No-carrier-added synthesis of 3-[ 18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol. A potential PET agent for detecting hypoxic but viable tissues

Abstract

Four different approaches towards the synthesis of [ 18F]FMISO have been studied. The first approach was based on the reaction of epoxide 4 and [ 18F]fluoride. Both specific activity and radiochemical yield (<1%) for [ 18F]FMISO were low. Two new approaches, starting with compounds 8 and 9, have failed to give [ 18F]FMISO. The fourth approach, based on the reaction of [ 18F]epifluorohydrin 10, prepared from Tosylate 13 and [ 18F]KF/Kryptofix 222, has provided a reliable, no-carrier added synthesis of [ 18F]FMISO. The product was obtained in a radiochemical yield of 7–12% at end-of-synthesis (based on [ 18F]fluoride) with a specific activity of >400 Ci/mmol and a synthesis time of 1.5 h. Preliminary PET studies suggest that [ 18F]FMISO may be a promising tracer for delineation of ischemic but viable myocardium.