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Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250

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Muselaers C.H.J., Rijpkema M., Bos D.L., Langenhuijsen J.F., Oyen W.J.G., Mulders P.F.A., Oosterwijk E., Boerman O.C.

Journal of Urology 2015

Purpose: Tumor targeted optical imaging using antibodies labeled with near infrared fluorophores is a sensitive imaging modality that might be used during surgery to assure complete removal of malignant tissue. We evaluated the feasibility of dual modality imaging and image guided surgery with the dual labeled anti-carbonic anhydrase IX antibody preparation <sup>111</sup>In-DTPA-G250-IRDye800CW in mice with intraperitoneal clear cell renal cell carcinoma. Materials and Methods: BALB/c nu/nu mice with intraperitoneal SK-RC-52 lesions received 10 ?g DTPA-G250-IRDye800CW labeled with 15 MBq <sup>111</sup>In or 10 ?g of the dual labeled irrelevant control antibody NUH-82 (20 mice each). Toevaluate when tumors could be detected, 4 mice per group were imaged weekly during 5 weeks with single photon emission computerized tomography/computerized tomography and the fluorescence imaging followed by exvivo biodistribution studies. Results: As early as 1 week after tumor cell inoculation single photon emission computerized tomography and fluorescence images showed clear delineation of intraperitoneal clear cell renal cell carcinoma with good concordance between single photon emission computerized tomography/computerized tomography and fluorescence images. The high and specific accumulation of the dual labeled antibody conjugate in tumors was confirmed in the biodistribution studies. Maximum tumor uptake was observed 1 week after inoculation (mean ± SD 58.5% ± 18.7% vs 5.6% ± 2.3% injected dose per gm for DTPA-G250-IRDye800CW vs NUH-82, respectively). High tumor uptake was also observed at other time points. Conclusions: This study demonstrates the feasibility of dual modality imaging with dual labeled antibody <sup>111</sup>In-DTPA-G250-IRDye800CW in a clear cell renal cell carcinoma model. Results indicate that preoperative and intraoperative detection of carbonic anhydrase IX expressing tumors, positive resection margins and metastasis might be feasible with this approach.

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