Effects of P‐gp and Bcrp as brain efflux transporters on the uptake of [18F]FPEB in the murine brain

The purpose of this study was to determine whether the brain uptake of [18F]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 [18F]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 [18F]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 [18F]FPEB is possibly a weak substrate for P‐gp. [18F]FPEB is a radiotracer for mGluR5. Pharmacological and genetic inhibition of efflux transporters in the blood–brain barrier demonstrated that it is a weak substrate P‐gp in the rodent.