Importance of P-gp PET Imaging in Pharmacology

Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which works as a functional blood-brain barrier (BBB). P-gp pumps out multiple types of molecules from the brain parenchyma into the blood. Therefore, altered P-gp function at the BBB will change the concentrations of therapeutic drugs in the central nervous system (CNS) and hence impact the toxicity and efficacy of CNS drugs. Positron emission tomography (PET) is the only way to non-invasively measure P-gp function in the living human brain. PET imaging of P-gp function was first demonstrated in 1998 with the substrate tracer racemic [11C]verapamil. Since then, several drug interaction studies and proof-of-concept studies regarding drug resistance have been performed with P-gp PET imaging. Although preclinical findings have been very positive regarding the possibilities and importance of P-gp PET imaging, very few studies have shown the clinical relevance of P-gp PET imaging in different disorders of the brain. This review summarizes the pharmacological studies with PET using substrate tracers and emphasizes the importance of PET imaging to understand the mechanism of action of CNS drugs.