title: Monitoring Combretastatin A4-induced tumor hypoxia and hemodynamic changes using endogenous MR contrast and DCE-MRI.
abstract: OBJECTIVE
  To benchmark MOBILE (Mapping of Oxygen By Imaging Lipid relaxation Enhancement), a recent noninvasive MR method of mapping changes in tumor hypoxia, electron paramagnetic resonance (EPR) oximetry, and dynamic contrast-enhanced MRI (DCE-MRI) as biomarkers of changes in tumor hemodynamics induced by the antivascular agent combretastatin A4 (CA4).
  
  
  METHODS
  NT2 and MDA-MB-231 mammary tumors were implanted subcutaneously in FVB/N and nude NMRI mice. Mice received 100 mg/kg of CA4 intraperitoneally 3 hr before imaging. The MOBILE sequence (assessing R1 of lipids) and the DCE sequence (assessing K(trans) hemodynamic parameter), were assessed on different cohorts. pO2 changes were confirmed on matching tumors using EPR oximetry consecutive to the MOBILE sequence. Changes in tumor vasculature were assessed using immunohistology consecutive to DCE-MRI studies.
  
  
  RESULTS
  Administration of CA4 induced a significant decrease in lipids R1 (P = 0.0273) on pooled tumor models and a reduction in tumor pO2 measured by EPR oximetry. DCE-MRI also exhibited a significant drop of K(trans) (P < 0.01) that was confirmed by immunohistology.
  
  
  CONCLUSIONS
  MOBILE was identified as a marker to follow a decrease in oxygenation induced by CA4. However, DCE-MRI showed a higher dynamic range to follow changes in tumor hemodynamics induced by CA4.
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Colliez
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Fruytier
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Magat
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Neveu
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Group, Avenue Mounier 73, B1.73.08, Brussels, Belgium.
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D003287:Contrast Media; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D013267:Stilbenes; C058728:fosbretabulin; D010100:Oxygen
keywords: CA4; DCE-MRI; MOBILE; hemodynamics; hypoxia; tumor