In vivo assessment of the vascular disrupting effect of M410 by DCE-MRI biomarker in a rabbit model of liver tumor

Oncol Rep. 2014 Aug;32(2):709-15. doi: 10.3892/or.2014.3230. Epub 2014 Jun 4.

Abstract

The present study aimed to prospectively monitor the vascular disrupting effect of M410 by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rabbits with VX2 liver tumors. Twenty-eight rabbits bearing VX2 tumors in the left lobe of the liver were established and randomly divided into treatment and control groups, intravenously injected with 25 mg/kg M410 or sterile saline, respectively. Conventional and DCE-MRI data were acquired on a 3.0-T MR unit at pretreatment, 4 h, 1, 4, 7 and 14 days post-treatment. Histopathological examinations [hematoxylin and eosin (H&E) and CD34 immunohistochemisty staining] were performed at each time point. The dynamic changes in tumor volume, kinetic DCE-MRI parameter [volume transfer constant (Ktrans)] and histological data were evaluated. Tumors grew slower in the M410 group 4-14 days following treatment, compared with rapidly growing tumors in the control group (P<0.05). At 4 h, 1 and 4 days, Ktrans significantly decreased in the M410 group compared with that in the control group (P<0.05). However, Ktrans values were similar in the two groups for the other time points studied. The changes in DCE-MRI parameters were consistent with the results obtained from H&E and CD34 staining of the tumor tissues. DCE-MRI parameter Ktrans may be used as a non-invasive imaging biomarker to monitor the dynamic histological changes in tumors following treatment with the vascular targeting agent M410.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / pharmacokinetics
  • Animals
  • Bibenzyls / administration & dosage*
  • Bibenzyls / chemical synthesis
  • Bibenzyls / pharmacokinetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / pathology*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Organophosphates / administration & dosage*
  • Organophosphates / chemical synthesis
  • Organophosphates / pharmacokinetics
  • Rabbits
  • Stilbenes / administration & dosage*
  • Stilbenes / chemical synthesis
  • Stilbenes / pharmacokinetics

Substances

  • 3,4',5-trimethoxylstilbene-3'-O-phosphate
  • Angiogenesis Inhibitors
  • Bibenzyls
  • Biomarkers, Tumor
  • Organophosphates
  • Stilbenes
  • combretastatin