Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

S. Lütje, M. Rijpkema, D. Goldenberg, C. van Rij, R. Sharkey, W. McBride, G. Franssen, C. Frielink, W. Helfrich, W. Oyen and O. Boerman

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Sep, 2014



Radical removal of malignant lesions may be improved using tumor-targeted dual-modality probes that contain both a radiotracer and a fluorescent label to allow for enhanced intraoperative delineation of tumor resection margins. Because pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intraoperative imaging in prostate cancer using an anti-TROP-2 x anti-HSG bispecific antibody (TF12) in conjunction with the dual-labeled diHSG peptide (RDC018) equipped with both a DOTA chelate for radiolabeling purposes and a fluorophore (IRdye800CW) to allow near-infrared optical imaging. Nude mice implanted s.c. with TROP-2-expressing PC3 human prostate tumor cells or with PC3 metastases in the scapular and suprarenal region were injected i.v. with 1 mg of TF12 and, after 16 hours of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either (111)In-RDC018 or (111)In-IMP288 as a control. Two hours after injection, both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. After image acquisition, the biodistribution of (111)In-RDC018 and (111)In-IMP288 was determined and tumors were analyzed immunohistochemically. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2-expressing PC3 tumors (12.4 ± 3.7\% ID/g at 2 hours postinjection), comparable with (111)In-IMP288 (9.1 ± 2.8\% ID/g at 2 hours postinjection). MicroSPECT/CT and near-infrared fluorescence (NIRF) imaging confirmed this TROP-2-specific uptake of the dual-label (111)In-RDC018 in both the s.c. and metastatic growing tumor model. In addition, PC3 metastases could be visualized preoperatively with SPECT/CT and could subsequently be resected by image-guided surgery using intraoperative NIRF imaging, showing the preclinical feasibility of pretargeted dual-modality imaging approach in prostate cancer. Cancer Res; 74(21); 1-8. ©2014 AACR.