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

BACKGROUND

[F]Fluoromisonidazole ([F]FMISO) and 1-[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 ([F]PM-PBB3 or [F]APN-1607) are clinically used radiotracers for imaging hypoxia and tau pathology, respectively. Both radiotracers were produced by direct F-fluorination using the corresponding tosylate precursors 1 or 2 and [F]F, followed by the removal of protecting groups. In this study, we synthesized [F]FMISO and [F]PM-PBB3 by F-fluoroalkylation using [F]epifluorohydrin ([F]5) for clinical applications.

RESULTS

First, [F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [F]F and was purified by distillation. Subsequently, [F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for F-labeling, and each reaction mixture was purified by preparative high-performance liquid chromatography and formulated to obtain the [F]FMISO or [F]PM-PBB3 injection. All synthetic sequences were performed using an automated F-labeling synthesizer. The obtained [F]FMISO showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis (EOS); n = 8) with appropriate radiochemical yield based on [F]F (26 ± 7.5 % at EOS, decay-corrected; n = 8). The obtained [F]PM-PBB3 also showed sufficient radioactivity (0.79 ± 0.10 GBq at EOS; n = 11) with appropriate radiochemical yield based on [F]F (16 ± 3.2 % at EOS, decay-corrected; n = 11).

CONCLUSIONS

Both [F]FMISO and [F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by F-fluoroalkylation using [F]5.