@article{oai:repo.qst.go.jp:00044203,
 author = {Zhang, Ming-Rong and Maeda, Jun and Ito, Takehito and Okauchi, Takashi and Ogawa, Masanao and Noguchi, Junko and Suhara, Tetsuya and Halldin, Christer and Suzuki, Kazutoshi and 張 明栄 and 前田 純 and 岡内 隆 and 小川 政直 and 須原 哲也 and ハルディン クリスタ and 鈴木 和年},
 journal = {Bioorganic & Medicinal Chemistry},
 month = {Dec},
 note = {N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide ([18F]2)is a potent ligand (IC50,1.71 nM) for peripheral benzodiazepine receptor (PBR).However,in vivo evaluation on rodents and primates showed that this ligand was unstable and rapidly metabolized to [18F]F- by defluorination of the [18F]fluoromethyl moiety. In this study, we designed a deuterium-substituted analogue, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide ([18F]5) as a radioligand for PBR to reduce the in vivo metabolic rate of the non-deuterated [18F]2. The design principle was based on the hypothesis that the deuterium substitution may reduce the rate of defluorination initiated by cleavage of the C-H bond without altering the binding affinity for PBR. The non-radioactive 5 was prepared by reacting diiodomethane-d2 (CD2I2, 6) with a phenol precursor 7, followed by treatment with tetrabutylammonium fluoride. The ligand [18F]5 was synthesized by the alkylation of 7 with [18F]fluoromethyl iodide-d2 ([18F]FCD2I, [18F]9).  Compound 5 displayed a similar in vitro affinity to PBR (IC50,1.90 nM) with 2.  In vivo evaluation demonstrated that [18F]5 was metabolized by defluorination to [18F]F-as a main radioactive component, but its metabolic rate was slower than that of [18F]2 in the brain of mice. The deuterium substitution decreased the radioactivity level of [18F]5 in the bone of mouse, augmented by the percentage of specific binding to PBR in the rat brain determined by ex vivo autoradiography. However,the PET image of[18F]5 for monkey brain showed high radioactivity in the brain and skull, suggesting a possible species difference between rodents and primates.},
 pages = {1811--1818},
 title = {Synthesis and evaluation of N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoromethoxy-d2-5-methoxybenzyl)acetamide:a deuterium-substituted radioligand for peripheral benzodiazepine receptor},
 volume = {13},
 year = {2005}
}