Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green.

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de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, Kullak-Ublick GA, Hesselmann R, van Gulik TM, Stieger B

Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green.

J Hepatol. 2011 Apr;54(4):738-45. doi: 10.1016/j.jhep.2010.07.047. Epub 2010 Oct 1.

PubMed ID

21163547 [ View in PubMed

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Abstract

BACKGROUND & AIMS: (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) and the indocyanine green (ICG) clearance test are used for the assessment of hepatic function before and after liver surgery. The hepatic uptake of (99m)Tc-mebrofenin and ICG is considered similar to the uptake of organic anions such as bilirubin and bile acids. Little is known about hepatic uptake mechanisms of both compounds and recent evidence suggests that the hepatic transporters for ICG and (99m)Tc-mebrofenin are distinct. The aim of this study was to identify the specific human hepatic transporters of (99m)Tc-mebrofenin and ICG. METHODS: The uptake of (99m)Tc-mebrofenin was investigated in cRNA-injected Xenopus laevis oocytes expressing human OATP1B1, OATP1B3, OATP2B1, or NTCP. Chinese hamster ovary (CHO) cells stably expressing OATP1B1, OATP1B3, OATP2B1, or NTCP were used as a mammalian expression system. ICG transport into CHO cells was additionally imaged with confocal microscopy. RESULTS: We demonstrated that OATP1B1 and OATP1B3 are involved in the transport of (99m)Tc-mebrofenin. OATP1B1 showed an approximately 1.5-fold higher affinity for (99m)Tc-mebrofenin compared to OATP1B3. ICG is transported by OATP1B3 and NTCP. CONCLUSIONS: The transporter specificity of (99m)Tc-mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3. (99m)Tc-mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP.

DrugBank Data that Cites this Article

Drugs

Technetium Tc-99m mebrofenin

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Technetium Tc-99m mebrofenin	Solute carrier organic anion transporter family member 1B1	Protein	Humans	No	Substrate	Details
Technetium Tc-99m mebrofenin	Solute carrier organic anion transporter family member 1B3	Protein	Humans	No	Substrate	Details