Dual modality imaging of PSMA-expressing prostate cancer with a new radiolabeled anti-PSMA monoclonal antibody conjugated with IRDye800CW

Aim: Both radionuclide and near-infrared fluorescence imaging have a high sensitivity to detect tumor lesions in vivo. The combination of these modalities using dual labeled antibodies may allow both preoperative tumor identification and intraoperative delineation of tumor lesions using real-time image-guided surgery. Here, we evaluated the prostate cancer targeting characteristics of the new monoclonal antibody D2B, directed against an extracellular domain of prostate-specific membrane antigen (PSMA). D2B was labeled both with 111In and with the near-infrared fluorescent dye IRDye800CW. Results and Conclusion: The immunoreactive fractions of 111In-DTPA-D2B-IRDye800CW and 111In-DTPA-D2B on B16-PSMA cells were 71.9% and 82.4%, respectively. 111In-DTPA-D2B-IRDye800CW specifically accumulated in the s.c. PSMA+ B16-PSMA tumors with an uptake ranging from 55.7 %ID/g at 24 h p.i. to 69.8 %ID/g at 72 h p.i., while tumor uptake in PSMA- B16-wildtype xenografts was much lower at all time points (6.27 %ID/g at 24 h p.i. to 4.23 %ID/g at 72 h p.i.). Highest uptake of 111In-DTPA-D2B-IRDye800CW was observed at 72 h after injection. In conclusion, in this first proof-of-principle study, we showed that dual-label 111In-DTPA-D2B-IRDye800CW can be used for specific and sensitive detection of prostate cancer lesions in vivo. While the 111In label allows preoperative delineation of tumor lesions, fluorescent imaging adds the possibility for real-time image guided surgery. These preclinical findings encourage future clinical studies with 111In-DTPA-D2B- IRDye800CW for pre- and intraoperative guidance for resection of prostate cancer lesions.