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

The dependence of the radiochemical yield of [F-18]fluoromisonidazole (1) o n different reaction parameters such as reaction time, temperature and amou nt of precursor was investigated for the nucleophilic substitution of tosyl ate by [F-18]fluoride and subsequent hydrolysis of the protecting group on 1-(2'-nitro-1'-imidazolyl)-2-O-terrahydropyranyl-3-O-toluenesulfonylpropane diol as the precursor molecule (2) Highest yields (86%+/-6%) were obtained using 10 mg (2) at 100 degrees C for 10 minutes, whereas both at 80 and 120 degrees C the yields were lower (46%+/-11% and 29%+/-14%, respectively). A rapid decrease of the yield was observed when the reaction time exceeded 1 5 minutes, i.e., at 100 degrees C using 5 mg (2) the radiochemical yield de creased from 61%+/-8% at 15 minutes to 18%+/-10% at 60 minutes.