Fully automated radiosynthesis of [18F]Fluoromisonidazole with single neutral alumina column purification: optimization of reaction parameters

1-H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO), is the most used hypoxia-imaging agent in oncology and we have recently reported a fully automated procedure for its synthesis using the Nuclear Interface FDG module and a single neutral alumina column for purification. Using 1-(2′-nitro-1′-imidazolyl)-2-O-tetra-hydropyranyl-3-O-toluenesulfonylpropanediol (NITTP) as the precursor, we have investigated the yield of [¹⁸F]FMISO using different reaction times, temperatures, and the amount of precursor. The overall yield was 48.4 ± 1.2% (n = 3), (without decay correction) obtained using 10 mg NITTP with the radio-fluorination carried out at 145 °C for 3 min followed by acid hydrolysis for 3 min at 125 °C in a total synthesis time of 32 ± 1 min. Increasing the precursor amount to 25 mg did not improve the overall yield under identical reaction conditions, with the decay uncorrected yield being 46.8 ± 1.6% (n = 3), but rather made the production less economical. It was also observed that the yield increased linearly with the amount of NITTP used, from 2.5 to 10 mg and plateaued from 10 to 25 mg. Radio-fluorination efficiency at four different conditions was also compared. It was also observed by radio thin layer chromatography (radio-TLC) that the duration of radio-fluorination of NITTP, not the radio-fluorination temperature favoured the formation of labeled thermally degraded product, but the single neutral alumina column purification was sufficient enough to obtain [¹⁸F]FMISO devoid of any radiochemical as well as cold impurities.