ヒグチ　ケイ   Higuchi Kei   樋口　慧    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Development and radiosynthesis of the first 18 F-labeled inhibitor of monocarboxylate transporters (MCTs).
掲載誌名	正式名：Journal of labelled compounds & radiopharmaceuticals
掲載区分	国外
巻・号・頁	62(8),pp.411-424
著者・共著者	Masoud Sadeghzadeh,Rareş-Petru Moldovan,Steffen Fischer,Barbara Wenzel,Friedrich-Alexander Ludwig,Rodrigo Teodoro,Winnie Deuther-Conrad,Shirisha Jonnalagadda,Sravan K Jonnalagadda,Emilis Gudelis,Algirdas Šačkus,Kei Higuchi,Vadivel Ganapathy,Venkatram R Mereddy,Lester R Drewes,Peter Brust
発行年月	2019/06/30
概要	Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumor development and progression. Their expression levels are related to clinical disease prognosis. Accordingly, both MCTs are promising drug targets for treatment of a variety of human cancers. The noninvasive imaging of these MCTs in cancers is regarded to be advantageous for assessing MCT-mediated effects on chemotherapy and radiosensitization using specific MCT inhibitors. Herein, we describe a method for the radiosynthesis of [18 F]FACH ((E)-2-cyano-3-{4-[(3-[18 F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylic acid), as a novel radiolabeled MCT1/4 inhibitor for imaging with PET. A fluorinated analog of α-cyano-4-hydroxycinnamic acid (FACH) was synthesized, and the inhibition of MCT1 and MCT4 was measured via an L-[14 C]lactate uptake assay. Radiolabeling was performed by a two-step protocol comprising the radiosynthesis of the intermediate (E)/(Z)-[18 F]tert-Bu-FACH (tert-butyl (E)/(Z)-2-cyano-3-{4-[(3-[18 F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylate) followed by deprotection of the tert-butyl group. The radiofluorination was successfully implemented using either K[18 F]F-K2.2.2 -carbonate or [18 F]TBAF. The final deprotected product [18 F]FACH was only obtained when [18 F]tert-Bu-FACH was formed by the latter procedure. After optimization of the deprotection reaction, [18 F]FACH was obtained in high radiochemical yields (39.6 ± 8.3%, end of bombardment (EOB) and radiochemical purity (greater than 98%).
DOI	10.1002/jlcr.3739
PMID	31017677