PT  - JOURNAL ARTICLE
AU  - Jens P. Bankstahl
AU  - Claudia Kuntner
AU  - Aiman Abrahim
AU  - Rudolf Karch
AU  - Johann Stanek
AU  - Thomas Wanek
AU  - Wolfgang Wadsak
AU  - Kurt Kletter
AU  - Markus Müller
AU  - Wolfgang Löscher
AU  - Oliver Langer
TI  - Tariquidar-Induced P-Glycoprotein Inhibition at the Rat Blood–Brain Barrier Studied with (<em>R</em>)-<sup>11</sup>C-Verapamil and PET
AID  - 10.2967/jnumed.108.051235
DP  - 2008 Aug 01
TA  - Journal of Nuclear Medicine
PG  - 1328--1335
VI  - 49
IP  - 8
4099  - http://jnm.snmjournals.org/content/49/8/1328.short
4100  - http://jnm.snmjournals.org/content/49/8/1328.full
SO  - J Nucl Med2008 Aug 01; 49
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.