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PET Tracers To Study Clinically Relevant Hepatic Transporters.

Transporter proteins expressed on the cell membranes of hepatocytes are directly involved in the hepatic clearance, mediating the transport of drugs and metabolites through the hepatocyte, from the bloodstream into the bile. Reduction of hepatic transporter activity (due to chemical inhibition, genetic polymorphism, or low expression) can increase systemic or liver exposure to potentially toxic compounds, causing adverse effects. Many clinically used drugs have been associated with inhibition of hepatic transporters in vitro, suggesting the potential involvement of liver transporters in drug-drug interactions (DDIs). Recently, radiolabeled hepatic transporter substrates have been successfully employed in positron emission tomography (PET) imaging to demonstrate inhibition of clinically relevant hepatic transporters. The present article briefly describes the clinical relevance of hepatic transporters followed by a review of the application of PET imaging for the determination of pharmacokinetic parameters useful to describe the transporter activity and the design, accessibility, and preclinical and clinical applications of available radiotracers. Finally, based on the analysis of the strengths and limitations of the available tracers, some criteria for the development of novel PET probes for hepatic transporters and new potential applications are suggested.