Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Laboratoire d'Imagerie Biomédicale Multimodale, BioMaps, Université Paris-Saclay, CEA, CNRS, INSERM, Service Hospitalier Frédéric Joliot, Orsay, France.
J Nucl Med. 2021 Aug 1;62(8):1043-1047. doi: 10.2967/jnumed.120.261321. Epub 2021 Mar 5.
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. Tc-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 Tc-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 Tc-mebrofenin scintigraphy data, thus offering a widely available translational method to investigate transporter-mediated drug-drug interactions in vivo. Tc-mebrofenin allows for phenotyping transporter function at the different poles of hepatocytes as a biomarker of liver function.
肝细胞转运体控制着许多药物、代谢物和内源性物质的肝胆排泄。在几种病理生理情况下，肝细胞转运体的功能会发生改变，某些药物也可以对其进行调节，从而对药代动力学和药物性肝损伤产生潜在影响。开发具有选择性和定量成像肝细胞转运体最佳特性的底物探针仍然是一个挑战。Tc-美罗芬宁已被用于肝胆闪烁成像数十年，但直到最近才对其控制肝脏动力学的特定转运体进行了表征。这些转运体包括负责 Tc-美罗芬宁肝摄取的窦状隙摄取转运体（有机阴离子转运多肽），以及介导其胆小管（肝到胆汁）和窦状隙（肝到血液）排泄的排出转运体（多药耐药相关蛋白）。药代动力学模型使 Tc-美罗芬宁闪烁成像数据的分子解释成为可能，从而提供了一种广泛可用的转化方法，可在体内研究转运体介导的药物相互作用。Tc-美罗芬宁可作为肝功能的生物标志物，对肝细胞的不同两极的转运体功能进行表型分析。
