Targeted Dual-Modality Imaging in Renal Cell Carcinoma: An Ex Vivo Kidney Perfusion Study.
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 (111)In-girentuximab-IRDye800CW using ex vivo perfusion of human tumorous kidneys.



Seven radical nephrectomy specimens from patients with ccRCC were perfused during 11 to 15 hours with dual-labeled girentuximab and subsequently rinsed during 2.5 to 4 hours with Ringer's Lactate solution. Then, dual-modality imaging was performed on a 5- to 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.



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), whereas 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 patients with ccRCC has been initiated. Clin Cancer Res; 22(18); 4634-42. ©2016 AACR.
Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands. Department of Urology, Radboudumc, Nijmegen, the Netherlands. marlene.hekman@radboudumc.nl.
Marlène C H
MC
Hekman
Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands.
Otto C
OC
Boerman
Department of Urology, Radboudumc, Nijmegen, the Netherlands.
Mirjam
M
de Weijert
Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands.
Desirée L
DL
Bos
Department of Urology, Radboudumc, Nijmegen, the Netherlands.
Egbert
E
Oosterwijk
Department of Urology, Radboudumc, Nijmegen, the Netherlands.
Hans F
JF
Langenhuijsen
Department of Urology, Radboudumc, Nijmegen, the Netherlands.
Peter F A
PF
Mulders
Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands.
Mark
M
Rijpkema
D000911:Antibodies, Monoclonal; D001557:Benzenesulfonates; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles; D007457:Iodine Radioisotopes; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D008856:Microscopy, Fluorescence; D009367:Neoplasm Staging; D009392:Nephrectomy; D055420:Perfusion Imaging / Q000379:methods; D047368:Tumor Burden
D000911:Antibodies, Monoclonal; D001557:Benzenesulfonates; C106533:G250 monoclonal antibody; C562366:IRDye 800CW; D007211:Indoles; D007457:Iodine Radioisotopes