title: Pretargeted dual-modality immuno-SPECT and near-infrared fluorescence imaging for image-guided surgery of prostate cancer.
abstract: 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.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. Susanne.Lutje@radboudumc.nl.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lütje
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Rijpkema
authors.affiliation: Immunomedics, Morris Plains, New Jersey.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Catharina M
authors.initials: CM
authors.lastname: van Rij
authors.affiliation: Immunomedics, Morris Plains, New Jersey.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.affiliation: Immunomedics, Morris Plains, New Jersey.
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Cathelijne
authors.initials: C
authors.lastname: Frielink
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Surgery, Laboratory for Translation Surgical Oncology, Groningen, the Netherlands.
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000637:transplantation; D003952:Diagnostic Imaging; D005453:Fluorescence; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D011859:Radiography; D019265:Spectroscopy, Near-Infrared; D025321:Surgery, Computer-Assisted; D015899:Tomography, Emission-Computed, Single-Photon