title: Effect of change in transporter expression on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging during hepatocarcinogenesis in rats.
abstract: OBJECTIVE
  To analyze the difference in signal intensity on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) among various hepatocellular nodules during hepatocarcinogenesis as correlated with the expressions of the transporters of Gd-EOB-DTPA.
  
  
  METHODS
  We received institutional animal review board approval prior to the commencement of all studies. Forty rats were divided into three groups. The rats in the tumor groups received N-nitrosomorpholine solution (n = 16), and rats in the cirrhosis group (thioacetamide [TAA] group) received thioacetamide solution (n = 12). As a control, the remaining 12 rats were fed normal water. Each group was divided into two sub-groups: Group 1 for Gd-EOB-DTPA-enhanced MRI (0.025 mmol Gd/kg, n =7) and Group 2 for reverse transcription-polymerase chain reaction to compare transporter (oatp1 and mrp2) expressions (n = 5 for control and TAA groups, n = 9 for tumor groups).
  
  
  RESULTS
  Signal enhancement of tumors decreased according to the progress of hepatocarcinogenesis. Although the relative enhancement of each tumor group was significantly lower than that of the control group (P < 0.01), and there was no significant difference between TAA, hyperplastic nodules (HPN), and HCC(well) groups. The relative enhancement of the HCC(mod) group was significantly lower than the other groups (P < 0.01). The oatp1 expression of HPN tended to be higher than those of HCC(well) and HCC(mod). The mrp2 expression of TAA was significantly higher than those of HCC(well), HCC(mod), HPN and control (P < 0.01). The mrp2 expression of HPN tended to be higher than those of HCC(well ) and HCC(mod).
  
  
  CONCLUSIONS
  It was suggested that the signal enhancement on Gd-EOB-DTPA-enhanced MRI would correlate with the transporter expression in various hepatocellular nodules during hepatocarcinogenesis.
authors.affiliation: Diagnostic Imaging Medical Affair, Medical Affairs, Bayer Yakuhin, Ltd., Osaka, Japan. natsuko.tsuda@bayerhealthcare.com
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tsuda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000378:metabolism; D018450:Disease Progression; D019786:Gadolinium DTPA / Q000378:metabolism; D006965:Hyperplasia; D007834:Lasers; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D042282:Microdissection / Q000295:instrumentation; D009602:Nitrosamines; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide; D013997:Time Factors
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D003287:Contrast Media; D009602:Nitrosamines; D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; C073590:gadolinium ethoxybenzyl DTPA; D013853:Thioacetamide; C002741:N-nitrosomorpholine; D019786:Gadolinium DTPA