@article{oai:repo.qst.go.jp:00047633,
 author = {Kawamura, Kazunori and Kumata, Katsushi and Takei, Makoto and Furutsuka, Kenji and Hashimoto, Hiroki and Ito, Takehito and Shiomi, Satoshi and Fujishiro, Tomoya and Watanabe, Ryuji and Igarashi, Nobuyuki and Muto, Masatoshi and Yamasaki, Tomoteru and Yui, Joji and Xie, Lin and Hatori, Akiko and Zhang, Yiding and Nemoto, Kazuyoshi and Fujibayashi, Yasuhisa and Zhang, Ming-Rong and 河村 和紀 and 熊田 勝志 and 武井 誠 and 古塚 賢士 and 橋本 裕輝 and 伊藤 岳人 and 潮見 聡 and 藤代 智也 and 渡辺 竜二 and 五十嵐 延行 and 武藤 正敏 and 山崎 友照 and 由井 譲二 and 謝 琳 and 羽鳥 晶子 and 張 一鼎 and 根本 和義 and 藤林 康久 and 張 明栄},
 issue = {7},
 journal = {Nuclear Medicine and Biology},
 month = {Jun},
 note = {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.},
 pages = {445--453},
 title = {Efficient radiosynthesis and non-clinical safety tests of the TSPO radioprobe [18F]FEDAC: Prerequisites for clinical application},
 volume = {43},
 year = {2016}
}