RT Journal Article SR Electronic T1 Tariquidar-Induced P-Glycoprotein Inhibition at the Rat Blood–Brain Barrier Studied with (R)-11C-Verapamil and PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1328 OP 1335 DO 10.2967/jnumed.108.051235 VO 49 IS 8 A1 Jens P. Bankstahl A1 Claudia Kuntner A1 Aiman Abrahim A1 Rudolf Karch A1 Johann Stanek A1 Thomas Wanek A1 Wolfgang Wadsak A1 Kurt Kletter A1 Markus Müller A1 Wolfgang Löscher A1 Oliver Langer YR 2008 UL http://jnm.snmjournals.org/content/49/8/1328.abstract AB The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood–brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. Methods: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). Results: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 ± 0.81 vs. 0.30 ± 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose–response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 ± 9.5 mg/kg. Conclusion: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.