RT Journal Article SR Electronic T1 Repurposing 99mTc-Mebrofenin as a Probe for Molecular Imaging of Hepatocyte Transporters JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1043 OP 1047 DO 10.2967/jnumed.120.261321 VO 62 IS 8 A1 Solène Marie A1 Irene Hernández-Lozano A1 Oliver Langer A1 Nicolas Tournier YR 2021 UL http://jnm.snmjournals.org/content/62/8/1043.abstract 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.