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

• Main Authors: Takayuki Ohkubo (Author), Yusuke Kurihara (Author), Masanao Ogawa (Author), Nobuki Nengaki (Author), Masayuki Fujinaga (Author), Wakana Mori (Author), Katsushi Kumata (Author), Masayuki Hanyu (Author), Kenji Furutsuka (Author), Hiroki Hashimoto (Author), Kazunori Kawamura (Author), Ming-Rong Zhang (Author)
• Format: Book
• Published: SpringerOpen, 2021-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s41181-021-00138-9; 2365-421X
• Keywords: 18F; [18F]Epifluorohydrin; [18F]FMISO; [18F]PM-PBB3; Positron emission tomography (PET); Medical physics. Medical radiology. Nuclear medicine; R895-920; Therapeutics. Pharmacology; RM1-950
• Source: EJNMMI Radiopharmacy and Chemistry, Vol 6, Iss 1, Pp 1-13 (2021)

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.