@article{oai:repo.qst.go.jp:00045986,
 author = {Kawamura, Kazunori and Yamasaki, Tomoteru and Konno, Fujiko and Yui, Joji and Hatori, Akiko and Yanamoto, Kazuhiko and Wakizaka, Hidekatsu and Ogawa, Masanao and Yoshida, Yuichiro and Nengaki, Nobuki and Fukumura, Toshimitsu and Zhang, Ming-Rong and 河村 和紀 and 山崎 友照 and 昆野 富士子 and 由井 譲二 and 羽鳥 晶子 and 柳本 和彦 and 脇坂 秀克 and 小川 政直 and 吉田 勇一郎 and 念垣 信樹 and 福村 利光 and 張 明栄},
 issue = {2},
 journal = {Bioorganic & Medicinal Chemistry},
 month = {Dec},
 note = {The purpose of this study was to synthesize two new positron emission tomography (PET) probes,N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[18F]fluoroethoxy-9-oxo-4-acridine carboxamide ([18F]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2-[18F]fluoroethoxy)-
6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethyl}phenylcarbamoyl)-4,5-imethoxyphenyl]amide ([18F]4),andtoevaluate thepotentialof thesePETprobes for assessing thefunctionoftwomajor drugefflux transporters,P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). [18F]3 and [18F]4 were synthesized by
18F-alkylation of each O-desmethyl precursor with [18F]2-fluoroethyl bromide for injection as PET probes. In vitroaccumulation assayshowed that treatmentwith P-gp/BCRPinhibitors (1 and2) enhanced the intracellular accumulation capacity of P-gp- and BCRP-overexpressing MES-SA/Dx5 cells. In PET studies, the uptake (AUCbrain [0–60 min]) of [18F]3 and [18F]4 in wild-type mice co-injected with 1 were approximately sevenfold higher than that in wild-typemice, and the uptake of [18F]3 and [18F]4 in P-gp/Bcrp knockout mice were eightto ninefold higher than that in wild-typemice. The increased uptake of [18F]3 and [18F]4 was similar to that of
parent compounds([11C]1 and [11C]2) previously described, indicating that radioactivity levels in the brain after injection of [18F]3 and [18F]4 are related to the function of drug efflux transporters. Also, these results suggest that the structural difference between parent compounds ([11C]1 and [11C]2) and fluoroethyl analogs ([18F]3 and [18F]4) do not obviously affect the potency against drug efflux transporters. Inmetabolite analysis of mice, the unchanged form in the brain and plasma at 60min after co-injection of [18F]4 plus 1 were higher (95% for brain; 81% for plasma) than that after co-injection of [18F]3 plus 1. [18F]4 is a promising PET probe to assess the function of drug efflux transporters.},
 pages = {861--870},
 title = {Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters},
 volume = {19},
 year = {2010}
}