RAPID SYNTHESIS AND USE OF 18F-FLUOROMISONIDAZOLE AND ANALOGS

摘要

The present invention involves a rapid synthesis of 18 F-FMISO and analogs thereof. New precursors such as 1-(2'-nitro-1'-imidazolyl)-2-O-acetyl-3-O-tosylpropanol, glycerol-1,3-ditosylate-2-O-acetylate, 1-(2'-nitro-1'-imidazolyl)-2,3-O-diacetyl-4-O-tosylbutanol and threitol 1,4-di-tosylate-2,3-O-diacetylate, are also important aspects of the invention. A further aspect of the invention is the development of a hydrophilic PET ligand to image tumor hypoxia. Erythrotosyl analogue of 2-nitroimidazone (Ts-ETNIM) was prepared from a mixture of 2-nitromidazole, ditosylthreitol and cesium carbonate at 60 °C for 1 hr. Ts-ETNIM was isolated at 70 % yield. [18F]fluoroerythronitroimidazole (FETNIM) was then prepared from Ts-ETNIM and K18F/kryptofix®. The yield for [18F]FETNIM was 26-30 % (60 min, decay corrected). Results of biodistribution and PET studies indicate that [18F]FETNIM has the potential to detect tumor hypoxia and is indicated to be less neurotoxic.