Automated radiosynthesis of two (18)F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [(18)F]FMISO and [(18)F]PM-PBB3, via [(18)F]epifluorohydrin

BACKGROUND: [(18)F]Fluoromisonidazole ([(18)F]FMISO) and 1-[(18)F]fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([(18)F]PM-PBB3 or [(18)F]APN-1607) are clinically used radiotracers for imaging hypoxia and tau pathology, respectively. Both radiotracers were produced by direct (18)F-fluorination using the corresponding tosylate precursors 1 or 2 and [(18)F]F(−), followed by the removal of protecting groups. In this study, we synthesized [(18)F]FMISO and [(18)F]PM-PBB3 by (18)F-fluoroalkylation using [(18)F]epifluorohydrin ([(18)F]5) for clinical applications. RESULTS: First, [(18)F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [(18)F]F(−) and was purified by distillation. Subsequently, [(18)F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for (18)F-labeling, and each reaction mixture was purified by preparative high-performance liquid chromatography and formulated to obtain the [(18)F]FMISO or [(18)F]PM-PBB3 injection. All synthetic sequences were performed using an automated (18)F-labeling synthesizer. The obtained [(18)F]FMISO showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis (EOS); n = 8) with appropriate radiochemical yield based on [(18)F]F(−) (26 ± 7.5 % at EOS, decay-corrected; n = 8). The obtained [(18)F]PM-PBB3 also showed sufficient radioactivity (0.79 ± 0.10 GBq at EOS; n = 11) with appropriate radiochemical yield based on [(18)F]F(−) (16 ± 3.2 % at EOS, decay-corrected; n = 11). CONCLUSIONS: Both [(18)F]FMISO and [(18)F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by (18)F-fluoroalkylation using [(18)F]5. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41181-021-00138-9.