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

Abstract

Background [18F]Fluoromisonidazole ([18F]FMISO) and 1-[18F]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 ([18F]PM-PBB3 or [18F]APN-1607) are clinically used radiotracers for imaging for hypoxia and tau pathology, respectively. Both radiotracers were produced by direct [18F]fluorination using the corresponding tosylate precursors 1 or 2 and [18F]F−, followed by the removal of protecting groups. In this study, we synthesized [18F]FMISO and [18F]PM-PBB3 by [18F]fluoroalkylation using [18F]epifluorohydrin ([18F]5) for clinical applications. Results First, [18F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [18F]F− and was purified by distillation. Subsequently, [18F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for 18F-labeling, and each reaction mixture was refined by semipreparative high-performance liquid chromatography and formulation to obtain the [18F]FMISO or [18F]PM-PBB3 injection. All synthetic sequences were performed using an automated 18F-labeling synthesizer. The [18F]FMISO thus obtained showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis; n = 8) with appropriate radiochemical yield based on [18F]F− (26 ± 7.5% at the end of irradiation with decay-corrected; n = 8). [18F]PM-PBB3 thus obtained showed sufficient radioactivity (0.79 ± 0.10 GBq; n = 11) with appropriate radiochemical yield based on [18F]F− (16 ± 3.2% at the end of irradiation with decay-corrected; n = 11). Conclusions Both [18F]FMISO and [18F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by [18F]fluoroalkylation using [18F]5.