title: Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.
abstract: OBJECTIVE
  The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer.
  
  
  METHODS
  Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence.
  
  
  RESULTS
  The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS.
  
  
  CONCLUSIONS
  Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model.
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Metildi
authors.forename: Sharmeela
authors.initials: S
authors.lastname: Kaushal
authors.forename: George A
authors.initials: GA
authors.lastname: Luiken
authors.forename: Mark A
authors.initials: MA
authors.lastname: Talamini
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002232:Carbocyanines; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002678:Chimera; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D003952:Diagnostic Imaging / Q000379:methods*; D005455:Fluorescent Antibody Technique / Q000379:methods*; D005456:Fluorescent Dyes; D064593:Heterografts; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D051379:Mice; D008819:Mice, Nude
chemical_list: C569686:Alexa Fluor 647; D000911:Antibodies, Monoclonal; D002232:Carbocyanines; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes
keywords: chimeric antibody; colon cancer; fluorescence-guided surgery; orthotopic mouse models