Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19 F MRI oximetry and dynamic contrast-enhanced (DCE)-MRI were used to monitor tumor oxygenation and perfusion/permeability in syngeneic 13762NF rat breast carcinoma. Results: A significant drop was found in the mean tumor pO 2 (23 to 9 mm Hg, p p 2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO 2 in the periphery had improved significantly, and the center remained hypoxic. These data are consistent with DCE-MRI, which revealed an ∼70% decrease in perfusion/permeability (initial area under signal-intensity curve) at 2 h ( p Conclusion: The response observed by DCE-MRI, indicating vascular shutdown, paralleled the pO 2 measurements as expected, but quantitative pO 2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.