Convenient gas phase bromination of [11C]methane and production of [11C]methyl triflate.
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Carbon Radioisotopes↗
Biomedical subjects
M T Vavrek
Publications and source records attributed to M T Vavrek.
A color spot test for the detection of Kryptofix 2.2.2 in [18F]FDG preparations.
A color spot test is described that can confirm the absence of Kryptofix 2.2.2 in 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) in less than 5 min. Pretreated strips of plastic-backed silica gel 60 thin-layer chromatographic medium, saturated with iodoplatinate reagent, are over-spotted with separate droplets of final product [18F]FDG and Kryptofix standard solutions. A blue-black circular spot is clearly visible at Kryptofix concentrations as low as 2 micrograms/mL.
Bridged Bicyclo Compounds, Heterocyclic↗
Back-to-back "one-pot" [18F]FDG syntheses in a single Siemens-CTI chemistry process control unit.
Simple changes in the chemistry, plumbing, and programming of the Siemens-CTI chemistry process control unit (CPCU) effectively double its output by enabling two back-to-back "1-pot" syntheses of 2-[18F]fluoro-2-deoxy-D-glucose in a single unit. Replacement of Kryptofix 2.2.2 with tetramethylammonium carbonate and elimination of diethyl ether from the procedure shorten synthesis time to 48 min, improve process and end-product safety, and increase end-of-synthesis yields from 37% to 52% by minimizing steps and transfer losses.
Animals↗
Solid-phase reversible trap for [11C]carbon dioxide using carbon molecular sieves.
A simple, maintenance-free trapping technique which concentrates and purifies no-carrier-added 11CO2 from gas targets is described. The trap requires no liquid nitrogen cooling and has no moving parts besides solenoid valves. It employs carbon molecular sieves to adsorb 11CO2 selectively from gas targets at room temperature. Nitrogen, O2, CO, NO and moisture in the target gas which could interfere with subsequent radiochemical steps are not retained. Trapping efficiency of 1 g of sieve for 11CO2 from a 240 cm3 target gas dump and helium flush cycle is > 99%, and the adsorbed 11CO2 is recovered quantitatively as a small concentrated bolus from the carbon sieve trap by thermal desorption. This durable trap has performed reliably for more than 1 y with a single charge of carbon sieve. It has simplified the production, and improved the yields of several 11C-radiochemicals at this laboratory.
Carbon Dioxide↗
Ameltolide. II: Placental transfer of radiocarbon following the oral administration of a novel anticonvulsant in rats.
The placental transfer of orally administered ameltolide was evaluated to confirm embryonic exposure in the rat developmental toxicity study (Higdon et al., '91). Dissection techniques were used to determine the amount of total radiocarbon that traversed the placenta and distributed within the embryo in pregnant CD rats 0.75, 2, 5, 12, and 24 h after a single oral gavage dose of 50 mg/kg [14C]ameltolide on gestation day 12. Quantification of radiocarbon within placental and embryonic tissues and amniotic fluid was determined and compared with maternal plasma, liver, kidney, uterus, and ovary. Highest concentrations of radiocarbon occurred at 5 h postdose in all tissues sampled (maternal and embryonic) and then declined steadily over the 24-h time course of the study. Maternal liver contained the highest concentrations of radiocarbon at all time points and peaked at 5.86% of dose at 5 h. Embryonic tissues accounted for less than 0.2% of the administered dose at all time points. Tissue-to-maternal plasma ratios indicated that maternal liver and kidney concentrations were higher than maternal plasma concentrations at all time points. Uterine and ovarian concentrations were approximately equal to maternal plasma concentrations at 5, 12, and 24 h postdose. Although placental, embryonic, and amniotic fluid tissue-to-maternal plasma ratios were less than or equal to 1.0, ratios increased slightly throughout the time course of this study. Results from this study confirm embryonic exposure to radiocarbon associated with [14C]ameltolide and/or its metabolites in the rat developmental toxicity study, which has demonstrated the lack of observable teratogenic effects.
Administration, Oral↗
Separation of hydroxyquinolines by high-performance liquid chromatography.
1. Hydroxyquinolines are important chemicals for pharmaceutical and cosmetic use. This report describes an improved method for separating these chemicals, by utilizing a high-performance liquid chromatography technique. 2. 8-Hydroxyquinoline is an excellent chelating agent. Previous separation procedures failed because of this property. An important requirement for the success of the method described is to provide a metal-free environment for the separation of hydroxyquinolines by replacing metal tubing with Polyplex and polyether-ether ketone (PEEK) tubing and utilizing a metal-free Hamilton PRP-1 column.
Chromatography, High Pressure Liquid↗
Efficient method for the isolation by HPLC, of a major metabolite of the carcinogen 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), the 5-hydroxy derivative.
Previous difficulties in the standard HPLC separation of the 5-hydroxy derivative, a major metabolite of the food mutagen and carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), with the properties of a chelating agent, were resolved by utilizing a nonmetallic tubing and column and a BRP-1 stationary phase. This system separates the already known metabolites by reverse phase mode, but presents the unique advantage of resolving chelating compounds like 5-hydroxy-IQ as a single, clean peak. The procedure may be generally applicable to this class of chemicals.
Animals↗
Identification of sulfate and glucuronic acid conjugates of the 5-hydroxy derivative as major metabolites of 2-amino-3-methylimidazo[4,5-f]quinoline in rats.
New metabolites of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a potent mutagen and carcinogen formed during cooking of meat or fish, have been identified and quantitated in the urine and bile of rats. Administration was either by a pulse gavage dose of 40 mg/kg [2-14C]IQ or by dietary intake of 300 ppm IQ for 6 weeks. The metabolites were isolated by high-performance liquid chromatography and quantitated by radioactivity. They were then characterized by their resistance or sensitivity to hydrolytic enzymes or acid hydrolysis, by nuclear magnetic resonance and mass spectrometry, or coinjection with a synthetic sample. A minor metabolite was the IQ N-glucuronide. A major metabolite was formed by hydroxylation of IQ at the 5-position; it was present in urine and bile and was conjugated as the glucuronide or sulfate ester, which together accounted for about 40% of urinary or biliary metabolites. The unconjugated compound partially adsorbs onto the high-performance liquid chromatographic columns used. The amounts of 5-OH-IQ present as conjugates in urine or bile were similar, irrespective of mode of administration. Thus, hydroxylation of IQ on carbon 5 followed by type II conjugation reactions yields quantitatively important metabolic products.
Animals↗
Metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline in the male rat.
The metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied in the male rat using the radiochemical labels 14C and 3H at positions 2 and 5 of the molecule, respectively. Adult male Fischer 344 rats were administered [2-14C]IQ or [5-3H]IQ by oral gavage at dose levels of 20 or 40 mg/kg body weight. Rats were also given [2-14C]IQ in the diet at a dose level of 300 ppm for 2 days and after administration of unlabelled IQ (300 ppm) in the diet for approximately 6.5 wk for an additional 2 days. In the initial 48 hr following oral administration of 20 or 40 mg [2-14C]IQ/kg body weight, about 40-50% radioactivity was recovered in the urine, and about 30-38% radioactivity was recovered in the faeces. In the initial 72 hr following consumption of [2-14C]IQ (300 ppm) in the diet about 26% radioactivity was recovered in the urine and about 61% radioactivity was recovered in the faeces. Following cannulation of the bile ducts, rats administered a single dose of [2-14C]IQ (40 mg/kg body weight) by oral gavage excreted about 15% of the administered dose in the bile over a period of 2 days. Urine from rats given [2-14C]IQ contained three main polar metabolites that included a glucuronide, a sulphate ester and IQ sulphamate, and a number of less polar metabolites that included IQ, 2-acetylamino-3-methylimidazo[4,5-f]quinoline, 2-aminoimidazo[4,5-f]quinoline and 2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one (7-OH-IQ). Administration of [2-14C]IQ by oral gavage or in the diet gave the same metabolites, but in different amounts. In the faeces of rats given [2-14C] by oral gavage, IQ-sulphamate was the major metabolite in the polar fraction. Non-polar metabolites similar to those found in the urine were also present, but in different amounts. A major, non-polar faecal metabolite, 7-OH-IQ was probably formed as a result of the activity of the intestinal bacterial flora. In rats given a single gavage dose of [2-14C]IQ, excretion of metabolites was higher in the urine and lower in the faeces compared with that in animals fed [2-14C]IQ in the diet. One polar metabolite present in the urine, IQ-sulphamate (39%), was found at considerably higher levels in rats dosed orally with IQ compared with those fed IQ (less than 6%). Thus, IQ is extensively metabolized to give a number of polar and non-polar metabolites, the amounts of which depend, in part, on the mode of dosing.
Affinity Labels↗
Effect of enzyme inducers on the metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the rat.
The effect of enzyme inducers 3-methylcholanthrene (3-MC) and Aroclor 1254 (A-1254) on the metabolic fate of the dietary mutagen and carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in male F344 rats was studied in relation to single dose corn oil and untreated controls. The latter two groups were similar as regards metabolism of IQ. However, the ratio of total metabolites excreted in urine compared with those in feces was higher in A-1254 pretreated rats. In fact, this distinct excretory pattern stemmed from a lower level of IQ-N-sulfamate, and a considerably higher level of 5-OH-IQ sulfate ester, a major metabolite in urine of A-1254-injected rats. Interestingly, 5-OH-IQ glucuronide urinary levels were unaffected by the treatment. Thus, the direct 5-hydroxylation of IQ appears to be considerably increased by 3-MC and more so by A-1254, and under those conditions the resulting 5-OH-IQ is preferentially converted to the sulfate ester, in turn readily excreted in urine.
Animals↗