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

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 G d and viscosity G l 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*, G d and G l 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), G d (P<0.01) and G l (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. © 2014 Cancer Research UK.