title: Predictive value of (18)F-FAZA PET imaging for guiding the association of radiotherapy with nimorazole: a preclinical study.
abstract: OBJECTIVE
  To assess the predictive value of hypoxia imaging by (18)F-FAZA PET in identifying tumors that may benefit from radiotherapy combined with nimorazole, a hypoxic radiosensitizer.
  
  
  METHODS
  Rats of two tumor models (Rhabdomyosarcoma and 9L-glioma) were divided into two treated groups: radiotherapy (RT) alone or RT plus nimorazole. (18)F-FAZA PET images were obtained to evaluate tumor hypoxia before the treatment. Treatment outcome was assessed through the tumor growth time assay, defined as the time required for tumor to grow to 1.5 times its size before irradiation.
  
  
  RESULTS
  For rhabdomyosarcomas, the benefit of adding nimorazole to RT was not significant when considering all tumors. When stratifying into more and less hypoxic tumors according to the median (18)F-FAZA T/B ratio, we found that the combined treatment significantly improved the response of the "more hypoxic" subgroup, while there was no significant difference in the tumor growth time between the two treatment modalities for the "less hypoxic" subgroup. For 9L-gliomas, a clear benefit was demonstrated for the group receiving RT+nimorazole. However, the individual responses within the RT+nimorazole group were highly variable and independent of the (18)F-FAZA uptake.
  
  
  CONCLUSIONS
  (18)F-FAZA PET may be useful to guide hypoxia-directed RT using nimorazole as radiosensitizer. It identified a subgroup of more hypoxic tumors (displaying T/B ratio>2.72) that would benefit from this combined treatment. Nevertheless, the predictive power was limited to rhabdomyosarcomas and ineffective for 9L-gliomas.
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, 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, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.affiliation: Institut de Recherches Expérimentales et Cliniques, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Thanh-Trang
authors.initials: TT
authors.lastname: Cao-Pham
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jordan
authors.affiliation: Institut de Recherches Expérimentales et Cliniques, Center for Molecular Imaging, Radiotherapy and Oncology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, 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; D015687:Cell Hypoxia / Q000502:physiology; D059248:Chemoradiotherapy; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D009554:Nimorazole / Q000494:pharmacology*; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
chemical_list: D005462:Fluorine Radioisotopes; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C498052:fluoroazomycin arabinoside; D009554:Nimorazole
keywords: (18)F-FAZA; Hypoxia; Nimorazole; Predictive marker; Radiotherapy