Radionuclide and fluorescence imaging of renal cell carcinoma using dual-label anti-Carbonic Anhydrase IX antibody G250

Objectives 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. In this study, the feasibility of combined fluorescence imaging and radionuclide imaging with a dual-label anti-carbonic anhydrase IX (CAIX) antibody preparation ¹¹¹In-DTPA-G250-IRDye800CW was evaluated in mice with intraperitoneally (i.p.) growing clear cell renal cell carcinoma (ccRCC) lesions.

Methods BALB/c nu/nu mice with i.p. growing SK-RC-52 tumors received 10 μg DTPA-G250-IRDye800CW labeled with 15 MBq ¹¹¹In (n=20) or 10 μg dual-labeled irrelevant control antibody NUH-82 (n=20). To evaluate when tumors could be detected, 4 mice per group were imaged weekly during five weeks with both SPECT/CT and the IVIS Lumina fluorescence imager, followed by ex vivo biodistribution studies.

Results As early as one week after tumor cell inoculation, both SPECT and fluorescence images showed clear delineation of the CAIX-expressing lesions, with very good concordance between the modalities. The high and specific accumulation of ¹¹¹In-DTPA-G250-IRDye800CW in the tumors was confirmed in the biodistribution studies. Maximum tumor uptake was observed one week after inoculation (G250: 58.5±18.7 vs NUH-82: 5.6 ± 2.3 %ID/g), but also on other time points high tumor uptake was observed.

Conclusions This study demonstrates the feasibility of dual modality imaging with dual-labeled antibody ¹¹¹In-DTPA-G250-IRDye800CW in a ccRCC model. Both SPECT and fluorescence images clearly showed specific accumulation of the tracer in the tumors, with excellent concordance between the imaging modalities. These results indicate that pre- and intraoperative detection of CAIX-expressing tumors, positive resection margins, and metastases might be feasible with this approach.