Targeted dual-modality imaging in renal cell carcinoma: An ex vivo kidney perfusion study.

M. Hekman, O. Boerman, M. de Weijert, D. Bos, E. Oosterwijk, J. Langenhuijsen, P. Mulders and M. Rijpkema




Antibodies labeled with both a near-infrared fluorescent dye and a radionuclide can be used for tumor-targeted intraoperative dual-modality imaging. Girentuximab is a chimeric monoclonal antibody against carbonic anhydrase IX (CAIX), an antigen expressed in 95\% of clear cell renal cell carcinoma (ccRCC). This study aimed to assess the feasibility of targeted dual-modality imaging with 111In-girentuximab-IRDye800CW using ex vivo perfusion of human tumorous kidneys.Seven radical nephrectomy specimens of ccRCC patients were perfused during 11-15h with dual-labeled girentuximab and subsequently rinsed during 2.5-4h with Ringer's Lactate solution. Then, dual-modality imaging was performed on a 5-10-mm thick lamella of the kidney. Fluorescence imaging was performed with a clinical fluorescence camera set-up as applied during image-guided surgery. The distribution of Indium-111 in the slice of tumor tissue was visualized by autoradiography. In two perfusions an additional dual-labeled control antibody was added to demonstrate specific accumulation of dual-labeled girentuximab in CAIX-expressing tumor tissue. Results Both radionuclide and fluorescence imaging clearly visualized uptake in tumor tissue and tumor-to-normal tissue borders, as confirmed (immuno)histochemically and by gamma counting. Maximum uptake of girentuximab in tumor tissue was 0.33 \% of the injected dose per gram (mean 0.12 \%ID/g, range 0.01 - 0.33 \%ID/g), while maximum uptake in the normal kidney tissue was 0.04 \%ID/g (mean 0.02 \%ID/g, range 0.00 - 0.04 \%ID/g).Dual-labeled girentuximab accumulated specifically in ccRCC tissue, indicating the feasibility of dual-modality imaging to detect ccRCC. A clinical study to evaluate intraoperative dual-modality imaging in ccRCC patients has been initiated.

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