Transporters involved in the hepatic uptake of 99mTc-mebrofenin and indocyanine green
Background & Aims:99mTc-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 of99mTc-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 and99mTc-mebrofenin are distinct. The aim of this study was to identify the specific human hepatic transporters of99mTc-mebrofenin and ICG. Methods: The uptake of99mTc-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 of99mTc-mebrofenin. OATP1B1 showed an approximately 1.5-fold higher affinity for99mTc-mebrofenin compared to OATP1B3. ICG is transported by OATP1B3 and NTCP. Conclusions: The transporter specificity of99mTc-mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3.99mTc- mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP.
- Liver disease
- Hepatobiliary scintigraphy
- Liver function test
- Na+-taurocholate co-transporting polypeptide
- Organic anion transporting polypeptide
- Transport kinetics