title: Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment.
abstract: OBJECTIVE
  The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible "normalization" of the tumor vasculature that could be exploited to improve radiotherapy.
  
  
  METHODS
  Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO(2)) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrast-enhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a "wick-in-needle" technique.
  
  
  RESULTS
  Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling.
  
  
  CONCLUSIONS
  In summary, the microenvironmental changes induced by thalidomide were sufficient to radiosensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization.
authors.affiliation: Laboratories of Biomedical Magnetic Resonance, Université Catholique de Louvain, Avenue E. Mounier 73-40, B-1200 Brussels, Belgium.
authors.forename: Réginald
authors.initials: R
authors.lastname: Ansiaux
authors.forename: Christine
authors.initials: C
authors.lastname: Baudelet
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.forename: Nelson
authors.initials: N
authors.lastname: Beghein
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.forename: Julie
authors.initials: J
authors.lastname: De Wever
authors.forename: Philippe
authors.initials: P
authors.lastname: Martinive
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003287:Contrast Media; D004578:Electron Spin Resonance Spectroscopy; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009997:Osmotic Pressure / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000528:radiation effects; D011836:Radiation Tolerance; D013792:Thalidomide / Q000627:therapeutic use*; D014965:X-Rays
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D013792:Thalidomide; D019786:Gadolinium DTPA; D010100:Oxygen