Tumor physiologic response to combretastatin A4 phosphate assessed by MRI
Dawen Zhao1, Lan Jiang, Eric W Hahn
1Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9058, USA.
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 <0.05) within 90 min after treatment (30 mg/kg of combretastatin A4 phosphate) and a further decrease was observed at 2 h (mean 2 mm Hg; p <0.01). The initial changes in pO(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 approximately 70% decrease in perfusion/permeability (initial area under signal-intensity curve) at 2 h (p <0.001). The initial area under signal-intensity curve recovered fully after 24 h in a thin peripheral region, but not in the tumor center.
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.
