TY - JOUR T1 - In Vivo Evaluation of P-glycoprotein Function at the Blood-Brain Barrier in Nonhuman Primates Using [<sup>11</sup>C]Verapamil JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 647 LP - 653 DO - 10.1124/jpet.105.088328 VL - 316 IS - 2 AU - Young-Joo Lee AU - Jun Maeda AU - Hiroyuki Kusuhara AU - Takashi Okauchi AU - Motoki Inaji AU - Yuji Nagai AU - Shigeru Obayashi AU - Ryuji Nakao AU - Kazutoshi Suzuki AU - Yuichi Sugiyama AU - Tetsuya Suhara Y1 - 2006/02/01 UR - http://jpet.aspetjournals.org/content/316/2/647.abstract N2 - P-glycoprotein (P-gp) is a major efflux transporter contributing to the efflux of a range of xenobiotic compounds at the blood-brain barrier (BBB). In the present study, we evaluated the P-gp function at the BBB using positron emission tomography (PET) in nonhuman primates. Serial brain PET scans were obtained in three rhesus monkeys after intravenous administration of [11C]verapamil under control and P-gp inhibition conditions ([PSC833 ([3′-keto-Me-Bmt1]-[Val2]-cyclosporin) 20 mg/kg/2 h]). The parent [11C]verapamil and its metabolites in plasma were determined by HPLC with a positron detector. The initial brain uptake clearance calculated from the integration plot was used for the quantitative analysis. After intravenous administration, [11C]verapamil was taken up rapidly into the brain (time to reach the peak, 0.58 min). The blood level of [11C]verapamil decreased rapidly, and it underwent metabolism with time. The inhibition of P-gp by PSC833 increased the brain uptake of [11C]verapamil 4.61-fold (0.141 versus 0.651 ml/g brain/min, p &lt; 0.05). These results suggest that PET measurement with [11C]verapamil can be used for the evaluation of P-gp function at the BBB in the living brain. The American Society for Pharmacology and Experimental Therapeutics ER -