Average Radiochemical Yield Research Articles

A remote control process for the routine synthesis of branched chain [1- 11C]α amino acids

We describe the implementation of a modified Bucherer-Strecker synthesis for the facile production of several natural branched-chain, [ 11C]carboxy-labelled amino acids and of a carbocyclic analogue. The amino acids obtained by this process include the following: dl-Val, dl-Leu, dl-Ileu and α-amino-isobutyric and 1-amino-cyclopentane-1-carboxylic acids. A remote control apparatus specifically constructed for the routine, safe application of this process is also described. This apparatus allows the sequential batch-production of two amino acids, either the same of different, in average radiochemical yields between 1.48 and 2.59 GBq (40 and 70 mCi) and with average specific activities of 92.5 GBq (2.5 Ci)/mmol.

PET studies of potential chemotherapeutic agents—X. Synthesis of “no-carrier-added” ( 11C)-HECNU: The hydroxyethyl analog of the chemotherapeutic agent BCNU

Carbon-11-labeled HECNU [1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea] a potential chemotherapeutic agent, has been prepared by the nitrosation of the corresponding carbon-11-labeled urea, HECU, [1-(2-chloroethyl)-3-(2-hydroxyethyl) urea]. The isomeric byproduct of nitrosation, 1-(2-chloroethyl)-3-nitroso-3-(2-hydroxyethyl) urea can be efficiently removed by preparative scale HPLC on a Partisil column. ( 11C)-HECU was prepared by reacting ethanolamine with ( 11C)-2-chloroethyl-isocyanate which was itself prepared by reacting ( 11C)-phosgene with 2-chloroethylamine hydrochloride suspended in dioxane at 60–65°C. This synthesis yielded ( 11C)-HECNU with an average radiochemical purity of 98% in an average radiochemical yield of 18% relative to the radioactivity measured at the end of the 11C-phosgene introduction.

Synthesis and in vivo characterization of d-(+)-(N1-[ 11C]methyl)-2-Br-LSD: a radioligand for positron emission tomographic studies of serotonin 5-HT 2 receptors

d-(+)-Nl-Methyl-2-Br-LSD (MBL), which displays high affinity and selectivity for serotonin receptors in vitro, has been labeled with carbon-11 for localization of cerebral serotonin 5-HT 2 receptors by positron emission tomography. [ 11C]MBL was prepared from [ 11C]iodomethane and d-(+)-2-Br-LSD within 20 min from end of bombardment. The average specific activity of [ 11C]MBL was 2300 mCi/μ mol and the average radiochemical yield was 17%, both at end of synthesis. The in vivo regional distribution of radioactivity in brain after i.v. administration of [ 11C]MBL to mice paralleled the known density of serotonin 5-HT 2 receptors. The maximum specific binding, defined by a frontal cortex to cerebellum radioactivity concentration ratio of 5.4 to 1, was reached 30 min postinjection. Administration of ketanserin, a potent serotonin 5-HT 2 receptor antagonist, markedly blocked radioligand binding in all brain regions examined except cerebellum.

Synthesis of [ 11C]SCH 23390 for dopamine D1 receptor studies

The optimal conditions for the synthesis of 11C-labeled SCH 23390 by radio-methylation of its desmethyl precursor, SCH 24518, with [ 11C]iodomethane are described. Isocratic reversed phase HPLC was used for the purification of [ 11C]SCH 23390. The specific activity range in 30 runs was 10–235 Ci/mmol and average radiochemical yield was 72% based on [ 11C]iodomethane. Mean synthesis time was 40–60 min from the end of bombardment. Preliminary animal studies indicate that [ 11C]SCH 23390 would be useful in visualizing D1 receptors in a living brain by positron tomography.

Radiosynthesis of a selective dopamine D-1 receptor antagonist: R(+)-7-chloro-8-hydroxy-3-[ 11C]methyl-1-phenyl-2,3,4,5-tetrahydro- 1H-3-benzazepine ([ 11C]SCH 23390)

Carbon-11 labeled SCH 23390, a selective dopamine D-1 receptor antagonist (Fig. 1b), was prepared by N-alkylation of the nor-methyl precursor with [ 11C]iodomethane. The product was purified by semi-preparative HPLC and shown to be radiochemically pure at the end of synthesis. The synthesis was completed in approximately 22 min with an average radiochemical yield of 28% (based on [ 11C]iodomethane) and an average specific activity of approximately 1950 mCi/μmol calculated at the end of synthesis.

