title: Non-invasive evaluation of tumour hypoxia in the Shionogi tumour model for prostate cancer with 18F-EF5 and positron emission tomography.
abstract: OBJECTIVE
  To evaluate hypoxia non-invasively in androgen-dependent (AD), regressing (6-days after castration, RG) and androgen-independent (AI) Shionogi tumours, using the radiolabelled tracer for hypoxia, 18F-EF5, and positron emission tomography (PET).
  
  
  METHODS
  Groups of mice bearing AD, RG and AI Shionogi tumours were co-injected with 18F-EF5 and unlabelled EF5. The mice were imaged non-invasively with PET to examine the accumulation of 18F-EF5 in hypoxic regions of the tumour. The tumours were subsequently placed in a gamma-counter, or disaggregated for flow cytometry, to determine the levels of 18F-EF5 and the percentage of hypoxic cells present in the tumour, respectively.
  
  
  RESULTS
  The mean (sd) levels of hypoxia in AD Shionogi tumours decreased significantly 6 days after androgen ablation as measured by flow cytometry, from 17.1 (4.77) to 1.74 (0.46)% (P=0.003). There were no significant differences in the levels of 18F-EF5 in the tissue between AD and RG tumours using region-of-interest analysis of PET images or gamma-counting, although the differences were significant when measured by flow cytometry. However, mean (sd) levels of hypoxia in AI Shionogi tumours were significantly higher than in AD tumours regardless of the analysis method; PET, 10.5 (4.93)x10(-5)) Bq/cm2 (P=0.017), flow cytometry, 42.98 (3.35)% (P<0.001), well count, 6.81 (1.17)x10(4) and 13.1 (1.99)x10(4) cpm/g, for AD and AI tumours, respectively (P<0.001).
  
  
  CONCLUSIONS
  Differences in hypoxia between AD and AI, but not RG, Shionogi tumours can be detected non-invasively with 18F-EF5 and PET. As prostate tumours are hypoxic and the oxygen levels can change with androgen ablation, noninvasive imaging of hypoxia with PET and 18F-EF5 might ultimately have a prognostic and/or diagnostic role in the clinical management of the disease.
authors.affiliation: The Department of Advanced Therapeutics, BC Cancer Agency, Vancouver, Canada. dyapp@bccrc.ca
authors.forename: Donald T T
authors.initials: DT
authors.lastname: Yapp
authors.forename: Janet
authors.initials: J
authors.lastname: Woo
authors.forename: Aileen
authors.initials: A
authors.lastname: Kartono
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sy
authors.forename: Thomas
authors.initials: T
authors.lastname: Oliver
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Skov
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Koch
authors.forename: Hans
authors.initials: H
authors.lastname: Adomat
authors.forename: Wieslawa H
authors.initials: WH
authors.lastname: Dragowska
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Ladan
authors.initials: L
authors.lastname: Fadzli
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruth
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Adam
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage; D000728:Androgens / Q000378:metabolism; D000818:Animals; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D010100:Oxygen