high inter-individual variability, the apparent water permeability of the Tap Mun population was on average about 1.6x greater compared with Tai O mussels, and may partially account for the difference in metal uptake between these two populations acclimated at salinity >17 psu. Thus, the effect of salinity on metal uptake is dependent on metal biogeochemistry as well as a range of physiological responses. There was a clear effect of acclimation to lowered salinity on metal uptake, which may have important implications for metal accumulation modelling, biomonitoring, and toxicity studies.

Animals↗

Experience with a gastrointestinal marker (51CrCl3) in a combined study of ileal function using 75SeHCAT and 58CoB12 measured by whole body counting.

Introduction of a radioactive gastrointestinal marker (51CrCl3) into a combined study (75SeHCAT + 58CoB12) of ileal function by whole body counting has been undertaken. The technique was assessed in 23 subjects (15 patients with inflammatory bowel disease, six on non-steroidal anti-inflammatory drugs for rheumatoid arthritis, and two normal subjects). Mean (SD) 51CrCl3 retention was only 4.1 (6.0)% on day 4, and was similar on day 7 in subjects given a second dose of 51CrCl3 on day 4. Only one subject had more than 20% of 51CrCl3 retention after four days. A 51CrCl3 correction method adequately corrected for colonic hold up of 58CoB12, when compared with final equilibrium values of 58CoB12 retention. Use of the non-absorbed 58CoB12 fraction as a gastrointestinal marker gave good agreement with the 51CrCl3 method in correcting 75SeHCAT values. In all subjects studied, corrections for colonic retention of 75SeHCAT on day 4, were small (less than 7% of dose) and did not affect the assessment of any subject. In conclusion, an additional gastrointestinal marker such as 51CrCl3 is unnecessary in our combined study since that role can be effected, when indicated by the non-absorbed 58CoB12 fraction.

Adolescent↗