Sensitivity and specificity of fluorescent immunoguided neoplasm detection in head and neck cancer xenografts

Abstract

Objectives: To determine whether fluorescently labeled anti-epidermal growth factor (EGFR) antibody could be used to detect residual disease and to guide surgical resections by comparing the sensitivity and specificity of optical fluorescence imaging with the sensitivity and specificity of histopathologic evaluation.

Design: A preclinical model of head and neck squamous cell carcinoma.

Subjects: Mice xenografted with SCC-1 tumor cells.

Interventions: The mice underwent systemic injection with anti-EGFR antibody (cetuximab) conjugated to an optically active fluorophore (Cy5.5). Both a subcutaneous flank model (n = 18) and an orthotopic murine model (n = 15) were used to assess for the presence of residual disease by fluorescent stereomicroscopy after subtotal resections of tumors. Histologic analysis was performed to confirm the presence or absence of disease.

Results: In the subcutaneous flank model, a diagnostic dose (50 microg) and therapeutic dose (250 microg) of fluorescent-labeled anti-EGFR were administered. When a diagnostic dose was given, the sensitivity was 86%, which was less than the 91% sensitivity when the higher dose was given. Tumor biopsy specimens in which disease was detected by histologic analysis but not by fluorescence (false-negative result) averaged 166 cells (range, 50-350 cells). The specificity of optical fluorescence to predict the presence of tumor in both groups was 100%. In the floor of the mouth model, we demonstrated a sensitivity of 81% and a specificity of 100%. False-negative results were obtained in a tumor fragment measuring less than 0.5 mm in diameter.

Conclusion: These data support further investigation of fluorescently labeled anti-EGFR antibody to detect disease in the surgical setting.