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Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis
Author(s) -
Black Peter C.,
Shetty Anil,
Brown Gordon A.,
EsparzaCoss Emilio,
Metwalli Adam R.,
Agarwal Piyush K.,
McConkey David J.,
Hazle John D.,
Dinney Colin P.N.
Publication year - 2010
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2010.09424.x
Subject(s) - necrosis , pathology , magnetic resonance imaging , medicine , vascularity , cd31 , hypoxia (environmental) , staining , immunohistochemistry , haematoxylin , nuclear medicine , radiology , chemistry , organic chemistry , oxygen
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. MATERIALS AND 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). CONCLUSION 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.