Application of radioisotopes in inflammation.

Since the discovery of artificially produced radioisotopes in the 1930's, an estimated 10-12 million nuclear medicine diagnostic and therapeutic procedures are currently performed each year only in the United States. Gamma emission imaging has been successfully applied to almost every organ of the body (brain, bone, heart, kidney, lung, neuroreceptors) as well as sites of inflammation, atherosclerosis, and thrombosis. FDG-PET has been used in some of the inflammatory diseases as well. On the other hand, both alpha- and beta-emitting isotopes have been evaluated for brachytherapy of rheumatoid diseases, each with different radiobiological effectiveness. The current status of radionuclides for imaging, therapy and research studies of inflammatory processes is reviewed here and a look into the future directions is described at the conclusion.

Synthesis and in vitro antifungal and cytotoxicity evaluation of substituted 4,5-dihydronaphtho[1,2-d][1,2,3]thia(or selena)diazoles.

Unsubstituted 4,5-dihydronaphtho[1,2-d][1,2,3]thia (or selena)diazoles (2a, 2b), prepared from the semicarbazone (1a), were nitrated using fuming nitric acid at 0 degrees C to yield various mono-nitrated dihydronaphthalenes (3a-3e). Related sulfamoyl derivatives (4a, 4b) were prepared using chlorosulfonic acid, followed by the addition of ammonia solution. Synthesis of 6,9-dimethoxy-4,5-dihydronaphtho[1,2-d][1,2,3]thiadiazole derivative (2c) was performed using 5,8-dimethoxy-alpha-tetralone semicarbazone (1b) and thionylchloride at low temperature. At 10 ppm concentration, all compounds showed low toxicity (higher than 80% survival) on brine shrimps, while at 100 ppm concentration compounds 2d, 3d, and 4b exhibited toxicity (less than 60% survival). Compounds 3a, 3e, and especially 4a showed significant antifungal activity against Cryptococcus neoformans. Compound 4a, while being the most active antifungal agent in this series, possessed low toxicity.

Synthesis and in vitro antifungal and cytotoxicity evaluation of thiazolo-4H-1,2,4-triazoles and 1,2,3-thiadiazolo-4H-1,2,4-triazoles.

The increasing clinical importance of drug-resistant fungal pathogens has lent additional urgency to microbiological and antifungal research. Various thiazolo(or 1,2,3-thiadiazolo)thiosemicarbazides (2a-2e), 3-thiono-1,4-dihydrotriazolothiazoles-(or 1,2,3-thiadiazoles) (3a-3e), their related substituted thio-4H-1,2,4-triazoles (4a-4p) and sulfones (5a-5o) were synthesized. Most of the compounds tested for antifungal activity exhibited significant effects against Cryptococcus neoofrmans and Sacchromyces cerevisiae at MIC ranges of 0.53 to 12.5 micrograms/mL, whereas their activities were moderate against Candida albicans and weak against Aspergillus fumigatus. At 10 ppm concentration, all compounds showed low toxicity on brine shrimps (higher than 80% survival), except compounds 4c and 2c. At 100 ppm concentration most of the compounds showed toxicity except compounds 2b, 2e, 3c, 3d, 3e, and 4e. Compounds 4b, 4c, and 4h showed in vitro cytotoxicity against Kbalb cell lines and compounds 4c and 4g against 143B cell lines at 0.1 mM concentration.

A new method for one-step, no-carrier-added synthesis of cholesteryl 4-[18F]-fluorobenzoate ([18F]-CFB), a radiotracer used in detection of adrenal malignancies.

PURPOSE: Cholesteryl 4-[(18)F]-fluorobenzoate, a potential radiotracer used for adrenal and ovarian imaging, was prepared in no-carrier-added form from cholesteryl 4-N,N,N-trimethylanilinium trifluoromethanesulfonate. METHODS: The reaction was performed in one step using Kryptofix2.2.2/[(18)F], carbonate as the counter ion and dimethyl sulfoxide as the solvent at 110 degrees C. Purification was performed using commercially available C(18) and Si Sep-Paks. RESULTS: Column purification afforded the desired compound in 75-85 % radiochemical yield (EOS) with a specific activity about 74 KBq/mmole in about 20 minutes, with greater than 95% radiochemical and chemical purity (HPLC and TLC analysis). CONCLUSIONS: This compound was prepared through a novel method which can be easily performed at distant locations from the main radionuclide production centers using Sep-Paks. The biodistribution of this compound in mice was confirmed to be similar to that reported in the literature.