Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography

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.

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