Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is an MRI contrast agent with perfusion and hepatoselective properties. The purpose of the study was to examine uptake of Gd-EOB-DTPA in the hepatobiliary phase in hepatocellular carcinoma (HCC).
A retrospective analysis of 22 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI was performed. Enhancement ratios (ERs) and expression levels of the organic anion transporter (OATP) 1B3 protein were examined.
Gd-EOB-DTPA accumulated in the hepatobiliary phase in 6 of the 22 cases. All 6 Gd-EOB-DTPA-positive cases were moderately differentiated HCC, but 11 other moderately differentiated HCCs did not show Gd-EOB-DTPA uptake. Histopathologically, 4 Gd-EOB-DTPA-positive HCCs and 5 Gd-EOB-DTPA-negative HCCs produced bile. HCCs with Gd-EOB-DTPA uptake overexpressed OATP1B3 compared with HCCs without Gd-EOB-DTPA uptake, and OATP1B3 levels were significantly correlated with ERs (r = 0.91, P < 0.0001).
Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than by tumor differentiation or bile production.
- Semelka, RC, Helmberger, TK (2001) Contrast agents for MR imaging of the liver. Radiology 218: pp. 27-38
- Hamm, B, Staks, T, Muhler, A, Bollow, M, Taupitz, M, Frenzel, T (1995) Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology 195: pp. 785-792
- Vogl, TJ, Kummel, S, Hammerstingl, R, Schellenbeck, M, Schumacher, G, Balzer, T (1996) Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology 200: pp. 59-67
- Reimer, P, Rummeny, EJ, Shamsi, K, Balzer, T, Daldrup, HE, Tombach, B (1996) Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. Radiology 199: pp. 177-183
- Zech, CJ, Herrmann, KA, Reiser, MF, Schoenberg, SO (2007) MR imaging in patients with suspected liver metastases: value of liver-specific contrast agent Gd-EOB-DTPA. Magn Reson Med Sci 6: pp. 43-52 CrossRef
- Ichikawa, T (2004) MRI in the evaluation of hepatocellular nodules: role of pulse sequences and contrast agents. Intervirology 47: pp. 252-270 CrossRef
- Huppertz, A, Haraida, S, Kraus, A, Zech, CJ, Scheidler, J, Breuer, J (2005) Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT—initial observations. Radiology 234: pp. 468-478 CrossRef
- Saito, K, Kotake, F, Ito, N, Ozuki, T, Mikami, R, Abe, K (2005) Gd-EOB-DTPA enhanced MRI for hepatocellular carcinoma: quantitative evaluation of tumor enhancement in hepatobiliary phase. Magn Reson Med Sci 4: pp. 1-9 CrossRef
- Scheuer PJ, Lefkowitch JH. Liver biopsy interpretation. 7th edn. Philadelphia: WB Saunders; 2006.
- Fujita, M, Yamamoto, R, Takahashi, M, Tsuji, T, Yamanaka, T, Miyazawa, T (1997) Paradoxic uptake of Gd-EOB-DTPA by hepatocellular carcinoma in mice: quantitative image analysis. J Magn Reson Imaging 7: pp. 768-770 CrossRef
- Ni, Y, Marchal, G, Yu, J, Muhler, A, Lukito, G, Baert, AL (1994) Prolonged positive contrast enhancement with Gd-EOB-DTPA in experimental liver tumors: potential value in tissue characterization. J Magn Reson Imaging 4: pp. 355-363 CrossRef
- Konig, J, Seithel, A, Gradhand, U, Fromm, MF (2006) Pharmacogenomics of human OATP transporters. Naunyn Schmiedebergs Arch Pharmacol 372: pp. 432-443 CrossRef
- Montfoort, JE, Stieger, B, Meijer, DK, Weinmann, HJ, Meier, PJ, Fattinger, KE (1999) Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1. J Pharmacol Exp Ther 290: pp. 153-157
- Libra, A, Fernetti, C, Lorusso, V, Visigalli, M, Anelli, PL, Staud, F (2006) Molecular determinants in the transport of a bile acid-derived diagnostic agent in tumoral and nontumoral cell lines of human liver. J Pharmacol Exp Ther 319: pp. 809-817 CrossRef
- Pascolo, L, Petrovic, S, Cupelli, F, Bruschi, CV, Anelli, PL, Lorusso, V (2001) Abc protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles. Biochem Biophys Res Commun 282: pp. 60-66 CrossRef
- Borst, P, Elferink, RO (2002) Mammalian ABC transporters in health and disease. Annu Rev Biochem 71: pp. 537-592 CrossRef
- Abe, T, Unno, M, Onogawa, T, Tokui, T, Kondo, TN, Nakagomi, R (2001) LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology 120: pp. 1689-1699 CrossRef
- Smith, NF, Acharya, MR, Desai, N, Figg, WD, Sparreboom, A (2005) Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel. Cancer Biol Ther 4: pp. 815-818 CrossRef
- Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma
Journal of Gastroenterology
Volume 44, Issue 7 , pp 793-798
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Green hepatoma
- Industry Sectors
- Author Affiliations
- 1. Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
- 2. Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- 3. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan