title: SPECT- and fluorescence image-guided surgery using a dual-labeled carcinoembryonic antigen-targeting antibody.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands mark.rijpkema@radboudumc.nl.
authors: Mark
authors: M
authors: Rijpkema
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Wim J
authors: WJ
authors: Oyen
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Desiree
authors: D
authors: Bos
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Gerben M
authors: GM
authors: Franssen
authors: Immunomedics, Inc., Morris Plains, New Jersey; and Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, New Jersey.
authors: David M
authors: DM
authors: Goldenberg
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Otto C
authors: OC
authors: Boerman
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000601:surgery*; D005260:Female; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D013050:Spectrometry, Fluorescence; D025321:Surgery, Computer-Assisted / Q000379:methods*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D002272:Carcinoembryonic Antigen; D007205:Indium Radioisotopes
keywords: CEA; MN-14; colorectal cancer; fluorescence imaging; image-guided surgery