Steroid assays with radioactive isotopes, with special emphasis on the estimation of urinary aldosterone.
Explore the source record for details and available documents.
Aldosterone↗
SEARCH · PubMed Health
Results for “CARBON AND COMPOUNDS, RADIOACTIVE”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Syntheses of [carbonyl-11C]2-(2-benzoylphenoxy)-N-phenylacetamide from [11C]carbon monoxide by the Suzuki and the Stille reactions.
Syntheses of [carbonyl-11C]2-(2-benzoylphenoxy)-N-phenylacetamide, a radiolabeled inhibitor of human immunodeficiency virus type 1 (HIV 1) reverse transcriptase, were achieved by applying palladium-mediated cross-coupling reactions with insertion of [11C]carbon monoxide. Our interest was focused for the present on a comparison of the Stille and Suzuki methods, using trimethylphenylstannane or phenylboronic acid as alternative coupling reagents, respectively. The Suzuki variant gave a much higher amount of [11C]CO radioactivity trapped in the reaction mixture, but a significant loss of product occurred due to adsorption phenomena on the potassium carbonate present in the heterogeneous reaction mixture. The labeled product was isolated in only 20% yield (based on trapped [11C]CO, not corrected for decay). According to Stille, the reaction provided a product that could be isolated more easily but it did not increase the final yield of the target compound due to a low trapping efficiency for [11C]CO. Both methods were performed in an overall synthesis time of 30min, starting from [11C]CO2, and gave a product with a specific radioactivity of at least 30GBq/micromol. The Stille method as well as the Suzuki reaction allowed the synthesis of a radiochemically pure product in aqueous acetonitrile.
Acetamides↗
[(11)C] Carbon monoxide in selenium-mediated synthesis of (11)C-carbamoyl compounds.
Using either amines, amino alcohols, or alcohols in selenium-mediated synthesis with [(11)C]carbon monoxide, 3 ureas, 6 carbamates, and 1 carbonate were labeled. Tetrabutylammonium fluoride ((TBA)F) was discovered to form a soluble and reactive complex with selenium and drastically increase the radiochemical yields. Of the selected carbamoyl compounds, one was a receptor ligand, one was an enzyme inhibitor, and one was a muscular relaxant pharmaceutical. The (11)C-target compounds were obtained in radiochemical yields ranging from low to almost quantitative and with specific radioactivity up to 1300 GBq/micromol. The radiochemical purity of the final products exceeded 98%. In one case, the corresponding (13)C-substituted compound was produced to verify the position of the (11)C-label. In a typical experiment starting with 16.4 GBq [(11)C]carbon monoxide, 7.0 GBq of LC-purified 5-phenyl-1,3-oxazolidin-[2-(11)C]-2-one was obtained within 20 min from start of the carbonylation reaction (84% decay-corrected radiochemical yield). The presented approach is an interesting alternative to the use of [(11)C]phosgene in labeling chemistry.
Carbamates↗
L-1,2-propanediol exits more rapidly than L-lactaldehyde from Escherichia coli.
Catabolism of the six-carbon compound L-fucose results in formation of dihydroxyacetone phosphate (C-1-to-C-3 fragment) and L-lactaldehyde (C-4-to-C-6 fragment) as intermediates. The fate of lactaldehyde depends on the respiratory growth conditions. Aerobically, lactaldehyde is oxidized to L-lactate by an NAD-linked dehydrogenase (ald product). L-Lactate, in turn, is converted to pyruvate, which enters the general metabolic pool. Anaerobically, lactaldehyde is reduced to L-1,2-propanediol by an NADH-linked oxidoreductase (fucO product). L-1,2-Propanediol is excreted as a terminal fermentation product. In a previous study, we showed that retention of the C-4-to-C-6 fragment of fucose depended on the competition for lactaldehyde by aldehyde dehydrogenase and propanediol oxidoreductase (Y. Zhu and E.C.C. Lin, J. Bacteriol. 169:785-789, 1987). In this study, we compared the wild-type strain and isogenic mutant strains defective in ald, fucO, or both for ability to accumulate radioactivity when incubated with fucose labeled at either the C-1 or the C-6 position. The results showed that although blocking the oxidation of lactaldehyde prevented its assimilation, rapid exit of the 3-carbon unit occurred only when the compound was reduced to propanediol. Moreover, growth experiments on fucose indicated that a double ald fucO mutant accumulated inhibiting concentrations of lactaldehyde. The inner cell membrane therefore appears to be much more permeable to the 3-carbon alcohol than to the 3-carbon aldehyde. The almost instantaneous exit of propanediol appears to be a facilitated process.
