The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability

The acute effects of the antivascular drug, combretastatin A4 phosphate, on tumor energy status and perfusion were assessed using magnetic resonance i maging (MRI) and spectroscopy. Localized P-31 magnetic resonance spectrosco py showed that LoVo and RIF-I tumors responded well to drug treatment, with significant increases in the P-i/nucleoside triphosphate ratio within 3 h, whereas SaS, SaF, and HT29 tumors did not respond to the same extent. This variable response was also seen in MRI experiments in which tumor perfusio n was assessed by monitoring the kinetics of inflow of the contrast agent, gadolinium diethylenetriaminepentaacetate. These data were analyzed to give the initial rate and time constant for inflow of contrast agent and the in tegral under the inflow curve. The differential susceptibility of the tumor s to combretastatin A4 phosphate showed a positive correlation with prior M RI measurements of tumor vascular permeability, which was determined by mea suring the inflow of a macromolecular contrast agent, BSA-gadolinium diethy lenetriaminepentaacetate.