title: Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Antigen specificities and in vitro imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (n = 22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology.
  
  
  RESULTS
  Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (K D = 0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW in vitro. In vivo, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19: p = 0.08 SPY, p = 0.48 Pearl; SCC-1: p = 0.77 SPY, p = 0.59 Pearl; paired t tests).
  
  
  CONCLUSIONS
  There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC.
authors.affiliation: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Volker Hall G082, 1670 University Blvd, Birmingham, AL, 35233, USA.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Day
authors.forename: Larissa
authors.initials: L
authors.lastname: Sweeny
authors.forename: Brian
authors.initials: B
authors.lastname: Kulbersh
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D000077544:Panitumumab; D011485:Protein Binding; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab