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  • Meeting abstract
  • Open Access

P-Glycoprotein inhibition at the blood-brain barrier visualized with (R)-[11C]verapamil μPET

  • 1,
  • 5,
  • 1, 2,
  • 3,
  • 1,
  • 1,
  • 1,
  • 4,
  • 5,
  • 1,
  • 2 and
  • 1, 2Email author
BMC Pharmacology20077 (Suppl 2) :A24

https://doi.org/10.1186/1471-2210-7-S2-A24

  • Published:

Keywords

  • Blood Sampling
  • Positron Emission Tomography
  • Verapamil
  • Plasma Protein
  • Anticancer Drug

Introduction

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).

Methods

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.

Results

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.

Conclusion

Our pilot data suggest that VPM PET is a sensitive tool to quantitatively visualize P-gp inhibition at the animal and human BBB.

Authors’ Affiliations

(1)
Department of Radiopharmaceuticals, ARC GmbH, Seibersdorf, Austria
(2)
Department of Clinical Pharmacology, Medical University of Vienna, Austria
(3)
Department of Medical Computer Sciences, Medical University of Vienna, Austria
(4)
Department of Nuclear Medicine, Medical University of Vienna, Austria
(5)
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine Hannover, Germany

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