title: Accessing radiation response using hypoxia PET imaging and oxygen sensitive electrodes: a preclinical study.
abstract: OBJECTIVE
  Tumor hypoxia is a known cause of resistance to radiotherapy. The aim of this study was to investigate the prognostic value of hypoxia measured by (18)F-fluoroazomycin arabinoside ((18)F-FAZA) PET or the Eppendorf oxygen electrode in a pre-clinical tumor model.
  
  
  METHODS
  Pretreatment (18)F-FAZA PET scans and blood sampling was conducted in 92 Female CDF1 mice with subcutaneous C3H mammary carcinomas grown in the right foot. Similarly, oxygenation status of 80 equivalent tumors was assessed using an invasive oxygen sensitive electrode. Tumors were then irradiated with a single dose of 55 Gy and local tumor control up to 90 days after the treatment was determined.
  
  
  RESULTS
  A significant difference in local tumor control between "more hypoxic" or "less hypoxic" groups separated either by a median (18)F-FAZA PET determined tumor-to-blood ratio (P=0.007; hazard ratio, HR=0.21 [95% CI: 0.06-0.74]), or the fraction of oxygen partial pressure (pO(2)) values ≤2.5 mmHg (P=0.018; HR=0.31 [95% CI: 0.11-0.87]), was found. Both assays showed that the more hypoxic tumors had significantly lower tumor control.
  
  
  CONCLUSIONS
  (18)F-FAZA PET analysis showed that pre treatment tumor hypoxia was prognostic of radiation response. Similar results were obtained when oxygenation status was assessed by the Eppendorf pO(2) Histograph. The results of this study support the role of (18)F-FAZA as a non-invasive prognostic marker for tumor hypoxia.
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. lsm@oncology.dk
authors: Lise Saksø
authors: LS
authors: Mortensen
authors: Morten
authors: M
authors: Busk
authors: Marianne
authors: M
authors: Nordsmark
authors: Steen
authors: S
authors: Jakobsen
authors: Jørn
authors: J
authors: Theil
authors: Jens
authors: J
authors: Overgaard
authors: Michael R
authors: MR
authors: Horsman
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D004566:Electrodes; D005260:Female; D005462:Fluorine Radioisotopes; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D051379:Mice; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D011836:Radiation Tolerance
chemical_list: D005462:Fluorine Radioisotopes; D009593:Nitroimidazoles; C498052:fluoroazomycin arabinoside