Preclinical Comparison of Near-Infrared-Labeled Cetuximab and Panitumumab for Optical Imaging of Head and Neck Squamous Cell Carcinoma
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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).
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.
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).
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.
Key wordsAerodigestive squamous cell carcinoma Head and neck Near-infrared imaging Epidermal growth factor receptor
The authors would like to thank Yolanda Hartman for running the rEGFR assay and Dr. Andra Frost for assistance in pathologic examination of tissue samples.
Conflict of interest
The authors have no financial disclosures or conflicts of interest.
- 5.Keereweer S, Mieog JS, Mol IM, et al. (2011) Detection of oral squamous cell carcinoma and cervical lymph node metastasis using activatable near-infrared fluorescence agents. Archives of otolaryngology--head & neck surgery 137:609–615.Google Scholar
- 33.Leung K (2004) BODIPY-FL-neutravidin-biotin-Cetuximab. In Molecular Imaging and Contrast Agent Database (MICAD). National Center for Biotechnology Information, Bethesda.Google Scholar
- 34.Biosciences L-C (2007) IRDye(R) 800CW Protein Labeling Kit–High MW. Lincoln, LI-COR Biosciences, pp 1–9Google Scholar
- 54.Calabi F, Neuberger MS (1987) Molecular genetics of immunoglobulin. Elsevier, AmsterdamGoogle Scholar