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Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated brain penetration of 11C-labeled topotecan using small-animal positron emission tomography
https://repo.qst.go.jp/records/46121
https://repo.qst.go.jp/records/46121d75be7be-7b49-4bd7-8f56-cb11c87b68c6
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-07-04 | |||||
| タイトル | ||||||
| タイトル | Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated brain penetration of 11C-labeled topotecan using small-animal positron emission tomography | |||||
| 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 |
Yamasaki, Tomoteru
× Yamasaki, Tomoteru× Fujinaga, Masayuki× Kawamura, Kazunori× Hatori, Akiko× Yui, Joji× Nengaki, Nobuki× Ogawa, Masanao× Yoshida, Yuichiro× Wakizaka, Hidekatsu× Yanamoto, Kazuhiko× Fukumura, Toshimitsu× Zhang, Ming-Rong× 山崎 友照× 藤永 雅之× 河村 和紀× 羽鳥 晶子× 由井 譲二× 念垣 信樹× 小川 政直× 吉田 勇一郎× 脇坂 秀克× 柳本 和彦× 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 | Introduction: Topotecan (TPT) is a camptothecin derivative and is an anticancer drug working as a topoisomerase-I-specific inhibitor.But TPT cannot penetrate through the blood–brain barrier. In this study, we synthesized a new positron emission tomography (PET)probe, [11C]TPT, to evaluate the P-glycoprotein (Pgp)- and breast cancer resistance protein (BCRP)-mediated brain penetration of [11C] TPT using small-animal PET. Methods: [11C]TPT was synthesized by the reaction of a desmethyl precursor with [11C]CH3I. In vitro study using [11C]TPT was carried out in MES-SA and doxorubicin-resistant MES-SA/Dx5 cells in the presence or absence of elacridar, a specific inhibitor for Pgp and BCRP. The biodistribution of [11C]TPT was determined using small-animal PET and the dissection method in mice. Results: The transport of [11C]TPT to the extracellular side was determined in MES-SA/Dx5 cells exhibiting the expressions of Pgp and BCRP at high levels. This transport was inhibited by coincubation with elacridar. In Mdr1a/b−/−Bcrp1−/− mice, PET results indicated that the brain uptake of [11C]TPT was about two times higher than that in wild-type mice. Similarly, the brain penetration of [11C]TPT in wild-type mice was increased by treatment with elacridar. The radioactivity in the brain of elacridar-treated mice was maintained at a certain level after the injection of [11C]TPT, although the radioactivity in the blood decreased with time. Conclusions: We demonstrated the increase of brain penetration of [11C]TPT by deficiency and inhibition of Pgp and BCRP functions using small-animal PET in mice. |
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| 書誌情報 |
Nuclear Medicine and Biology 巻 38, 号 5, p. 707-714, 発行日 2011-07 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
