P-Glycoprotein inhibition at the blood-brain barrier visualized with (R)-[11C]verapamil μPET
© Kuntner et al; licensee BioMed Central Ltd. 2007
Published: 14 November 2007
Inhibition of the multidrug efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) is considered a promising strategy in order to increase intracerebral penetration of therapeutics, such as antiepileptic and anticancer drugs. The aim of this study was to evaluate the usefulness of (R)-[11C]verapamil (VPM) and small-animal positron emission tomography (μPET) to measure P-gp inhibition at the BBB following administration of the third-generation P-gp inhibitor tariquidar (TQD, Xenova, UK).
Five Wistar Unilever rats underwent paired VPM μPET scans, one baseline scan followed by i.v. administration of TQD (15 mg/kg) and a second PET scan at 2 hour after TQD administration. Arterial blood sampling was performed along with analysis of metabolism and plasma protein binding of VPM.
Following TQD administration, the brain-to-plasma ratio of radioactivity was increased by a factor of 11–16 as compared to baseline scans, whereas VPM metabolism and plasma protein binding were left unaffected.
Our pilot data suggest that VPM PET is a sensitive tool to quantitatively visualize P-gp inhibition at the animal and human BBB.
This article is published under license to BioMed Central Ltd.