Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma.
BACKGROUND
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than by tumor differentiation or bile production.
Narita
Masato
M
Department of Surgery, Graduate School of Medicine, Kyoto University, and Department of Diagnostic Pathology, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Hatano
Etsuro
E
Arizono
Shigeki
S
Miyagawa-Hayashino
Aya
A
Isoda
Hiroyoshi
H
Kitamura
Koji
K
Taura
Kojiro
K
Yasuchika
Kentaro
K
Nitta
Takashi
T
Ikai
Iwao
I
Uemoto
Shinji
S
D001646:Bile / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism*; D003287:Contrast Media / Q000378:metabolism; D005260:Female; D019786:Gadolinium DTPA / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D012189:Retrospective Studies; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
D003287:Contrast Media; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA