title: Effective fluorescence-guided surgery of liver metastasis using a fluorescent anti-CEA antibody.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.|AntiCancer, Inc., San Diego, California.|Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.|AntiCancer, Inc., San Diego, California.
authors.forename: Thinzar M
authors.initials: TM
authors.lastname: Lwin
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.|AntiCancer, Inc., San Diego, California.|Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.|AntiCancer, Inc., San Diego, California.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Mawy
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Tanaka
authors.initials: T
authors.lastname: Kuniya
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Clary
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.|AntiCancer, Inc., San Diego, California.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes; D019073:HT29 Cells; D006498:Hepatectomy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary* / Q000601:surgery*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D061848:Optical Imaging / Q000379:methods*; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes
keywords: colon-cancer liver metastasis; disease-free survival; fluorescence-guided surgery; fluorescent anti-CEA antibody; orthotopic-liver metastasis model; survival