title: In vivo near-infrared spectroscopy and magnetic resonance imaging monitoring of tumor response to combretastatin A-4-phosphate correlated with therapeutic outcome.
abstract: OBJECTIVE
  To develop a combination treatment consisting of combretastatin A-4-phosphate (CA4P) with radiation based on tumor oxygenation status.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9058, USA. Dawen.Zhao@UTSouthwestern.edu
authors.forename: Dawen
authors.initials: D
authors.lastname: Zhao
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Chang
authors.forename: Jae G
authors.initials: JG
authors.lastname: Kim
authors.forename: Hanli
authors.initials: H
authors.lastname: Liu
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015687:Cell Hypoxia; D003131:Combined Modality Therapy / Q000379:methods; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy*; D009336:Necrosis / Q000097:blood; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood*; D010108:Oxyhemoglobins / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D019265:Spectroscopy, Near-Infrared; D013267:Stilbenes / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006454:Hemoglobins; D010108:Oxyhemoglobins; D013267:Stilbenes; C058728:fosbretabulin; D010100:Oxygen