WEKO3
アイテム
Efficient radiosynthesis and non-clinical safety tests of the TSPO radioprobe [18F]FEDAC: Prerequisites for clinical application
https://repo.qst.go.jp/records/47633
https://repo.qst.go.jp/records/47633d288289d-f795-4de8-b1fc-ae56c4d272b2
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-02-08 | |||||
| タイトル | ||||||
| タイトル | Efficient radiosynthesis and non-clinical safety tests of the TSPO radioprobe [18F]FEDAC: Prerequisites for clinical application | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Kawamura, Kazunori
× Kawamura, Kazunori× Kumata, Katsushi× Takei, Makoto× Furutsuka, Kenji× Hashimoto, Hiroki× Ito, Takehito× Shiomi, Satoshi× Fujishiro, Tomoya× Watanabe, Ryuji× Igarashi, Nobuyuki× Muto, Masatoshi× Yamasaki, Tomoteru× Yui, Joji× Xie, Lin× Hatori, Akiko× Zhang, Yiding× Nemoto, Kazuyoshi× Fujibayashi, Yasuhisa× Zhang, Ming-Rong× 河村 和紀× 熊田 勝志× 武井 誠× 古塚 賢士× 橋本 裕輝× 伊藤 岳人× 潮見 聡× 藤代 智也× 渡辺 竜二× 五十嵐 延行× 武藤 正敏× 山崎 友照× 由井 譲二× 謝 琳× 羽鳥 晶子× 張 一鼎× 根本 和義× 藤林 康久× 張 明栄 |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | INTRODUCTION: [18F]FEDAC ([18F]1) has potent binding affinity and selectivity for translocator protein (18kDa, TSPO), and has been used to noninvasively visualize neuroinflammation, lung inflammation, acute liver damage, nonalcoholic fatty liver disease, and liver fibrosis. We had previously synthesized [18F]1 in two steps: (i) preparation of [18F]fluoroethyl bromide and (ii) coupling of [18F]fluoroethyl bromide with the appropriate precursor (2) for labeling. In this study, to clinically utilize [18F]1 as a PET radiopharmaceutical and to transfer the production technique of [18F]1 to other PET centers, we simplified its preparation by using a direct, one-step, tosyloxy-for-fluorine substitution. We also performed an acute toxicity study as a major non-clinical safety test, and determined radiometabolites using human liver microsomes. METHODS: [18F]1 was prepared via direct 18F-fluorination by heating the corresponding tosylated derivative (3) with [18F]fluoride as its Kryptofix 222 complex in dimethyl sulfoxide at 110°C for 15min, following by HPLC purification. Non-clinical safety tests were performed for the extended single-dose toxicity study in rats, and for the in vitro metabolite analysis with human liver microsomal incubation. RESULTS: High quality batches of [18F]1, compatible with clinical applications, were obtained. At the end of irradiation, the decay-corrected radiochemical yield of [18F]1 using 1 and 5mg of precursor based on [18F]fluoride was 18.5±7.9% (n=10) and 52.0±5.8% (n=3), respectively. A single-dose of [18F]1 did not show toxicological effects for 14 days after the injection in male and female rats. In human liver microsomal incubations, [18F]1 was easily metabolized to [18F]desbenzyl-FEDAC ([18F]10) by CYPs (4.2% of parent compound left 60min after incubation). CONCLUSION: We successfully synthesized clinical grade batches of [18F]1 and verified the absence of innocuity of this radiotracer. [18F]1 will be used to first-in-human studies in our facility. |
|||||
| 書誌情報 |
Nuclear Medicine and Biology 巻 43, 号 7, p. 445-453, 発行日 2016-06 |
|||||
| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 27183465 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.nucmedbio.2016.04.004 | |||||
