RT Journal Article SR Electronic T1 Dual-Modality Image-Guided Surgery of Prostate Cancer with a Radiolabeled Fluorescent Anti-PSMA Monoclonal Antibody JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 995 OP 1001 DO 10.2967/jnumed.114.138180 VO 55 IS 6 A1 Susanne Lütje A1 Mark Rijpkema A1 Gerben M. Franssen A1 Giulio Fracasso A1 Wijnand Helfrich A1 Annemarie Eek A1 Wim J. Oyen A1 Marco Colombatti A1 Otto C. Boerman YR 2014 UL http://jnm.snmjournals.org/content/55/6/995.abstract AB Both radionuclide imaging and near-infrared fluorescent (NIRF) imaging have a high sensitivity to detect tumors in vivo. The combination of these modalities using dual-labeled antibodies may allow both preoperative and intraoperative tumor localization and may be used in image-guided surgery to ensure complete resection of tumor tissue. Here, we evaluated the potential of dual-modality imaging of prostate cancer with the monoclonal antibody D2B, directed against an extracellular domain of prostate-specific membrane antigen (PSMA). For these studies, D2B was labeled both with 111In and with the NIRF dye IRDye800CW. Methods: D2B was conjugated with N-hydroxysuccinimide-IRDye800CW and p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (ITC-DTPA) and subsequently radiolabeled with 111In. For biodistribution and NIRF imaging, 111In-DTPA-D2B-IRDye800CW (2 μg, 0.55 MBq/mouse) was injected intravenously into BALB/c nude mice with subcutaneous PSMA-expressing LNCaP tumors (right flank) and PSMA-negative PC3 tumors (left flank). The biodistribution was determined at 1, 2, 3, and 7 d after injection. In addition, micro-SPECT/CT and NIRF imaging with 111In-DTPA-D2B-IRDye800CW (3 μg, 8.5 MBq/mouse) was performed on mice with intraperitoneally growing LS174T-PSMA tumors. Results: 111In-DTPA-D2B-IRDye800CW specifically accumulated in subcutaneous PSMA-positive LNCaP tumors (45.8 ± 8.0 percentage injected dose per gram at 168 h after injection), whereas uptake in subcutaneous PSMA-negative PC3 tumors was significantly lower (6.6 ± 1.3 percentage injected dose per gram at 168 h after injection). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both micro-SPECT/CT and NIRF imaging at 2 d after injection, and the feasibility of image-guided resection of intraperitoneal tumors was demonstrated in this model. Conclusion: Dual-labeled 111In-DTPA-D2B-IRDye800CW enables specific and sensitive detection of prostate cancer lesions in vivo with micro-SPECT/CT and NIRF imaging. In addition to preoperative micro-SPECT/CT imaging to detect tumors, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant clinical studies with 111In-DTPA-D2B-IRDye800CW to improve tumor detection and resection in prostate cancer patients.