P-Glycoprotein, not BCRP, Limits the Brain Uptake of [F-18]Mefway in Rodent Brain

Abstract

Purpose The aim of this study was to determine whether the brain uptake of [F-18]Mefway is influenced by the action of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) in rodents. Procedures: [F-18]Mefway was applied to rats pharmacologically inhibited with tariquidar (TQD) and to genetically disrupted mice. Results: Pretreatment of TQD results in 160 % higher hippocampal uptake compared with control rats. In genetically disrupted mice, a maximal brain uptake value of 3.2 SUV in the triple knockout mice (tKO, Mdr1a/b((-/-))Bcrp1((-/-))) was comparable to that of the double knockout mice (dKO, Mdr1a/b((-/-))) and 2-fold those of the wild-type and Bcrp1((-/-)) knockout mice. The differences of binding values were statistically insignificant between control and experimental groups. The brain-to-plasma ratios for tKO mice were also two to five times higher than those for other groups. Conclusions: [F-18]Mefway is modulated by P-gp, and not by Bcrp in rodents.