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

Autor: Michal Heger, Bruno Stieger, Gert van Cappellen, Gerd A. Kullak-Ublick, Stephanie Häusler, Rolf Hesselmann, Thomas M. van Gulik, Tessa M van Ginhoven, Wilmar de Graaf, Roelof J. Bennink
Přispěvatelé: Surgery, Developmental Biology, University of Zurich, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, AII - Amsterdam institute for Infection and Immunity, Nuclear Medicine
Rok vydání: 2011
Předmět:
Organic anion transporter 1
genetic structures
Organic Anion Transporters
Pharmacology
Organic Anion Transporters
Sodium-Independent

chemistry.chemical_compound
Xenopus laevis
0302 clinical medicine
Liver Function Tests
Cricetinae
0303 health sciences
Aniline Compounds
Microscopy
Confocal

biology
medicine.diagnostic_test
Symporters
Chemistry
Liver-Specific Organic Anion Transporter 1
Chinese hamster ovary cell
Organotechnetium Compounds
Recombinant Proteins
3. Good health
Organic anion-transporting polypeptide
Liver
030220 oncology & carcinogenesis
Female
Indocyanine Green
medicine.medical_specialty
Bilirubin
Glycine
Organic Anion Transporters
Sodium-Dependent

610 Medicine & health
CHO Cells
In Vitro Techniques
Transfection
03 medical and health sciences
Solute Carrier Organic Anion Transporter Family Member 1B3
Cricetulus
Internal medicine
medicine
Animals
Humans
Radionuclide Imaging
030304 developmental biology
Hepatology
Imino Acids
Transporter
eye diseases
Endocrinology
10199 Clinic for Clinical Pharmacology and Toxicology
biology.protein
Oocytes
2721 Hepatology
Liver function
Radiopharmaceuticals
Liver function tests
Indocyanine green
Zdroj: Journal of hepatology
Journal of Hepatology, 54(4), 738-745. Elsevier
Journal of hepatology, 54(4), 738-745. Elsevier
ISSN: 0168-8278
Popis: 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.
Databáze: OpenAIRE