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

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 mgkg(-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*| (Po0.01), 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.