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J Nucl Med. 2017 Apr;58(4):678-681. doi: 10.2967/jnumed.116.182147. Epub 2016 Oct 13.

Assessment of P-Glycoprotein Transport Activity at the Human Blood-Retina Barrier with (R)-11C-Verapamil PET.

Author information

1
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
2
Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
3
Imagerie Moléculaire In Vivo, IMIV, CEA, INSERM, CNRS, Université Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France.
4
Variabilité de Réponse aux Psychotropes, INSERM, U1144 and Faculté de Pharmacie, Université Paris Descartes, UMR-S 1144, Paris, France.
5
Department of Biomedical Imaging und Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
6
Department of Anesthesiology, General Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria; and.
7
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria oliver.langer@meduniwien.ac.at.
8
Health and Environment Department, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.

Abstract

P-glycoprotein (ABCB1) is expressed at the blood-retina barrier (BRB), where it may control distribution of drugs from blood to the retina and thereby influence drug efficacy and toxicity. Methods: We performed PET scans with the ABCB1 substrate (R)-11C-verapamil on 5 healthy male volunteers without and with concurrent infusion of the ABCB1 inhibitor tariquidar. We estimated the rate constants for radiotracer transfer across the BRB (K1, k2) and total retinal distribution volume VTResults: During ABCB1 inhibition, retinal VT and influx rate constant K1 were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant k2 was significantly decreased by 2.8 ± 1.0-fold. Conclusion: We found a significant increase in (R)-11C-verapamil distribution to the retina during ABCB1 inhibition, which provides first in vivo evidence for ABCB1 transport activity at the human BRB. The increase in retinal distribution was approximately 2.5-fold less pronounced than previously reported for the blood-brain barrier.

KEYWORDS:

P-glycoprotein; PET; blood–brain barrier; blood–retina barrier; eye

PMID:
27738009
DOI:
10.2967/jnumed.116.182147
[Indexed for MEDLINE]
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