Dual-Modality Image-Guided Surgery of Prostate Cancer with a Radiolabeled Fluorescent Anti-PSMA Monoclonal Antibody

J Nucl Med. 2014 Jun;55(6):995-1001. doi: 10.2967/jnumed.114.138180. Epub 2014 Apr 3.


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 (111)In 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 (111)In. For biodistribution and NIRF imaging, (111)In-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 (111)In-DTPA-D2B-IRDye800CW (3 μg, 8.5 MBq/mouse) was performed on mice with intraperitoneally growing LS174T-PSMA tumors.

Results: (111)In-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 (111)In-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 (111)In-DTPA-D2B-IRDye800CW to improve tumor detection and resection in prostate cancer patients.

Keywords: D2B IgG; IRDye800CW; PSMA; dual-modality imaging; fluorescence imaging; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antigens, Surface / immunology*
  • Benzenesulfonates / chemistry*
  • Binding, Competitive
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Fluorescent Dyes / chemistry
  • Glutamate Carboxypeptidase II / immunology*
  • Humans
  • Indium Radioisotopes
  • Indoles / chemistry*
  • Isotope Labeling
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Optical Imaging
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery*
  • Surgery, Computer-Assisted / methods*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed


  • Antibodies, Monoclonal
  • Antigens, Surface
  • Benzenesulfonates
  • Fluorescent Dyes
  • IRDye 800CW
  • Indium Radioisotopes
  • Indoles
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II