title: Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer.
abstract: OBJECTIVE
  Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer.
  
  
  METHODS
  A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology.
  
  
  RESULTS
  There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels.
  
  
  CONCLUSIONS
  We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology.
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. erosenthal@uabmc.edu.
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Warram
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: de Boer
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Chung
authors.affiliation: Division of General Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Korb
authors.affiliation: Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Margie
authors.initials: M
authors.lastname: Brandwein-Gensler
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Theresa V
authors.initials: TV
authors.lastname: Strong
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Cecelia E
authors.initials: CE
authors.lastname: Schmalbach
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Morlandt
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Garima
authors.initials: G
authors.lastname: Agarwal
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Yolanda E
authors.initials: YE
authors.lastname: Hartman
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: William R
authors.initials: WR
authors.lastname: Carroll
authors.affiliation: Division of General Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Richman
authors.affiliation: Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Clemons
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Lisle M
authors.initials: LM
authors.lastname: Nabell
authors.affiliation: Division of Advanced Medical Imaging, Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D000068818:Cetuximab / Q000008:administration & dosage* / Q000009:adverse effects; D066246:ErbB Receptors; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D061848:Optical Imaging; D011859:Radiography; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; C427728:IRDye800; D007211:Indoles; D066246:ErbB Receptors; D000068818:Cetuximab