PT - JOURNAL ARTICLE AU - Solène Marie AU - Irene Hernández-Lozano AU - Oliver Langer AU - Nicolas Tournier TI - Repurposing <sup>99m</sup>Tc-Mebrofenin as a Probe for Molecular Imaging of Hepatocyte Transporters AID - 10.2967/jnumed.120.261321 DP - 2021 Aug 01 TA - Journal of Nuclear Medicine PG - 1043--1047 VI - 62 IP - 8 4099 - http://jnm.snmjournals.org/content/62/8/1043.short 4100 - http://jnm.snmjournals.org/content/62/8/1043.full SO - J Nucl Med2021 Aug 01; 62 AB - 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.