Dose-response assessment of tariquidar for inhibition of P-glycoprotein at the human blood-brain barrier using (R)-[11C]verapamil PET

Background Positron emission tomography (PET) with the radiolabelled substrate of the multidrug efflux transporter Pglycoprotein (P-gp) (R)-[C]verapamil (VPM) can be used to assess P-gp function at the blood-brain barrier (BBB). We have shown in rats that performing VPM PET scans after half-maximum inhibition of P-gp with the third-generation P-gp inhibitor tariquidar (TQD) is more sensitive for detecting regional differences in cerebral P-gp function than VPM baseline scans [1]. In order to translate this concept to humans a detailed understanding of the dose-response relationship of TQD for inhibition of P-gp at the human BBB is required.