Department of Experimental Surgery, Academic Medical Center, Amsterdam, The Netherlands.
J Hepatol. 2011 Apr;54(4):738-45. doi: 10.1016/j.jhep.2010.07.047. Epub 2010 Oct 1.
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.
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.
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.
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.
（99m）Tc-美罗芬宁肝胆闪烁显像（HBS）和吲哚菁绿（ICG）清除试验用于评估肝手术前后的肝功能。（99m）Tc-美罗芬宁和 ICG 的肝脏摄取被认为类似于胆红素和胆汁酸等有机阴离子的摄取。关于这两种化合物的肝脏摄取机制知之甚少，最近的证据表明，ICG 和（99m）Tc-美罗芬宁的肝脏转运体是不同的。本研究旨在确定（99m）Tc-美罗芬宁和 ICG 的特定人类肝脏转运体。
在表达人 OATP1B1、OATP1B3、OATP2B1 或 NTCP 的 cRNA 注射非洲爪蟾卵母细胞中研究（99m）Tc-美罗芬宁的摄取。使用稳定表达 OATP1B1、OATP1B3、OATP2B1 或 NTCP 的中国仓鼠卵巢（CHO）细胞作为哺乳动物表达系统。还使用共聚焦显微镜对 ICG 转运到 CHO 细胞进行了成像。
我们证明 OATP1B1 和 OATP1B3 参与（99m）Tc-美罗芬宁的转运。OATP1B1 对（99m）Tc-美罗芬宁的亲和力约比 OATP1B3 高 1.5 倍。ICG 由 OATP1B3 和 NTCP 转运。
（99m）Tc-美罗芬宁和 ICG 的转运体特异性部分重叠，因为这两种化合物均由 OATP1B3 转运。（99m）Tc-美罗芬宁也被 OATP1B1 摄取，而 ICG 还被 NTCP 转运。
