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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Apr 21 [Epub ahead of print]
Marlene C H Hekman, Otto C Boerman, Mirjam C A de Weijert, Desirée L Bos, Egbert Oosterwijk, Johan F Langenhuijsen, Peter F A Mulders, Mark Rijpkema
Radiology and Nuclear Medicine, Radboudumc ., Radiology and Nuclear Medicine, Radboud University Medical Centre., Urology, Radboud University Medical Centre., Nuclear Medicine, Radboud University Medical Center., Urology, Radboud University Medical Center., Urology, Radboud University Medical Center., Urology, Radboud University Medical Center., Radiology and Nuclear Medicine, Radboud University Medical Center.