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

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 [C-11] verapamil, [C-11] N-desmetyl-loperamide (dLop), [C-11] laniquidar, [C-11] phenytoin, [C-11] tariquidar and [C-11] elacridar are reviewed. In summary, the extraction of P-gp substrate PET tracers, which is their plasma to tissue rate constant K-1 corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.