Effective fluorescence-guided surgery of liver metastasis using a fluorescent anti-CEA antibody

J Surg Oncol. 2016 Dec;114(8):951-958. doi: 10.1002/jso.24462. Epub 2016 Oct 3.

Abstract

Background and objectives: Delineation of adequate tumor margins is critical in oncologic surgery, particularly in resection of metastatic lesions. Surgeons are limited in visualization with bright-light surgery, but fluorescence-guided surgery (FGS) has been efficacious in helping the surgeon achieve negative margins.

Methods: The present study uses FGS in a mouse model that has undergone surgical orthotopic implantation (SOI) of colorectal liver metastasis tagged with green fluorescent protein (GFP). An anti-CEA antibody conjugated to DyLight 650 was used to highlight the tumor.

Results: The fluorescent antibody clearly demarcated the lesion at deeper tissue depth compared to GFP. Fluorescence of the anti-CEA-DyLight650 showed maximal tumor-to-liver contrast at 72 hr. Fifteen mice underwent bright-light surgery (BLS) versus FGS with GFP versus FGS with anti-CEA-DyLight650. Mice that underwent FGS had a significantly smaller area of residual tumor (P < 0.001) and significantly longer overall survival (P < 0.001) and disease-free survival (P < 0.001). Within the two FGS groups, mice undergoing surgery with anti-CEA-DyLight650 improved survival compared to only GFP labeling.

Conclusions: In the present report, we demonstrate that an anti-CEA antibody conjugated to a DyLight 650 nm dye clearly labeled colon cancer liver metastases, thereby enabling successful FGS. J. Surg. Oncol. 2016;114:951-958. © 2016 Wiley Periodicals, Inc.

Keywords: colon-cancer liver metastasis; disease-free survival; fluorescence-guided surgery; fluorescent anti-CEA antibody; orthotopic-liver metastasis model; survival.

MeSH terms

  • Animals
  • Antibodies, Monoclonal*
  • Carcinoembryonic Antigen / immunology*
  • Colorectal Neoplasms / pathology
  • Fluorescent Antibody Technique, Direct
  • Fluorescent Dyes*
  • HT29 Cells
  • Hepatectomy / methods*
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Optical Imaging / methods*
  • Random Allocation
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Fluorescent Dyes