Low-molecular contrast agent dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted (DW)-MRI in early assessment of bevacizumab treatment in breast cancer xenografts

J Magn Reson Imaging. 2013 Nov;38(5):1043-53. doi: 10.1002/jmri.24079. Epub 2013 Mar 21.

Abstract

Purpose: To investigate the effect of bevacizumab treatment on vascular architecture and function in two xenograft models with different angiogenic properties using diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI).

Materials and methods: Mice carrying basal-like (MAS98.12) or luminal-like (MAS98.06) orthotopic breast cancer xenografts were treated with bevacizumab (5 mg/kg), doxorubicin (8 mg/kg), or both drugs in combination. DW-MRI and DCE-MRI were performed before and 3 days after treatment using a Bruker 7T preclinical scanner. Mean microvessel density (MVD) and proliferating microvessel density (pMVD) in the tumors were determined for evaluation of vascular response to bevacizumab treatment.

Results: No changes in DCE-MRI or DW-MRI parameters were observed in untreated controls during the experiment period. DW-MRI showed increased apparent diffusion coefficient (ADC) values in all treatment groups in both basal-like and luminal-like xenografts. DCE-MRI showed increased contrast agent uptake, particularly in central regions of the tumors, after bevacizumab/combination treatment in both xenograft models. This was accompanied by decreased MVD and pMVD in basal-like xenografts. Doxorubicin treatment had no effect on DCE-MRI parameters in any of the xenograft models.

Conclusion: Both DW-MRI and DCE-MRI demonstrated an early response to bevacizumab treatment in the xenograft tumors. Increased contrast agent uptake and reduced MVD/pMVD is consistent with a normalization of vascular function.

Keywords: DCE-MRI; DW-MRI; angiogenesis; animal models; breast cancer; gadodiamide.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Contrast Media / chemistry
  • Diffusion Magnetic Resonance Imaging / methods*
  • Doxorubicin / therapeutic use*
  • Mice
  • Molecular Weight
  • Prognosis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Contrast Media
  • Bevacizumab
  • Doxorubicin