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In vivo tumour hypoxia and carbonic anhydrase IX expression in xenografted human renal cell carcinoma animal models using probes, 124 I‐G250 pet, biodistribution and immunohistochemistry immunobiodistribution, and oxygen studies
Author(s) -
LAWRENTSCHUK N.,
MURONE C.,
RIGOPOLOUS A.,
MOUNTAIN A.,
O'KEEFE G.,
JONES G.,
LEE F.T.,
DAVIS I.D.,
SCOTT A.M.,
BOLTON D.M.
Publication year - 2006
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.2006.06085_34.x
Subject(s) - biodistribution , immunohistochemistry , hypoxia (environmental) , tumor hypoxia , in vivo , angiogenesis , pathology , renal cell carcinoma , cancer research , monoclonal antibody , positron emission tomography , chemistry , medicine , nuclear medicine , biology , antibody , radiation therapy , oxygen , immunology , microbiology and biotechnology , organic chemistry
Hypoxia stimulates angiogenesis and has been demonstrated in tumours where it correlates with resistance to treatment and poor prognosis. We have previously demonstrated hypoxia in human Renal Cell Carcinoma (RCC). The purpose of animal models was to further evaluate oxygen levels within RCC whilst also focusing on expression of the protein carbonic anhydrase IX (CA IX). This protein is stimulated by hypoxia and involved in angiogenesis and may be a potential tumour target for imaging and future therapies. Methods: Balb/c nude mice had human RCC (SK‐RC‐52) xenografted subcutaneously. Tumours were grown to different volumes with oxygen levels measured. Further groups then had the radiolabelled monoclonal antibody 124 I‐G250 (that binds to CA IX) injected intravenously and had Positron Emission Tomography (PET), gamma counting and oxygen studies performed on days 0,1,2,3,5,7,10 and 14 post injection. Immunohistochemistry and autoradiography was also performed. Results: An inverse relationship between tumour volume and hypoxia within the model was established ( P < 0.001). Furthermore, CA IX was expressed by tumours with maximal uptake of 124 I‐G250 on days 2/3 by distribution with gamma counting that could be correlated with uptake on PET imaging. Conclusions: The xenograft model confirms human RCC are hypoxic. Also, that the level of hypoxia is inversely proportional to tumour sise. A correlation was made between PET scanning with 124 I‐G250 and biodistribution within tumours by gamma counting confirming CAIX as an imaging and potential therapeutic target in RCC.