Aldehydes↗
Control of the citric acid cycle by glyoxylate. The mechanism of inhibition of oxoglutarate dehydrogenase, isocitrate dehydrogenase and aconitate hydratase.
1. The effects of glyoxylate on partially purified preparations of aconitate hydratase, isocitrate dehydrogenase and oxoglutarate dehydrogenase were compared with those of oxalomalate and hydroxyoxoglutarate (obtained by condensation of glyoxylate with oxaloacetate and pyruvate respectively). 2. Glyoxylate (1mm) did not affect aconitate hydratase and isocitrate dehydrogenase, whereas oxalomalate (1mm) inhibited the enzyme activities completely. 3. Glyoxylate (0.025mm) inhibited oxoglutarate dehydrogenase irreversibly, whereas the same concentrations of oxalomalate and hydroxyoxoglutarate were ineffective. This inhibitory effect was prevented if oxoglutarate, pyruvate or oxaloacetate was mixed with the enzyme before the glyoxylate. 4. Incubation of oxoglutarate dehydrogenase with radioactive glyoxylate produced radioactive carbon dioxide; radioactivity was also recovered in the portion of the enzyme identified with thiamin pyrophosphate. 5. The behaviour of glyoxylate in producing multiple inhibitions of the citric acid cycle, either by direct interaction with oxoglutarate dehydrogenase, or by means of its condensation compounds which inhibit aconitate hydratase and isocitrate dehydrogenase, is discussed.
Animals↗
Labelling and metabolism of methionine-methyl-11 C.
Carbon 11 which is a 20.4 minutes half life isotope emitting positrons was used for methionine labelling on the methyl group by action of 11C-methyl-iodide on DL or L homocysteine. With the method described, 20 to 30 mCi of 11C-methyl-methionine (Specific activity 50 mCi/muM) may be obtained within 25 minutes. The 20 Mev proton beam used for 11C production was 10 muA. The metabolism of 11C methionine studied on mice shows a high uptake in pancreas and to a smaller extent in brain. On humans sequential images were obtained at the head level which allowed measurement of the uptake of the radio-labelled compound in the brain so as to study the radioactivity curve in different parts of the organ.
Adult↗
Vascular clearance of embolic tumor cells and colloidal carbon and the levels of serum lysozyme following muramyl dipeptide administration.
Various doses of coded samples of the parent muramyl dipeptide entity and eight synthetic analogues were injected intravenously into C57BL/6J mice, and the extent of clearance of intravenously injected 5-[125I]iodo-2-deoxyuridine (125I-dUrd) radioactively labeled B16 tumor cells from the lung was measured 3 days later. The results of between one and four experiments with each compound demonstrated that five compounds, including the parent compound, produced dose-dependent increases in the loss of tumor cells from the lung. The same five compounds also caused an increase in the clearance of intravascular carbon clearance. Monitoring of serum lysozyme levels revealed no significant increases compared to controls at doses of up to 1 mg/mouse following muramyl dipeptide (MDP) administration i.v., i.p. or s.c. at any time up to 30 days after administration. Increased pulmonary tumor cell clearance did not occur after s.c. MDP administration and peaked 3 days after i.p. or i.v. MDP, reaching near normal levels by Day 7.
Acetylmuramyl-Alanyl-Isoglutamine↗
Clinical studies of 13C-urea breath test in Japan.
The urea breath test (UBT) using isotope carbon is a non-invasive method for diagnosing H. pylori infection. In Japan, only 13C-UBT using a stable isotope is available, since the clinical use of radioactive isotope 14C-compounds is prohibited. Since there is no worldwide standard protocol for the 13C-UBT, it is therefore important to standardize this test to obtain a cheap, easy, reproducible method. Factors affecting the outcome of 13C-UBT values include sampling times and frequency, the amount of 13C-urea, the cut-off value, the avoidance of oral urease activity, and changes in gastric emptying times and 13C-urea distribution. Mouth rinsing reduces false-positive results due to oral urease activity, particularly within 20 min after ingestion of 13C-urea. A Japanese multicenter trial has shown that the diagnostic utility of 13C-UBT is superb, with the cut-off value 2.5/1000 in 20-min samples after ingestion of 100 mg 13C-urea. The 13C-UBT is a very useful method for diagnosing H. pylori infection.
