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Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green.
- Source :
-
Journal of hepatology [J Hepatol] 2011 Apr; Vol. 54 (4), pp. 738-45. Date of Electronic Publication: 2010 Oct 01. - Publication Year :
- 2011
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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.<br />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.<br />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.<br />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.<br /> (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Aniline Compounds
Animals
CHO Cells
Cricetinae
Cricetulus
Female
Glycine
Humans
In Vitro Techniques
Liver diagnostic imaging
Liver metabolism
Liver Function Tests
Liver-Specific Organic Anion Transporter 1
Microscopy, Confocal
Oocytes metabolism
Organic Anion Transporters genetics
Organic Anion Transporters, Sodium-Dependent genetics
Organic Anion Transporters, Sodium-Dependent metabolism
Organic Anion Transporters, Sodium-Independent genetics
Organic Anion Transporters, Sodium-Independent metabolism
Radionuclide Imaging
Radiopharmaceuticals pharmacokinetics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Solute Carrier Organic Anion Transporter Family Member 1B3
Symporters genetics
Symporters metabolism
Transfection
Xenopus laevis
Imino Acids pharmacokinetics
Indocyanine Green pharmacokinetics
Organic Anion Transporters metabolism
Organotechnetium Compounds pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 54
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 21163547
- Full Text :
- https://doi.org/10.1016/j.jhep.2010.07.047