会議発表用資料 Development of Imaging Agents for Glutamine Transporter: In silico Binding Assay and Synthesis of Derivatives Derived from Tamoxifen and Tetrahydrobenzopyran

Yamaguchi, Hiroshi  ,  Sumi , Takuya  ,  Kang , Jiyoung  ,  Yamashiro, Keiichi  ,  Okada, Maki  ,  Tateno, Masaru  ,  Kato, Katsuhiko  ,  Ming-Rong, Zhang  ,  Watanabe, Hirohisa  ,  Sobue, Gen

2017-05-18
内容記述
Objectives: The positoron emission tomography (PET) imaging is a useful method to investigate biological functions of receptor and transporter in CNS. The detection of the functional changes would also lead us to an early diagnosis of various brain diseases. In order to develope useful imaging agents that bind to glutamine transporter, we have examined tamoxifen delivatives that are known to affect the functions of glutamine transporter, by labelling some of the compounds with [18F] F- or [11C] CH3I, [11C] methyl trifluoromethanesulfonate. Methods: First, we performed an in silico binding assay by generating various derivetives of tamoxifen and tetrahydrobenzopyran, employing our protein-ligand docking calculation. Next, we synthesized the precursors of the obtianed delivatives: The derivatives derived from tamoxifen were conjugated to those of ketone by using the McMurry coupling reaction. The derivatives of tetrahydrobenzopyran were synthesized from diketone components and cyano analogues. After purification of the reaction mixture with the flash column chromatography procedure and recrystallization, we obtained the precursors, for labelling, which were reacted with [18F] F-or [11C] CH3I, [11C] methyl triflate on automatic synthesis system. Results: In the present study, we synthesized the 11C- or 18F-labelled derivatives derived from tamoxifen and tetrahydrobenzopyran. Currently, we are attempting to improve the yields and the resultant compounds in the labelling reaction. Conclusions: We have conducted an in silico binding assay and synthesized the labelled derivatives of tamoxifen and tetrahydrobenzopyran, that are thus possible ligands of glutamate transporter. The experiments using an in vivo small animal imaging device are also ongoing in our group.
22nd International symposium on radiopharmaceutical science (ISRS)

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