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 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 purified by preparative high-performance liquid chromatography and formulated to obtain the [¹⁸F]FMISO or [¹⁸F]PM-PBB3 injection. All synthetic sequences were performed using an automated ¹⁸F-labeling synthesizer. The obtained [¹⁸F]FMISO showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis (EOS); n = 8) with appropriate radiochemical yield based on [¹⁸F]F^- (26 ± 7.5 % at EOS, decay-corrected; n = 8). The obtained [¹⁸F]PM-PBB3 also showed sufficient radioactivity (0.79 ± 0.10 GBq at EOS; n = 11) with appropriate radiochemical yield based on [¹⁸F]F^- (16 ± 3.2 % at EOS, 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.

SUBMITTER: Ohkubo T 

PROVIDER: S-EPMC8272768 | biostudies-literature |

REPOSITORIES: biostudies-literature