title: Investigation on tumor hypoxia in resectable primary prostate cancer as demonstrated by 18F-FAZA PET/CT utilizing multimodality fusion techniques.
abstract: OBJECTIVE
  As hypoxia is believed to play an important role in the development and progression of prostate cancer, we evaluated whether 18F-labeled fluoroazomycin arabinoside (18F-FAZA) would be useful to identify tumor hypoxia in resectable prostate cancer.
  
  
  METHODS
  Positron emission tomography (PET)/CT was performed on 14 patients with untreated localized primary prostate cancer 3 h post-injection of approximately 390 MBq of 18F-FAZA using forced diuresis to decrease radioactivity in the urinary bladder. Anatomical trans-pelvic coil and pre- and post-contrast 1.5 T MRI with endorectal coil were performed on the same day. Patients underwent radical prostatectomy and ex vivo 3 T MRI of the prostatectomy specimen within 14 days following in vivo imaging. Imaging results were verified by whole mount histopathology plus tissue microarray (TMA) immunohistochemical (IHC) analysis for carbonic anhydrase IX (CAIX) and hypoxia-inducible factor 1α (HIF-1α). Registration of in vivo imaging with histology was achieved using mutual information software and performing ex vivo MRI of the prostatectomy specimen and whole mount sectioning with block face photography as intermediate steps.
  
  
  RESULTS
  Whole mount histology identified 43 tumor nodules, 19 of them larger than 1 ml as determined on coregistered volumes featuring 18F-FAZA, MRI, and histological 3-D image information. None of these lesions was found to be positive for CAIX or visualized by 18F-FAZA PET/CT while IHC for HIF-1α showed variable staining of tumor tissues. Accordingly, no correlation was found between 18F-FAZA uptake and Gleason scores.
  
  
  CONCLUSIONS
  Our data based on 18F-FAZA PET/CT and CAIX IHC do not support the presence of clinically relevant hypoxia in localized primary prostate cancer including high-grade disease. Activation of HIF-1α may be independent of tissue hypoxia in primary prostate cancer.
authors.affiliation: Department of Radiology, Division of Nuclear Medicine, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Garcia-Parra
authors.forename: David
authors.initials: D
authors.lastname: Wood
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Hero
authors.initials: H
authors.lastname: Hussain
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Park
authors.forename: Timothy
authors.initials: T
authors.lastname: Desmond
authors.forename: Charles
authors.initials: C
authors.lastname: Meyer
authors.forename: Morand
authors.initials: M
authors.lastname: Piert
mesh_terms: D000368:Aged; D015687:Cell Hypoxia; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed
chemical_list: D009593:Nitroimidazoles; C498052:fluoroazomycin arabinoside