Imaging Cutaneous Head and Neck Cancer with Panitumumab-IRDye

Abstract

Objective: To determine if intraoperative, real-time fluorescence imaging hardware (SPY System, Novadaq, Toronto, Canada) and lab-based fluorescence optical imaging of histological sections (Odyssey scanner, LiCor) are capable of detecting micrometastatic cutaneous squamous cell carcinoma (SCC) in preclinical models.

Method: An NIR fluorescent probe (IRDye800) was covalently linked to a monoclonal antibody targeting EGFR (panitumumab) or non-specific IgG and injected into mice bearing flank xenografts derived from a cutaneous SCC cell line (SCC-13). The primary tumor and regional lymph nodes were imaged and dissected using fluorescence guidance with the SPY system and verified with a charge-coupled NIR system (Pearl). An NIR charged-coupled device (Odyssey) was used to measure fluorescence intensity of cut sections of tumor and were confirmed with immunohistochemical staining (cytokeratin, CD147).

Results: Tumors were clearly delineated from normal tissue with tumor-to-background ratios of 4.5 (Pearl) and 3.4 (SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P < .05). Tissue biopsies positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n = 10/10); while biopsies of non-fluorescent tissue were proven to be negative for malignancy (n = 12/12). The SPY system was able to detect regional lymph node metastasis (<1.0 mm) and microscopic areas of disease as small as 200 micrometers in diameter. Additionally, the Odyssey successfully detected residual microscopic disease in both frozen and paraffin-embedded histologic specimens.

Conclusion: These data suggest that panitumumab-IRDye800 may have clinical utility in detection and removal of cutaneous SCC using existing optical imaging hardware. This technique may prove useful in the detection of microscopic disease grossly and in histological sections.