The purpose of this study was to determine whether the brain uptake of [18 F]FPEB is influenced by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) as efflux transporters in rodents. To assess this possible modulation, positron emission tomography studies were performed in animal models of pharmacological or genetic ablation of these transporters. Compared with the control conditions, when P-gp was blocked with tariquidar, there was an 8%-12% increase in the brain uptake of [18 F]FPEB. In P-gp knockout mice, such as Mdr1a/b(-/-) and Mdr1a/b(-/-) Bcrp1(-/-) , genetic ablation models, there was an increment of 8%-53% in [18 F]FPEB uptake compared with that in the wild-type mice. In contrast, Bcrp knockout mice showed a decrement of 5%-12% uptake and P-gp/Bcrp knockout group displayed an increment of 5%-17% compared with wild type. These results indicate that [18 F]FPEB is possibly a weak substrate for P-gp.

中文翻译：

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P-gp和Bcrp作为脑外排转运蛋白对鼠脑中[18 F] FPEB摄取的影响。

这项研究的目的是确定[18 F] FPEB的大脑摄取是否受到P-糖蛋白（P-gp）和乳腺癌抗性蛋白（Bcrp）作为啮齿动物外排转运蛋白的影响。为了评估这种可能的调节，在这些转运蛋白的药理或遗传消融的动物模型中进行了正电子发射断层扫描研究。与对照条件相比，当用tariquidar阻断P-gp时，[18 F] FPEB的大脑摄取增加了8％-12％。在P-gp基因敲除小鼠中，例如Mdr1a / b（-/-）和Mdr1a / b（-/-）Bcrp1（-/-）遗传消融模型，在[18]中增加了8％-53％与野生型小鼠相比，F] FPEB的摄取。相反，与野生型相比，Bcrp基因敲除小鼠的摄取减少了5％-12％，P-gp / Bcrp基因敲除组的摄取增加了5％-17％。