title: Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain.
abstract: OBJECTIVE
  Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model.
  
  
  METHODS
  Tissue responses to MRT (two orthogonal arrays (2 × 400Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR_SO2) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia.
  
  
  RESULTS
  In tumors, MR_SO2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR_SO2, although vessel inter-distances increased slightly.
  
  
  CONCLUSIONS
  We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia.
authors.affiliation: INSERM U836, Grenoble, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bouchet
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lemasson
authors.forename: Thomas
authors.initials: T
authors.lastname: Christen
authors.forename: Marine
authors.initials: M
authors.lastname: Potez
authors.forename: Claire
authors.initials: C
authors.lastname: Rome
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coquery
authors.forename: Céline
authors.initials: C
authors.lastname: Le Clec'h
authors.forename: Anaick
authors.initials: A
authors.lastname: Moisan
authors.forename: Elke
authors.initials: E
authors.lastname: Bräuer-Krisch
authors.forename: Géraldine
authors.initials: G
authors.lastname: Leduc
authors.forename: Chantal
authors.initials: C
authors.lastname: Rémy
authors.forename: Jean A
authors.initials: JA
authors.lastname: Laissue
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Brun
authors.forename: Raphaël
authors.initials: R
authors.lastname: Serduc
mesh_terms: D000818:Animals; D001921:Brain / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000532:radiotherapy*; D018316:Gliosarcoma / Q000098:blood supply / Q000378:metabolism / Q000532:radiotherapy*; D051272:Glucose Transporter Type 1 / Q000032:analysis; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017356:Synchrotrons; D014964:X-Ray Therapy / Q000379:methods*
chemical_list: D051272:Glucose Transporter Type 1; C495679:Slc2a1 protein, rat; D010100:Oxygen
keywords: Brain tumors; MRI; Oxygen saturation; Rat; Synchrotron microbeam radiation therapy; Vessel radiation responses