Breath Tests↗
Degradation of p-nitrophenol by the phototrophic bacterium Rhodobacter capsulatus.
The phototrophic bacterium Rhodobacter capsulatus detoxified p-nitrophenol and 4-nitrocatechol. The bacterium tolerated moderate concentrations of p-nitrophenol (up to 0.5 mM) and degraded it under light at an optimal O2 pressure of 20 kPa. The bacterium did not metabolize the xenobiotic in the dark or under strictly anoxic conditions or high O2 pressure. Bacterial growth with acetate in the presence of p-nitrophenol took place with the simultaneous release of nonstoichiometric amounts of 4-nitrocatechol, which can also be degraded by the bacterium. Crude extracts from R. capsulatus produced 4-nitrocatechol from p-nitrophenol upon the addition of NAD(P)H, although at a very low rate. A constitutive catechol 1, 2-dioxygenase activity yielding cis,cis-muconate was also detected in crude extracts of R. capsulatus. Further degradation of 4-nitrocatechol included both nitrite- and CO2-releasing steps since: (1) a strain of R. capsulatus (B10) unable to assimilate nitrate and nitrite released nitrite into the medium when grown with p-nitrophenol or 4-nitrocatechol, and the nitrite concentration was stoichiometric with the 4-nitrocatechol degraded, and (2) cultures of R. capsulatus growing microaerobically produced low amounts of 14CO2 from radiolabeled p-nitrophenol. The radioactivity was also incorporated into cellular compounds from cells grown with uniformly labeled 14C-p-nitrophenol. From these results we concluded that the xenobiotic is used as a carbon source by R. capsulatus, but that only the strain able to assimilate nitrite (E1F1) can use p-nitrophenol as a nitrogen source.
Aerobiosis↗
A comparison of methods for the separation of [11C]Ro 15-1788 (flumazenil) from its metabolites in the blood of rabbits, baboons and humans.
The determination of the percentage of unchanged [11C]Ro 15-1788 with respect to total radioactivity, essential for the pharmacokinetic exploitation of data of blood radioactivity decrease obtained in PET studies, may be carried out with equal results using either an extraction procedure or a TLC method. The analysis of blood samples of various sources (rabbits, baboons, healthy volunteers and anxious patients) and the use of an automatic linear scanner to quantify the radioactive distribution on the TLC plates lead to the conclusion that only [11C]Ro 15-1788 and its acid metabolite [11C]Ro 15-3890 and no other radioactive compound are present in blood at detectable concentration.
Animals↗
[Attempted identification, by means of radioactive precursors, of a steroid type compound synthetized and excreted by the brown fat of the European hamster (Cricetus cricetus)].
Explore the source record for details and available documents.
Adipose Tissue, Brown↗
Evaluation of carbon-11-labeled KF17837: a potential CNS adenosine A2a receptor ligand.
UNLABELLED: The 11C-labeled KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxa nthine) was evaluated as a PET ligand for mapping adenosine A2a receptors in the central nervous system (CNS). METHODS: The regional brain distribution of [11C]KF17837 and the effect of adenosine antagonists on the distribution were measured in mice by the tissue sampling method. In rats, the regional brain uptake of [11C]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [11C]KF17837 was performed by PET. RESULTS: In mice, a high uptake of [11C]KF17837 was found in the striatum in which A2a receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A2a antagonist CSC but not by nonxanthine-type A2a antagonists ZM 241385 or SCH 58261, or an A1 antagonist KF15372. In the rat brain, [11C]KF17837 was accumulated higher in the striatum than in other brain regions, and the uptake was blocked by co-injection of carrier KF17837. In a monkey PET study, a high striatal uptake of radioactivity was observed. CONCLUSION: Carbon-11-KF17837 binds to adenosine A2a receptors in the striatum. However, the presence of an unknown but specific binding site for xanthine-type compounds also was suggested in the other brain regions. The results also suggested that the in vivo receptor-binding sites of xanthine-type ligands are slightly different from those of nonxanthine-type A2a antagonists.
Animals↗
Pharmacokinetics of 14C-etretinate in healthy volunteers and two patients with biliary T-tube drainage.
