采用 [(11)C]GF120918 通过 PET 评估与 P-糖蛋白和乳腺癌耐药蛋白相关的脑穿透限制在小鼠中的作用。
Evaluation of limiting brain penetration related to P-glycoprotein and breast cancer resistance protein using [(11)C]GF120918 by PET in mice.
机构信息
Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
出版信息
Mol Imaging Biol. 2011 Feb;13(1):152-60. doi: 10.1007/s11307-010-0313-1.
PURPOSE
GF120918 has a high inhibitory effect on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). We developed [(11)C]GF120918 as a positron emission tomography (PET) probe to assess if dual modulation of P-gp and BCRP is useful to evaluate brain penetration.
PROCEDURES
PET studies using [(11)C]GF120918 were conducted on P-gp and/or Bcrp knockout mice as well as wild-type mice.
RESULTS
In PET studies, the AUC(brain) ([0-60 min]) and K (1) value in P-gp/Bcrp knockout mice were nine- and 26-fold higher than that in wild-type mice, respectively. These results suggest that brain penetration of [(11)C]GF120918 is related to modulation of P-gp and BCRP and is limited by two transporters working together.
CONCLUSIONS
PET using [(11)C]GF120918 may be useful for evaluating the function of P-gp and BCRP. PET using P-gp/Bcrp knockout mice may be an effective method to understand the overall contributions the functions of P-gp and BCRP.
目的
GF120918 对 P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）具有很强的抑制作用。我们开发了 [(11)C]GF120918 作为正电子发射断层扫描（PET）探针，以评估双重调节 P-gp 和 BCRP 是否有助于评估脑穿透。
方法
在 P-gp 和/或 Bcrp 敲除小鼠以及野生型小鼠中进行了使用 [(11)C]GF120918 的 PET 研究。
结果
在 PET 研究中，P-gp/Bcrp 敲除小鼠的脑区（[0-60 分钟]）AUC 和 K (1) 值分别比野生型小鼠高 9 倍和 26 倍。这些结果表明，[(11)C]GF120918 的脑穿透与 P-gp 和 BCRP 的调节有关，并且受到两种协同作用的转运体的限制。
结论
使用 [(11)C]GF120918 的 PET 可能有助于评估 P-gp 和 BCRP 的功能。使用 P-gp/Bcrp 敲除小鼠的 PET 可能是一种有效的方法，可以了解 P-gp 和 BCRP 功能的整体贡献。
Zotero 插件