WEKO3
アイテム
Synthesis and evaluation of [11C]XR9576 to assess the function of drug efflux transporters using PET
https://repo.qst.go.jp/records/45806
https://repo.qst.go.jp/records/458068667d806-cdc1-4b74-be03-85478dab598c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-06-16 | |||||
| タイトル | ||||||
| タイトル | Synthesis and evaluation of [11C]XR9576 to assess the function of drug efflux transporters using PET | |||||
| 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× Konno, Fujiko× Yui, Joji× Yamasaki, Tomoteru× Hatori, Akiko× Yanamoto, Kazuhiko× Wakizaka, Hidekatsu× Takei, Makoto× Nengaki, Nobuki× Fukumura, Toshimitsu× Zhang, Ming-Rong× 河村 和紀× 昆野 富士子× 由井 譲二× 山崎 友照× 羽鳥 晶子× 柳本 和彦× 脇坂 秀克× 武井 誠× 念垣 信樹× 福村 利光× 張 明栄 |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objective XR9576 (tariquidar) is an anthranilic acid derivative and potent P-glycoprotein (P-gp) inhibitor. XR9576 has undergone phase I and II studies as combined chemotherapy against cancer. XR9576 has been developed as a useful therapeutic agent but not as a PET probe. We therefore developed [11C]XR9576 as a PET probe and assessed whether PET studies using [11C]XR9576 are a promising approach to assess P-gp function primarily. Methods We synthesized [11C]XR9576 by methylation of 7-O-desmethyl XR9576 with [11C]methyl iodide. In in vivo tissue distribution, the effects of co-injection with XR9576 on the uptake of [11C]XR9576 in mice were investigated. PET studies using [11C]XR9576 were performed in P-gp and/or Bcrp knockout mice as well as in wild-type mice. Metabolites of [11C]XR9576 were measured in the brain and plasma of mice. Results [11C]XR9576 was successfully synthesized with suitable radioactivity for injection as well as appropriate radiochemical purity and stability. In in vivo tissue distribution, the brain uptake of [11C]XR9576 significantly increased about tenfold of control on co-injection with >10 mg/kg of XR9576. In PET studies, the AUCbrain [0–60 min] in P-gp and P-gp/Bcrp knockout mice was 2- and 11-fold higher than that in wild-type mice. [11C]XR9576 showed a high metabolic stability (>90% unchanged form) in the brain and plasma of mice 30 min after injection. These results suggest that a tracer amount of [11C]XR9576 behave as the P-gp and Bcrp substrate, and the increased brain uptake or AUCbrain of [11C]XR9576 correlates with P-gp and Bcrp functions. Conclusions PET studies using [11C]XR9576 may be a promising approach for evaluating deficiency of the function of drug efflux transporters targeting intracranial diseases and tumors. |
|||||
| 書誌情報 |
Annals of Nuclear Medicine 巻 24, 号 5, p. 403-412, 発行日 2010-06 |
|||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0914-7187 | |||||
