Pre-clinical assessment of anti-vascular drugs using quantitative dynamic contrast-enhanced MRI

The effect of novel anti-cancer agents on the vascular properties of radiation-induced fibrosarcomas in C3H-strain mice was evaluated in vivo using dynamic contrast-enhanced (DCE) MRI. A T1-weighted volume acquisition was used to obtain DCE-MRI data. Pre-contrast T1 measurements and the contrast agent arterial input function were used to estimate the volume transfer constant (Ktrans) and extravascular extracellular volume fraction (ve). Five novel combretastatin analogues, combretastatin A-4 (CA-4) and hazelnut oil (vehicle) were tested for their effect 24 hours after administration on the tumours. Three of the five agents and the positive control (CA-4), significantly decreased tumour Ktrans and ve: Ktrans for CA-4 by 72%; fluorocombretastatin by 75%; methylcombretastatin by 68%; and ve by 40% for methylcombretastatin and 75% for the combretastatin quinone. These agents were recommended for further consideration. These results suggest that DCE-MRI may be a useful tool for pre-clinical evaluation of anti-...