@article{oai:repo.qst.go.jp:00046121,
 author = {Yamasaki, Tomoteru and Fujinaga, Masayuki and Kawamura, Kazunori and Hatori, Akiko and Yui, Joji and Nengaki, Nobuki and Ogawa, Masanao and Yoshida, Yuichiro and Wakizaka, Hidekatsu and Yanamoto, Kazuhiko and Fukumura, Toshimitsu and Zhang, Ming-Rong and 山崎 友照 and 藤永 雅之 and 河村 和紀 and 羽鳥 晶子 and 由井 譲二 and 念垣 信樹 and 小川 政直 and 吉田 勇一郎 and 脇坂 秀克 and 柳本 和彦 and 福村 利光 and 張 明栄},
 issue = {5},
 journal = {Nuclear Medicine and Biology},
 month = {Jul},
 note = {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.},
 pages = {707--714},
 title = {Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated brain penetration of 11C-labeled topotecan using small-animal positron emission tomography},
 volume = {38},
 year = {2011}
}