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Simple method for introduction of 3-[18F]fluoro-2-hydroxypropyl group and application for synthesis of 18F-labeled ligand
https://repo.qst.go.jp/records/72334
https://repo.qst.go.jp/records/72334b08c6876-0791-44b8-b03c-8214ef3d20b3
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-05-24 | |||||
| タイトル | ||||||
| タイトル | Simple method for introduction of 3-[18F]fluoro-2-hydroxypropyl group and application for synthesis of 18F-labeled ligand | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Fujinaga, Masayuki
× Fujinaga, Masayuki× Ohkubo, Takayuki× Yamasaki, Tomoteru× Zhang, Yiding× Hatori, Akiko× Kumata, Katsushi× Nengaki, Nobuki× Zhang, Ming-Rong× 藤永 雅之× 大久保 崇之× 山崎 友照× 張 一鼎× 羽鳥 晶子× 熊田 勝志× 念垣 信樹× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: 18F-Fluoroalkylation is a useful method for introduction of fluorine-18 into molecules containing NH, OH, and SH-groups, analogously to the 11C-methylation with [11C]CH3I. Moreover, introduction of [18F]fluoroalkyl group could sometimes lead to significant improvement of in vitro properties and in vivo behaviors. We have developed a 18F-fluoroalkylation route with [18F]FMeOTf, [18F]FEtBr or [18F]FPrBr etc., which could be purified by simple distillation using an automated synthesis system [1]. Furthermore, we have routinely produced clinically useful 18F-ligands, such as [18F]FMeNER-d2, [18F]FEDAC and [18F]FEtPE2I by using of these agents. To further extend application of this technique, here, we developed a simple method for introducing 3-[18F]fluoro-2-hydroxypropyl group into phenol precursors with [18F]epifluorohydrin ([18F]2) and applied the method to synthesize 18F-labeled ligands. Methods: Glycidyl tosylate 1 was synthesized by reaction of glycidol and tosyl chloride with K2CO3. Unlabeled 3 and 4 were prepared by reaction of corresponding phenol derivatives and 2 in the presence of base. [18F]3 and [18F]4 was synthesized by reacting with phenol precursors with [18F]2 using a homemade automated synthesis system. Results: We used 4-phenylphenol as a model substrate. After 18F-fluorination of 1 (10 L) with [18F]fluoride ion in 1,2-dichlorobenzene at 130 oC, [18F]2 (b.p. 85-86 oC) was formed and then purified by distillation into a DMF solution containing desmethyl precursor (1 mg) and NaOH for 2 min. The radiochemical yield of [18F]2 was estimated to be 80% (based on the [18F]fluoride ion, corrected for decay). After the trapping, this reaction mixture was heated at 130 oC for 20 min. By purification for the reaction mixture using semi-preparative HPLC, [18F]3 was obtained with a synthesis time of 68 min. As application of this reagent for development of 18F-labeled ligand, [18F]4 as a new TSPO ligand was synthesized by reaction of the corresponding precursor with [18F]2. After HPLC purification and formulation, [18F]4 was obtained with 5% radiochemical yield (isolated-yield). Conclusion: We have successfully developed a convenient and reliable technique for producing [18F]2 using a home-made automated synthesis system. This reagent has been used to introduce 3-[18F]fluoro-2-hydroxypropyl group into PET ligand candidates, such as [18F]4. This novel PET ligand is now available for evaluation in mice or rat and improvement for the radiochemical yield is on progress. Acknowledgements: References: [1] Zhang M-R, et al, Curr Top Med Chem., 2007, 7(18), 1817-1828. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 22nd International symposium on radiopharmaceutical science (ISRS) | |||||
| 発表年月日 | ||||||
| 日付 | 2017-05-15 | |||||
| 日付タイプ | Issued | |||||