The pharmacokinetic profile of 14C-etretinate, a retinoid that is effective in the treatment of psoriasis, was studied in six healthy male volunteers and two biliary T-tube patients. Following a 100 mg oral dose of 14C-etretinate (20 microcurie), etretinate and its major blood metabolites (etretin, isoetretin) were measured by HPLC and total carbon-14 was measured in blood, bile, urine, and feces by liquid scintillation counting. Etretinate was extensively metabolized in healthy volunteers and in T-tube patients. During the absorption phase, 75 per cent of the total radioactivity in the blood could be accounted for as etretinate, etretin, and isoetretin whereas these compounds accounted for only approximately 12 per cent of the blood radioactivity in T-tube patients over the same time period. The blood concentrations of etretinate, etretin, and isoetretin appeared to be substantially reduced in T-tube patients compared to those in healthy volunteers. A higher proportion of the total drug was excreted in the feces and bile of the T-tube patients (84 per cent) than in the feces of healthy volunteers (62 per cent). The major factor responsible for the observed decrease in etretinate blood concentrations following biliary cannulation appears to be the reduced absorption of etretinate due to the elimination of solubilizing bile salts in the duodenum. Carbon-14 related material was detected in urine and feces for as long as 3 weeks in healthy subjects supporting the previous observation that a long terminal elimination half-life exists for etretinate, even following a single dose of the compound.
Bile↗
Acetylcholinesterase imaging: its use in therapy evaluation and drug design.
Several cholinesterase (ChE) inhibitors have been labeled with carbon-11 for visualizing binding sites on acetylcholinesterase (AChE) by positron emission tomography (PET). Following intravenous injection of 1,2,3,4-tetrahydro-9-[(11)C]methylaminoacridine or [(11)C]donepezil, however, the radioactivity distribution does not reflect the regional distribution of AChE in the brain of animals, probably because these compounds have high non-specific binding and/or other specific binding sites in vivo in the brain. PET studies with [(11)C]physostigmine and [(11)C]CP-126,998 in the brain of healthy subjects have shown a radioactivity distribution corresponding to the regional distribution of AChE activity measured in postmortem human brains. These radiotracers may be useful for measuring the occupancy of binding sites on AChE by AChE inhibitors, and for investigating the cerebral pharmacokinetics of such therapeutic drugs. An alternative approach to map AChE is the use of acetylcholine analogue substrates. We have developed N-methylpiperidinyl esters labeled with carbon-11 for quantitative measurement of AChE activity. Currently, two N-[(11)C]methylpiperidine esters, N-[(11)C]methylipiperidin-4-ylacetate (MP4A) and N-[(11)C]methylpiperidin-4-yl propionate (MP4P or PMP), have been used for clinical studies of Alzheimer's disease and other neurodegenerative diseases. Both [(11)C]MP4A- and [(11)C]MP4P-PET have demonstrated not only the reduction of AChE activity in the cerebral cortex of patients with Alzheimer's disease (AD) but also the inhibitory effects of donepezil and rivastigmine on AChE activity in the brain of AD patients. AChE imaging should prove useful for therapeutic monitoring of the effects of ChE inhibitors, including determination of the appropriate clinical doses of newly developed compounds, and can thus prompt the development of novel drugs targeting AChE.
Acetylcholinesterase↗
The effect of methyl palmoxirate on incorporation of [U-14C]palmitate into rat brain.
We examined the dose response, time course and reversibility of the effect of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-14C]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10 mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to infusion of [U-14C]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg, MEP significantly increased brain organic fraction from 40% in controls to 85%, 30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of incorporated [U-14C]PA from 0.67 to 5.7. The incorporation rate coefficient, k*, was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr (34%). All effects were reversed by 72 hr, consistent with a half-life of approximately 2 days for carnitine palmitoyl transferase I. These results indicate that intravenous MEP may be used with [1-11C]palmitic acid for studying brain lipid metabolism in vivo by positron emission tomography, as it significantly reduces the large unincorporated aqueous fraction that would result in high background radioactivity.
Animals↗
The determination of lactate turnover in vivo with 3H- and 14C-labelled lactate. The significance of sites of tracer administration and sampling.
