title: Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography.
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 K corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.
authors: PET centre, Uppsala University Hospital, 751 85 Uppsala, Sweden.
authors: Mark
authors: M
authors: Lubberink
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D049268:Positron-Emission Tomography
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1