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

Susanne Lutje*, Mark Rijpkema, Gerben M. Franssen, Giulio Fracasso, Wijnand Helfrich, Annemarie Eek, Wim J. Oyen, Marco Colombatti, Otto C. Boerman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)995-1001
Number of pages7
JournalJournal of Nuclear Medicine
Volume55
Issue number6
DOIs
Publication statusPublished - Jun-2014

Keywords

  • prostate cancer
  • PSMA
  • dual-modality imaging
  • fluorescence imaging
  • IRDye800CW
  • D2B IgG
  • POSITIVE SURGICAL MARGINS
  • MEMBRANE ANTIGEN
  • RADICAL PROSTATECTOMY
  • EXPRESSION
  • SPECIMENS
  • MODELS
  • TUMORS
  • HEAD

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