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.
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 ratbreast 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.
Authors: Deepak K K Kadayakkara; Jelena M Janjic; Lisa K Pusateri; Won-Bin Young; Eric T Ahrens Journal: Magn Reson Med Date: 2010-09-21 Impact factor: 4.668
Authors: Heling Zhou; Rami R Hallac; Ramona Lopez; Rebecca Denney; Matthew T MacDonough; Li Li; Li Liu; Edward E Graves; Mary Lynn Trawick; Kevin G Pinney; Ralph P Mason Journal: Am J Nucl Med Mol Imaging Date: 2015-01-15
Authors: Haichan Niu; Tracy E Strecker; Jeni L Gerberich; James W Campbell; Debabrata Saha; Deboprosad Mondal; Ernest Hamel; David J Chaplin; Ralph P Mason; Mary Lynn Trawick; Kevin G Pinney Journal: J Med Chem Date: 2019-05-24 Impact factor: 7.446