Measurement of 99Tc in low-level radioactive waste from reactors using 99mTc as a tracer

A radiochemical procedure has been developed for measuring 99Tc in major low-level radioactive waste streams from commercial nuclear power facilities which contain numerous potential contaminants. Separation was by alkaline precipitation and anion exchange chromatography; trace amounts of 60Co and other radioactive contaminants were removed by solvent separation. Pure separations were obtained with average radiochemical yield of 47.3 ± 4.3% determined by a 99mTc tracer. The lower limit of detection for 99Tc was found to be 0.16 pCi/g based on 10-g sample and a 100-min counting time.

An improved synthesis of (3-N-[ 11C]methyl)spiperone

An improved radiochemical synthesis of (3-N-[ 11C]methyl) spiperone is reported. The radiotracer was prepared by N-alkylation of spiperone in dimethylformamide in the presence of equimolar aqueous tetrabutylammonium hydroxide and was purified by semi-preparative reversed phase high performance liquid chromatography (C-18 HPLC). The average radiochemical yield was approximately 21% end-of-synthesis (EOS) with an average specific activity of over 2750 mCiμ mol EOS. The total time for synthesis and specific activity determination was approximately 21 min.

Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: Potential in vivo markers of hypoxic tissue

Three 18F labeled fluoronitroimidazoles have been prepared as potential in vivo markers of hypoxic cells in tumors, and ischemic areas of the heart and brain. 1-(2-Nitroimidazolyl)-3-[ 18F]fluoro-2-hydroxypropanol ( 18F]fluoro-normethoxymisonidazole) 4, 1-(2-[ 18F]fluoroethyl)-2-nitroimidazole 7, and 1-(2-[ 18F]fluoroethyl)-2-methyl-5-nitroimidazole ([ 18F]fluoro-norhydroxymetronidazole) 10 were prepared in average radiochemical yields of <1%, 23% and 15–43% (8% at the no carrier-added level) respectively at end-of-synthesis. The in vivo biodistribution in rats was determined for each of the 18F labeled fluoronitroimidazoles. At 1 and 3 h after administration, the tissue distribution of each of the 18F labeled nitroimidzaoles was quite uniform and consistent with that of nitroimidazoles previously studied. These results suggest the need for a suitable animal model to evaluate their potential as in vivo markers of hypoxic tissue in the brain.

Multimillicurie preparation of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose via nucleophilic displacement with fluorine‐18 labelled fluoride. 1. Purification and quality control procedures

AbstractHigh performance liquid chromatography (HPLC) has been utilized for the preparation of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose (18F‐2FDG) in 98.3 ± 1.5% radiochemical purity. Employing an enriched water target for fluoride‐18 labelled fluoride ion production, the time required for synthesis and purification of the finished product averaged 150 minutes from end of bombardment (EOB). The average radiochemical yield of the pharmaceutical product at EOB was 18%.

Synthesis of 11C- dl-tryptophan and its purification using high-pressure liquid chromatography

Carbon-11- dl-tryptophan has been produced from 11C-cyanide using a modified Bücherer-Strecker technique for synthesis and a high-pressure liquid chromatographic system for purification. More than 80 preparations have been run with an average radiochemical yield of 50% and synthesis and purification times of about 28 min. These modifications have significantly increased the level of 11C-tryptophan activity which is available for clinical use per mCi of 11C-cyanide.

Synthesis of 14C-Meglumine Salicylate and Its Disposition in Humans after Oral Administration

The synthesis of 14C-meglumine salicylate was accomplished by heating 14C-meglumine with salicylic acid, in equimolar ratios, in 2-propanol. The average radiochemical yield was 97.5%. Ten healthy adult male volunteers were given 1.2g of the compound orally. Five took 1.2g of 1-deoxy-l-[14C]-methylamino-D-glucitol salicylate (containing about 47μCi), and five others took 1.2g of 1-deoxy-l-methylamino-D-[U-14C]-glucitol salicylate (containing about 45μCi). Urine and feces were collected for 5 days, and blood was sampled for 24hr. The peak urinary excretion of meglumine and/or its metabolites occurred between 4 and 8hr after administration (about 7.2% of the administered dose). Meglumine was excreted primarily in the feces (72.4% over 5 days) and, to a smaller extent, in urine (21.3% over 5days). No activity was detected in blood. The excretion rate and percentage excreted were the same for both groups of subjects, suggesting that meglumine was not metabolized by N-demethylation or conversion to carbon dioxide. The highest blood salicylate level, 44.4±1.9μg/ml, was observed 1hr after administration. Urinary levels of salicylic acid and its metabolites were observed to be at a maximum at 8hr. Total salicylate recovery was 94.7±1.5% in 48hr. Salicyluric acid was the major metabolite, accounting for 69.5±3.6% of the dose. Salicylic acid accounted for 6.8±1.2%.