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

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 (KD=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.

Laparoscopic Fluorescent Visualization of the Ureter With Intravenous IRDye800CW

“…With emissions in the 700 – 900 nm range, NIR avoids interference with auto-fluorescence of other tissues and can penetrate approximately 1 cm of tissue. 19,20 The NIR dye, IRDye800CW-CA, (LI-COR Biosciences) is a modified version of the hepatically-cleared IRDye800CW NHS-Ester that has been studied in animal models and is currently being used in multiple clinical trials 21–23 (clinicaltrials.gov, identifiers NCT01987375, NCT0197273, NCT01508572, NCT02113202, NCT02129933). To facilitate urinary tract imaging, however, IRDye800CW-CA contains a carboxylate group that is excreted renally.…”

Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC

“…In other orthotopic models described in the literature, cell injection may induce dissemination of cancer cells by the hydrostatic pressure from the syringe during injection, resulting in the rapid development of large tumors, requiring sacrifice and thus making it difficult for lymph-node metastasis to develop [7][8][9]. In certain orthotopic animal HNSCC models using cell injection, the cervical lymph-node metastases that did develop may have been due to cell dissemination by hydrostatic pressure in the lymph vessels during injection rather than to cell migration from the primary site [9,10]. Such models thus fail to reproduce the reality of the lymph-node metastasis process.…”

Imaging in animal models

“…Near infrared fluorescence imaging is being developed in order to overcome these limitations by focusing on the detection of exogenously administered contrast agents that emit fluorescence between 700-900 nm [26]. Recent animal studies have shown promising uses of near-infrared fluorescence imaging for the demarcation of subcutaneous and orthotopic xenograph tumours during surgery [27][28][29]. Resection of the tumours was carried out under guidance of near-infrared fluorescence imaging, enabling identification of any remaining cancerous cells in situ [30].…”