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Expert Opin Drug Metab Toxicol. 2020 Feb;16(2):149-164. doi: 10.1080/17425255.2020.1718107. Epub 2020 Jan 23.

Use of imaging to assess the activity of hepatic transporters.

Author information

1
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
2
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
3
Preclinical Molecular Imaging, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.

Abstract

Introduction: Membrane transporters of the SLC and ABC families are abundantly expressed in the liver, where they control the transfer of drugs/drug metabolites across the sinusoidal and canalicular hepatocyte membranes and play a pivotal role in hepatic drug clearance. Noninvasive imaging methods, such as PET, SPECT or MRI, allow for measuring the activity of hepatic transporters in vivo, provided that suitable transporter imaging probes are available.Areas covered: We give an overview of the working principles of imaging-based assessment of hepatic transporter activity. We discuss different currently available PET/SPECT radiotracers and MRI contrast agents and their applications to measure hepatic transporter activity in health and disease. We cover mathematical modeling approaches to obtain quantitative parameters of transporter activity and provide a critical assessment of methodological limitations and challenges associated with this approach.Expert opinion: PET in combination with pharmacokinetic modeling can be potentially applied in drug development to study the distribution of new drug candidates to the liver and their clearance mechanisms. This approach bears potential to mechanistically assess transporter-mediated drug-drug interactions, to assess the influence of disease on hepatic drug disposition and to validate and refine currently available in vitro-in vivo extrapolation methods to predict hepatic clearance of drugs.

KEYWORDS:

Hepatic clearance; PET imaging; liver; pharmacokinetics; transporters

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