Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo assessed by magnetic resonance elastography

Br J Cancer. 2014 Apr 2;110(7):1727-32. doi: 10.1038/bjc.2014.76. Epub 2014 Feb 25.

Abstract

Background: Magnetic resonance elastography (MRE) is an emerging imaging technique that affords non-invasive quantitative assessment and visualization of tissue mechanical properties in vivo.

Methods: In this study, MRE was used to quantify (kPa) the absolute value of the complex shear modulus |G*|, elasticity Gd and viscosity Gl of SW620 human colorectal cancer xenografts before and 24 h after treatment with either 200 mg kg(-1) of the vascular disrupting agent ZD6126 (N-acetylcolchinol-O-phosphate) or vehicle control, and the data were compared with changes in water diffusivity measured by diffusion-weighted magnetic resonance imaging.

Results: A heterogeneous distribution of |G*|, Gd and Gl was observed pre-treatment with an intertumoral coefficient of variation of 13% for |G*|. There were no significant changes in the vehicle-treated cohort. In contrast, ZD6126 induced a significant decrease in the tumour-averaged |G*| (P<0.01), Gd (P<0.01) and Gl (P<0.05), and this was associated with histologically confirmed central necrosis. This reduction in tumour viscoelasticity occurred at a time when no significant change in tumour apparent diffusion coefficient (ADC) was observed.

Conclusions: These data demonstrate that MRE can provide early imaging biomarkers for treatment-induced tumour necrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Biomechanical Phenomena
  • Colonic Neoplasms / blood supply*
  • Colonic Neoplasms / diagnostic imaging
  • Colonic Neoplasms / drug therapy*
  • Elasticity
  • Elasticity Imaging Techniques / methods*
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Necrosis / chemically induced
  • Organophosphorus Compounds / therapeutic use*
  • Shear Strength
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • N-acetylcochinol-O-phosphate
  • Organophosphorus Compounds