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

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

Research output: Contribution to journalArticleAcademicpeer-review

192 Citations (Scopus)

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 1CG. 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. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)738-745
Number of pages8
JournalJournal of Hepatology
Volume54
Issue number4
DOIs
Publication statusPublished - 2011

Cite this