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.
|
Authors | Takayuki Ohkubo, Yusuke Kurihara, Masanao Ogawa, Nobuki Nengaki, Masayuki Fujinaga, Wakana Mori, Katsushi Kumata, Masayuki Hanyu, Kenji Furutsuka, Hiroki Hashimoto, Kazunori Kawamura, Ming-Rong Zhang |
Journal | EJNMMI radiopharmacy and chemistry
(EJNMMI Radiopharm Chem)
Vol. 6
Issue 1
Pg. 23
(Jul 10 2021)
ISSN: 2365-421X [Electronic] England |
PMID | 34245396
(Publication Type: Journal Article)
|
Copyright | © 2021. The Author(s). |