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Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters
https://repo.qst.go.jp/records/45986
https://repo.qst.go.jp/records/4598652e9636b-8564-4761-b7b9-4fa9d286a23b
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-01-21 | |||||
| タイトル | ||||||
| タイトル | Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Kawamura, Kazunori
× Kawamura, Kazunori× Yamasaki, Tomoteru× Konno, Fujiko× Yui, Joji× Hatori, Akiko× Yanamoto, Kazuhiko× Wakizaka, Hidekatsu× Ogawa, Masanao× Yoshida, Yuichiro× Nengaki, Nobuki× Fukumura, Toshimitsu× Zhang, Ming-Rong× 河村 和紀× 山崎 友照× 昆野 富士子× 由井 譲二× 羽鳥 晶子× 柳本 和彦× 脇坂 秀克× 小川 政直× 吉田 勇一郎× 念垣 信樹× 福村 利光× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. |
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| 書誌情報 |
Bioorganic & Medicinal Chemistry 巻 19, 号 2, p. 861-870, 発行日 2010-12 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0968-0896 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.bmc.2010.12.004 | |||||
