Preclinical Comparison of Near-Infrared-Labeled Cetuximab and Panitumumab for Optical Imaging of Head and Neck Squamous Cell Carcinoma

Mol Imaging Biol. 2013 Dec;15(6):722-9. doi: 10.1007/s11307-013-0652-9.

Abstract

Purpose: 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).

Procedures: 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cetuximab
  • ErbB Receptors / analysis
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Mice
  • Optical Imaging / methods*
  • Panitumumab
  • Protein Binding
  • Spectroscopy, Near-Infrared / methods*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Fluorescent Dyes
  • Panitumumab
  • ErbB Receptors
  • Cetuximab