title: Potential role of hypoxia imaging using (18)F-FAZA PET to guide hypoxia-driven interventions (carbogen breathing or dose escalation) in radiation therapy.
abstract: OBJECTIVE
  Hypoxia-driven intervention (oxygen manipulation or dose escalation) could overcome radiation resistance linked to tumor hypoxia. Here, we evaluated the value of hypoxia imaging using (18)F-FAZA PET to predict the outcome and guide hypoxia-driven interventions.
  
  
  METHODS
  Two hypoxic rat tumor models were used: rhabdomyosarcoma and 9L-glioma. For the irradiated groups, the animals were divided into two subgroups: breathing either room air or carbogen. (18)F-FAZA PET images were obtained just before the irradiation to monitor the hypoxic level of each tumor. Absolute pO2 were also measured using EPR oximetry. Dose escalation was used in Rhabdomyosarcomas.
  
  
  RESULTS
  For 9L-gliomas, a significant correlation between (18)F-FAZA T/B ratio and tumor growth delay was found; additionally, carbogen breathing dramatically improved the tumor response to irradiation. On the contrary, Rhabdomyosarcomas were less responsive to hyperoxic challenge. For that model, an increase in growth delay was observed using dose escalation, but not when combining irradiation with carbogen.
  
  
  CONCLUSIONS
  (18)F-FAZA uptake may be prognostic of outcome following radiotherapy and could assess the response of tumor to carbogen breathing. (18)F-FAZA PET may help to guide the hypoxia-driven intervention with irradiation: carbogen breathing in responsive tumors or dose escalation in tumors non-responsive to carbogen.
authors.affiliation: Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ly-Binh-An
authors.initials: LB
authors.lastname: Tran
authors.affiliation: Institut de Recherches Expérimentales et Cliniques, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.affiliation: Institut de Recherches Expérimentales et Cliniques, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.affiliation: Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Oussama
authors.initials: O
authors.lastname: Karroum
authors.affiliation: Institut de Recherches Expérimentales et Cliniques, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bol
authors.affiliation: Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jordan
authors.affiliation: Institut de Recherches Expérimentales et Cliniques, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. Electronic address: Bernard.Gallez@uclouvain.be.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage*; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy; D008297:Male; D009593:Nitroimidazoles; D010092:Oximetry; D010100:Oxygen / Q000008:administration & dosage* / Q000378:metabolism; D010313:Partial Pressure; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy
chemical_list: D009593:Nitroimidazoles; D002245:Carbon Dioxide; C498052:fluoroazomycin arabinoside; C011700:carbogen; D010100:Oxygen
keywords: (18)F-FAZA; Carbogen; Dose escalation; EPR; Hypoxia