title: Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis.
abstract: OBJECTIVE
  To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy.
  
  
  METHODS
  Orthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1-mm step-sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified.
  
  
  RESULTS
  The correlation between MRI volume and BLI was weak in KU7 xenografts (R(2) < 0.1) but strong in 253J B-V (R(2) = 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R(2) = 0.42).
  
  
  CONCLUSIONS
  The correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method.
authors.affiliation: Department of Urology, University of Texas, M.D. Anderson Cancer Center, TX, USA. peter.black@ubc.ca
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
authors.forename: Anil
authors.initials: A
authors.lastname: Shetty
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Brown
authors.forename: Emilio
authors.initials: E
authors.lastname: Esparza-Coss
authors.forename: Adam R
authors.initials: AR
authors.lastname: Metwalli
authors.forename: Piyush K
authors.initials: PK
authors.lastname: Agarwal
authors.forename: David J
authors.initials: DJ
authors.lastname: McConkey
authors.forename: John D
authors.initials: JD
authors.lastname: Hazle
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D000860:Hypoxia; D007150:Immunohistochemistry; D049449:Luminescence; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000473:pathology*