Monitoring Tumor Response to Antivascular Therapy Using Non-Contrast Intravoxel Incoherent Motion Diffusion-Weighted MRI

Cancer Res. 2017 Jul 1;77(13):3491-3501. doi: 10.1158/0008-5472.CAN-16-2499. Epub 2017 May 9.

Abstract

Antivascular therapy is a promising approach to the treatment of non-small cell lung cancer (NSCLC), where an imaging modality capable of longitudinally monitoring treatment response could provide early prediction of the outcome. In this study, we sought to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion MRI to quantitatively assess the efficacy of the treatments of a vascular-disrupting agent CA4P or its combination with bevacizumab on experimental NSCLC tumors. CA4P caused a strong but reversible effect on tumor vasculature; all perfusion-related parameters-D*, f, fD*, and Ktrans-initially showed a decrease of 30% to 60% at 2 hours and then fully recovered to baseline on day 2 for CA4P treatment or on days 4 to 8 for CA4P + bevacizumab treatment; the diffusion coefficient in tumors decreased initially at 2 hours and then increased from day 2 to day 8. We observed a good correlation between IVIM parameters and dynamic contrast-enhanced MRI (DCE-MRI; Ktrans). We also found that the relative change in f and fD* at 2 hours correlated well with changes in tumor volume on day 8. In conclusion, our results suggest that IVIM is a promising alternative to DCE-MRI for the assessment of the change in tumor perfusion as a result of antivascular agents and can be used to predict the efficacy of antivascular therapies without the need for contrast media injection. Cancer Res; 77(13); 3491-501. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Angiogenesis Inhibitors / administration & dosage
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Bevacizumab / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Diffusion Magnetic Resonance Imaging / methods*
  • Humans
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Motion
  • Random Allocation
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Stilbenes
  • Bevacizumab
  • fosbretabulin