title: PET imaging of tumor hypoxia using 18F-fluoroazomycin arabinoside in stage III-IV non-small cell lung cancer patients.
abstract: Tumor hypoxia hampers the efficacy of radiotherapy because of its increased resistance to ionizing radiation. The aim of the present study was to estimate the potential added clinical value of the specific hypoxia tracer (18)F-fluoroazomycin arabinoside ((18)F-FAZA) over commonly used (18)F-FDG in the treatment of advanced-stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Eleven patients with stage III or stage IV NSCLC underwent (18)F-FDG and (18)F-FAZA PET before chemoradiotherapy. The maximum standardized uptake value (SUVmax) was used to depict (18)F-FDG uptake, and the tumor-to-background (T/B) ratio and tumor fractional hypoxic volume (FHV) were used to quantify hypoxia. The spatial correlation between (18)F-FDG and (18)F-FAZA uptake values was investigated using voxel-based analysis. Partial-volume correction was applied.
  
  
  RESULTS
  All 11 patients showed clear uptake of (18)F-FAZA in the primary tumor. However, different patterns of (18)F-FDG and (18)F-FAZA uptake distributions were observed and varied widely among different tumors. No significant correlation was observed between (18)F-FDG SUVmax and (18)F-FAZA T/B ratio (P = 0.055). The median FHV of 1.4 was 48.4% (range, 5.0-91.5). A significant positive correlation was found between the (18)F-FAZA T/B ratio and FHV of 1.4 (P < 0.001). There was no correlation between the lesion size and FHV or between the (18)F-FDG SUVmax and FHV. The pattern of tumoral (18)F-FDG uptake was rather homogeneous, whereas (18)F-FAZA uptake was more heterogeneous, suggesting that (18)F-FAZA identifies hypoxic areas within metabolically active areas of tumor. A significant correlation between (18)F-FDG SUVmax and lesion size (P = 0.002) was observed.
  
  
  CONCLUSIONS
  (18)F-FAZA PET imaging is able to detect heterogeneous distributions of hypoxic subvolumes out of homogeneous (18)F-FDG background in a clinical setting. Therefore, (18)F-FAZA might be considered a tool for guiding dose escalation to the hypoxic fraction of the tumor.
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Bollineni
authors.forename: Gerald S M A
authors.initials: GS
authors.lastname: Kerner
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.forename: Roel J H M
authors.initials: RJ
authors.lastname: Steenbakkers
authors.forename: Erwin M
authors.initials: EM
authors.lastname: Wiegman
authors.forename: Michel J B
authors.initials: MJ
authors.lastname: Koole
authors.forename: Eleonore H
authors.initials: EH
authors.lastname: de Groot
authors.forename: Antoon T M
authors.initials: AT
authors.lastname: Willemsen
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.forename: Joachim
authors.initials: J
authors.lastname: Widder
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000473:pathology*; D015687:Cell Hypoxia; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography; D047368:Tumor Burden
chemical_list: D009593:Nitroimidazoles; D019788:Fluorodeoxyglucose F18; C498052:fluoroazomycin arabinoside
keywords: 18F-FAZA; 18F-FDG; PET; PET/CT; oncology; respiratory; tumor hypoxia