In vivo near-infrared spectroscopy and magnetic resonance imaging monitoring of tumor response to combretastatin a-4-phosphate correlated with therapeutic outcome

Dawen Zhao, Cheng Hui Chang, Jae G. Kim, Hanli Liu, Ralph P. Mason

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Purpose: To develop a combination treatment consisting of combretastatin A-4-phosphate (CA4P) with radiation based on tumor oxygenation status. Methods and Materials: In vivo near-infrared spectroscopy (NIRS) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were applied to noninvasively monitor changes in tumor blood oxygenation and necrosis induced by CA4P (30 mg/kg) in rat mammary 13762NF adenocarcinoma, and the evidence was used to optimize combinations of CA4P and radiation treatment (a single dose of 5 Gy). Results: NIRS showed decreasing concentrations of tumor vascular oxyhemoglobin and total hemoglobin during the first 2 h after CA4P treatment, indicating significant reductions in tumor blood oxygenation and perfusion levels (p < 0.001). Twenty-four hours later, in response to oxygen inhalation, significant recovery was observed in tumor vascular and tissue oxygenation according to NIRS and pimonidazole staining results, respectively (p < 0.05). DW MRI revealed significantly increased water diffusion in tumors measured by apparent diffusion coefficient at 24 h (p < 0.05), suggesting that CA4P-induced central necrosis. In concordance with the observed tumor oxygen dynamics, we found that treatment efficacy depended on the timing of the combined therapy. The most significant delay in tumor growth was seen in the group of tumors treated with radiation while the rats breathed oxygen 24 h after CA4P administration. Conclusions: Noninvasive evaluation of tumor oxygen dynamics allowed us to rationally enhance the response of syngeneic rat breast tumors to combined treatment of CA4P with radiation.

Original languageEnglish (US)
Pages (from-to)574-581
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume80
Issue number2
DOIs
StatePublished - Jun 1 2011

Keywords

  • Combretastatin A-4-phosphate
  • Diffusion-weighted MRI
  • Hypoxia
  • Near-infrared spectroscopy
  • Radiation

ASJC Scopus subject areas

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

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