Abstract
P-glycoprotein function is associated with a number of neurodegenerative and psychiatric diseases as well as with pharmacoresistance to for example antiepileptic drugs. The ability to measure P-gp function in vivo would allow for an increased understanding of the mechanisms of disease and treatment. This review assesses the various approaches to in vivo quantification of P-gp function using currently available P-gp tracers and PET in humans. First, the use of compartment models, and their interpretation in terms of P-gp function at the blood-brain barrier, is discussed. Then, the methods that have been used to quantify PET data of the P-gp tracers [11C]verapamil, [11C]N-desmetyl-loperamide (dLop), [11C]laniquidar, [11C]phenytoin, [11C]tariquidar and [11C]elacridar are reviewed. In summary, the extraction of P-gp substrate PET tracers, which is their plasma to tissue rate constant K1 corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.
Keywords: PET, P-glycoprotein, quantification, tracer kinetics, blood-brain barrier.
Current Pharmaceutical Design
Title:Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography
Volume: 22 Issue: 38
Author(s): Mark Lubberink
Affiliation:
Keywords: PET, P-glycoprotein, quantification, tracer kinetics, blood-brain barrier.
Abstract: P-glycoprotein function is associated with a number of neurodegenerative and psychiatric diseases as well as with pharmacoresistance to for example antiepileptic drugs. The ability to measure P-gp function in vivo would allow for an increased understanding of the mechanisms of disease and treatment. This review assesses the various approaches to in vivo quantification of P-gp function using currently available P-gp tracers and PET in humans. First, the use of compartment models, and their interpretation in terms of P-gp function at the blood-brain barrier, is discussed. Then, the methods that have been used to quantify PET data of the P-gp tracers [11C]verapamil, [11C]N-desmetyl-loperamide (dLop), [11C]laniquidar, [11C]phenytoin, [11C]tariquidar and [11C]elacridar are reviewed. In summary, the extraction of P-gp substrate PET tracers, which is their plasma to tissue rate constant K1 corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.
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Cite this article as:
Lubberink Mark, Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography, Current Pharmaceutical Design 2016; 22 (38) . https://dx.doi.org/10.2174/1381612822666160804093852
DOI https://dx.doi.org/10.2174/1381612822666160804093852 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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