Preparation of [¹⁸F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters

Abstract

The dependence of the radiochemical yield of [¹⁸F]fluoromisonidazole (1) on different reaction parameters such as reaction time, temperature and amount of precursor was investigated for the nucleophilic substitution of tosylate by [¹⁸F]fluoride and subsequent hydrolysis of the protecting group on 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonylpropanediol as the precursor molecule (2). Highest yields (86%±6%) were obtained using 10 mg (2) at 100°C for 10 minutes, whereas both at 80 and 120°C the yields were lower (46%±11% and 29%±14%, respectively). A rapid decrease of the yield was observed when the reaction time exceeded 15 minutes, i.e., at 100°C using 5 mg (2) the radiochemical yield decreased from 61%±8% at 15 minutes to 18%±10% at 60 minutes.