Tumor physiologic response to combretastatin A4 phosphate assessed by MRI

Dawen Zhao, Lan Jiang, Eric W. Hahn, Ralph P. Mason

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)872-880
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume62
Issue number3
DOIs
StatePublished - Jul 1 2005

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Keywords

  • Breast tumor
  • MRI
  • Oxygenation
  • Vascular targeting agent
  • Vasculature

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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