L-[3-3H,U-14C]Lactate was administered to starved rats either as a bolus or by continuous infusion. Tracer administration was performed two ways: injection into the vena cava and sampling from the aorta (V-A mode), or injection into the aorta and sampling from the vena cava (A-VC mode). The specific-radioactivity curves after infusion or injection differed markedly with the two procedures. However, the specific radioactivities of 14C-labelled glucose derived from [U-14C]lactate were similar in the two modes. The apparent turnover rates of lactate calculated from the 3H specific-radioactivity curves in the V-A mode were about half those obtained from the 3H specific-radioactivity curves in the A-VC mode. The apparent contribution of lactate carbon to glucose carbon calculated from specific-radioactivity curves of the A-VC mode was greater than that obtained from the V-A mode. The apparent recycling of lactate carbon calculated from the specific radioactivities for [U-14C]- and [3-3H]-lactate was greater in the A-VC mode than the V-A mode. [U-14C] Glucose was administered in the two modes, but in contrast with lactate the specific radioactivities were only slightly different. An analysis to account for these observations is presented. It is shown that the two modes represent sampling from different pools of lactate. The significance of sites of tracer administration and sampling for the interpretation of tracer kinetics of compounds present in intracellular and extracellular spaces, and with a high turnover rate, is discussed. We propose that for such compounds, including lactate, alanine and glycerol, the widely used V-A mode leads to a marked underestimate of replacement, mass and carbon recycling, and that the A-VC mode is the preferred method for the assessment of these parameters.
Animals↗
Estimation of upper limits on human radiation absorbed doses from carbon-11-labeled compounds.
Radiation absorbed dose estimates for short-lived PET tracers are commonly based on biodistributions in rodents which (because of more rapid distribution and other species differences) may have limited relevance to humans. The initial purpose of this study was to estimate an intravenously injectable quantity of 11C which could not, on a priori grounds, exceed regulatory limits on radiation absorbed doses for individual organs. Upper limits on organ cumulative activities were estimated by assuming that 11C-labeled compounds are instantaneously distributed in the blood plasma, and then transferred solely and irreversibly to a single organ. The rate-constant (min-1) for each organ was taken to be its fractional cardiac output, since the plasma volume of 3 liters is recirculated each minute. The method was extended by using measured time courses of radioactivity in human arterial plasma available from previous PET studies with several 11C compounds in place of the assumption that the injected radioactivity was initially instantaneously distributed throughout the plasma. Calculations for 11C L-deprenyl, cogentin, cocaine, N-methylspiperone, putrescine and 2-deoxy-D-glucose, assuming transfer limited to a single organ, gave the kidneys rather than the thyroid as critical organ in each case. The upper-limit self-doses were 140, 210, 320, 360, 450 and 750 mrad/mCi, respectively, indicating that 34, 24, 15, 14 and 6.5 mCi, respectively, could be administered in a single PET study. These results suggest a strategy for human studies with 11C-labeled compounds: a preliminary study at the 3.5-mCi level would yield 11C arterial plasma data which could in turn be used to give a refined upper limit on radiation absorbed doses. For many 11C compounds, this strategy would demonstrate that sufficient radioactivity could be injected to give acceptable human PET images and would avoid the death of animals for biodistribution studies.
Animals↗
Fate and disposition of bromocriptine in animals and man. II: Absorption, elimination and metabolism.
The disposition and biotransformation of bromocriptine were investigated in mouse, rat, dog, rhesus monkey and man following administration of the drug substance labelled with either tritium or carbon-14. The enteral absorption of bromocriptine was incomplete and amounted to 30-40% of the dose as estimated directly from the sum of biliary and urinary excretion of radioactive compounds in bile duct cannulated rats and monkeys. The main route of elimination was the bile (80-93% of the absorbed dose). Only 1 to 6% of the radioactive dose was recovered in urine of intact animals and man. Extensive biotransformation of bromocriptine is reflected by very complex metabolite profiles in all tested body fluids and by the almost complete absence of parent drug in urine and bile. Of the numerous drug-derived radioactive components seventeen could be identified. In animals the major urinary metabolites were 2-bromo-lysergic acid (7), its amide (3), and the respective isomers at position 8, metabolites 6 and 1. Bromolysergic acid (7) and bromoisolysergic acid (6) accounted for half of the radioactivity in human urine. In rat and monkey bile up to 40% of the radioactivity was associated with metabolites derived from the oxidation (hydroxylation, ring-opening) of the proline fragment (4, 5, 21-24, 29-31). The hydroxylated compounds were present in the form of conjugates with glucuronic acid. These were subsequently deconjugated in the intestine and recovered in the faeces as the free forms. The presence of the parent drug as a major component in rat plasma following intravenous administration and its absence after oral administration indicated that the elimination of bromocriptine proceeded almost entirely by metabolism in the liver. In vitro studies with isolated rat hepatocytes and 10.000 g supernatant of human liver confirmed the in vivo findings. Based on the structures of the identified metabolites it could be concluded that the biotransformation of bromocriptine in man occurred through the same principal pathways as in all investigated animal species.
Animals↗