Tumor physiologic response to combretastatin A4 phosphate assessed by MRI.
OBJECTIVE
To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability.


METHODS
(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.


CONCLUSIONS
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.
Zhao
Dawen
D
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9058, USA.
Jiang
Lan
L
Hahn
Eric W
EW
Mason
Ralph P
RP
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015687:Cell Hypoxia; D005260:Female; D005461:Fluorine / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000378:metabolism*; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010313:Partial Pressure; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D005461:Fluorine; C058728:fosbretabulin; D010100:Oxygen