TY - JOUR
T1 - Tumor physiologic response to combretastatin A4 phosphate assessed by MRI
AU - Zhao, Dawen
AU - Jiang, Lan
AU - Hahn, Eric W.
AU - Mason, Ralph P.
N1 - Funding Information:
Supported by DOD Breast Cancer IDEA Award (DAMD 170310363) (D.Z.), in conjunction with NCI RO1 CA79515/EB002762 and the Cancer Imaging Program, a P20 Pre-ICMIC CA86354; MRI experiments were performed at the Mary Nell & Ralph B. Rogers MR Center—an NIH BTRP No. P41-RR02584.
PY - 2005/7/1
Y1 - 2005/7/1
N2 - Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19F 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 pO2 (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 pO2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO2 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 <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 pO2 measurements as expected, but quantitative pO2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.
AB - Purpose: To evaluate the effect of the vascular targeting agent, combretastatin A4 phosphate, on tumor oxygenation compared with vascular perfusion/permeability. Methods and Materials: 19F 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 pO2 (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 pO2 in the central and peripheral regions were parallel, but by 24 h after treatment, a significant difference was apparent: the pO2 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 <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 pO2 measurements as expected, but quantitative pO2 measurements are potentially important for optimizing the therapeutic combination of vascular targeting agents with radiotherapy.
KW - Breast tumor
KW - MRI
KW - Oxygenation
KW - Vascular targeting agent
KW - Vasculature
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U2 - 10.1016/j.ijrobp.2005.03.009
DO - 10.1016/j.ijrobp.2005.03.009
M3 - Article
C2 - 15936572
AN - SCOPUS:20344378675
SN - 0360-3016
VL - 62
SP - 872
EP - 880
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -