Hepatocyte transporters control the hepatobiliary elimination of many drugs, metabolites, and endogenous substances. Hepatocyte transporter function is altered in several pathophysiologic situations and can be modulated by certain drugs, with a potential impact for pharmacokinetics and drug-induced liver injury. The development of substrate probes with optimal properties for selective and quantitative imaging of hepatic transporters remains a challenge. 99mTc-mebrofenin has been used for decades for hepatobiliary scintigraphy, but the specific transporters controlling its liver kinetics have not been characterized until recently. These include sinusoidal influx transporters (organic anion-transporting polypeptides) responsible for hepatic uptake of 99mTc-mebrofenin, and efflux transporters (multidrug resistance-associated proteins) mediating its canalicular (liver-to-bile) and sinusoidal (liver-to-blood) excretion. Pharmacokinetic modeling enables molecular interpretation of 99mTc-mebrofenin scintigraphy data, thus offering a widely available translational method to investigate transporter-mediated drug-drug interactions in vivo. 99mTc-mebrofenin allows for phenotyping transporter function at the different poles of hepatocytes as a biomarker of liver function.
Keywords: ATP-binding cassette transporter; liver function; mebrofenin; pharmacokinetics; solute carrier transporter.
© 2021 by the Society of Nuclear Medicine and Molecular Imaging.