SPECT- and fluorescence image-guided surgery using a dual-labeled carcinoembryonic antigen-targeting antibody

J Nucl Med. 2014 Sep;55(9):1519-24. doi: 10.2967/jnumed.114.142141. Epub 2014 Jun 30.


Intraoperative visualization techniques promise to significantly improve the detection and resection of tumors. In this study, we used an anti-carcinoembryonic antigen (CEA) antibody (MN-14) tagged with both a radiolabel ((111)In) and a fluorophore (IRDye 800CW) for radionuclide detection and intraoperative fluorescence imaging, respectively.

Methods: For this purpose, we prepared and characterized the dual-labeled antibody (111)In-diethylenetriaminepentaacetic acid (DTPA)-MN-14-IRDye 800CW and performed 4 studies on mice with subcutaneous and intraperitoneal CEA-expressing tumors: a dose escalation study to determine the optimal MN-14 protein dose, a biodistribution study comparing dual-labeled MN-14 and radiolabeled MN-14, a study to determine the optimal time for SPECT and fluorescence imaging after injection of dual-labeled MN-14, and finally a SPECT and fluorescence image-guided surgery study using this dual-labeled antibody.

Results: The optimal protein dose of dual-labeled MN-14 was 10 μg per mouse, yielding a tumor-to-blood ratio of 3.5 within 72 h. The biodistribution of (111)In-DTPA-MN-14-IRDye 800CW in mice with subcutaneous LS174T tumors showed tumor uptake after 3 d (19.7% ± 17.0% injected dose/g) comparable to that of (111)In-DTPA-MN-14 but higher accumulation in the liver. The optimal time for imaging after administration of the dual-labeled antibody was 2-3 d after injection. Finally, in mice with intraperitoneally growing LS174T tumor nodules that received (111)In-DTPA-MN-14-IRDye 800CW, intraperitoneal tumor nodules could be localized with SPECT imaging after 3 d and subsequently resected using fluorescence image-guided surgery.

Conclusion: Thus, we showed the feasibility for assessment and image-guided resection of CEA antigen-expressing tumors using dual-labeled MN-14. Both radionuclide detection and fluorescence imaging may provide useful information to improve localization of tumors and radical excision of tumor tissue. Because humanized MN-14 (labetuzumab) is available for clinical use, translation to a clinical setting is the next step.

Keywords: CEA; MN-14; colorectal cancer; fluorescence imaging; image-guided surgery.

MeSH terms

  • Animals
  • Carcinoembryonic Antigen / immunology*
  • Colorectal Neoplasms / surgery*
  • Female
  • Indium Radioisotopes*
  • Mice
  • Mice, Inbred BALB C
  • Spectrometry, Fluorescence
  • Surgery, Computer-Assisted / methods*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods*


  • Carcinoembryonic Antigen
  • Indium Radioisotopes