Ameloblastoma Imaging In Vivo With Intraoperative Fluorescent Detection

Objectives: Ameloblastomas demonstrate locally aggressive and destructive behavior, primarily in the posterior mandible. Wide variability in the efficacy of surgical treatment options has resulted in residual disease and a vast range of disease recurrence (3-62%). It has been previously demonstrated that fluorescently labeled epidermal growth factor receptor (EGFR) antibodies can successfully identify microscopic tumors in multiple in vivo preclinical models of human cancers with limited toxicity.
Objective: The objective is to demonstrate the specificity and sensitivity of a fluorescently labeled anti-EGFR antibody, cetuximab-IRDye800CW, to ameloblastoma tumors in vivo using the LUNA FLI device; an open-field, intraoperative optical imaging device.
Methods: Patient-derived xenografts (PDX) of ameloblastoma were implanted subcutaneously into the flanks of immunocompromised mice and were imaged following tail vein injection of cetuximab-IRDye800CW or IgG-IRDye800CW to label tumor cells.
Results: PDX tumor imaging revealed the tumor-to-background ratios (TBRs) produced by cetuximab were significantly higher than those produced by IgG. Following skin flap removal to represent a pre-resection state, TBRs with cetuximab were significantly higher than the IgG control for PDX tumors derived from three ameloblastoma patients (AB-20 and AB-34, p < 0.01; AB-33, p < 0.05, respectively). Excised PDX tissues were paraffin-embedded to confirm the presence of tumor by optical imaging and H&E staining. EGFR expression was confirmed by immunohistochemistry.
Conclusions: Fluorescently labeled anti-EGFR demonstrates specificity and sensitivity for PDX tumor xenografts using an open-field, near-infrared imaging system. This approach would allow real-time assessment of fluorescent signal during surgical removal of tumors. Surgeons would be able to more confidently remove ameloblastomas by accurately assessing tumor margins to improve long-term local tumor control and reduce recurrence in this patient population.