Pretargeted dual-modality immuno-SPECT and near-infrared fluorescence imaging for image-guided surgery of prostate cancer

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 intra-operative delineation of tumor resection margins. Since pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intra-operative 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 and a fluorophore (IRdye800CW) for near-infrared fluorescence (NIRF) 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 16h of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either 111In-RDC018 or 111In-IMP288 as a control. Two hours p.i., both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. Subsequently, the biodistribution of 111In-RDC018 and 111In-IMP288 was determined. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2 expressing PC3 tumors (12.4±3.7% ID/g at 2h p.i.), comparable to 111In-IMP288 (9.1±2.8% ID/g at 2h p.i.). MicroSPECT/CT and NIRF imaging confirmed this TROP-2-specific uptake of 111In-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 intra-operative NIRF imaging, showing the preclinical feasibility of the pretargeted dual-modality imaging approach in prostate cancer.