title: Measurement of Tumor Hypoxia in Patients with Advanced Pancreatic Cancer Based on 18F-Fluoroazomyin Arabinoside Uptake.
abstract: Pancreatic cancers are thought to be unusually hypoxic, which might sensitize them to drugs that are activated under hypoxic conditions. In order to develop this idea in the clinic, a minimally invasive technique for measuring the oxygenation status of pancreatic cancers is needed.
  
  
  METHODS
  We tested the potential for minimally invasive imaging of hypoxia in pancreatic cancer patients, using the 2-nitroimidazole PET tracer (18)F-fluoroazomycin arabinoside (or (18)F-1-α-D-[5-fluoro-5-deoxyarabinofuranosyl]-2-nitroimidazole [(18)F-FAZA]). Dynamic and static scans were obtained in 21 patients with either locally advanced or metastatic disease. The hypoxic fraction was determined in the 2-h static scans as the percentage of voxels with SUVs more than 3 SDs from the mean values obtained for skeletal muscle.
  
  
  RESULTS
  Hypoxia was detected in 15 of 20 evaluable patients, with the hypoxic fraction ranging from less than 5% to greater than 50%. Compartmental analysis of the dynamic scans allowed us to approximate the tumor perfusion as mL/min/g of tissue, a value that is independent of the extent of hypoxia derived from tracer uptake in the 2-h static scan. There was no significant correlation between tumor perfusion and hypoxia; nor did we see an association between tumor volume and hypoxia.
  
  
  CONCLUSIONS
  Although pancreatic cancers can be highly hypoxic, a substantial proportion appears to be well oxygenated. Therefore, we suggest that a minimally invasive technique such as the one described in this study be used for patient stratification in future clinical trials of hypoxia-targeting agents.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Metran-Nascente
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Yeung
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and.
authors.forename: Douglass C
authors.initials: DC
authors.lastname: Vines
authors.affiliation: Department of Medical Imaging, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Ur
authors.initials: U
authors.lastname: Metser
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Neesha C
authors.initials: NC
authors.lastname: Dhani
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and.
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and.
authors.forename: David
authors.initials: D
authors.lastname: Jaffray
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada david.hedley@uhn.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000150:complications / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012039:Regional Blood Flow
chemical_list: D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C498052:fluoroazomycin arabinoside
keywords: FAZA; hypoxia; pancreatic cancer; perfusion