IADR Abstract Archives
Fluorescently Labeled Anti-EGFR to Optically Image Ameloblastoma in vivo
Objectives: Introduction: Ameloblastomas demonstrate locally aggressive and destructive behavior, primarily in the posterior mandible. Wide variability in surgical treatment has been advocated leading to residual disease and wide ranges 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 fluorescently labeled anti-EGFR antibody, cetuximab-IRDye800CW, to ameloblastoma tumor cells in vitro and in vivo.
Methods: Methods: Tumor cells were stained with fluorescent cetuximab-IRDye800CW or non-specific IgG-IRDye800CW. 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.
Results: Results: Specific binding of cetuximab-IRDye800CW to ameloblastoma cells was demonstrated by positive staining, with little to no staining seen with the negative control IgG-IRDye800CW. PDX tumor imaging revealed the tumor-to-background ratios (TBRs) produced by cetuximab were significantly higher than those produced by IgG by day 7 and remained significantly higher through day 14 for AB-20. Following skin flap removal to represent a pre-resection state, TBRs increased with cetuximab and were significantly higher than the IgG control for PDX tumors derived from four ameloblastoma patients (AB-20, AB-29, AB-33, AB-34). Excised tissues were paraffin-embedded to confirm the presence of tumor by optical imaging and H&E staining in PDX tumors.
Conclusions: Conclusions: Fluorescently labeled anti-EGFR demonstrates specificity and sensitivity for ameloblastoma cells and PDX tumor xenografts. Next, we are developing a bone-orthotopic model to better represent the ameloblastoma tumor microenvironment and determine the ability to detect tumor within bone. This will give surgeons technology to more confidently remove ameloblastomas by accurately assessing tumor margins to improve long-term local tumor control and reduce recurrence in this patient population.
Objective: The objective is to demonstrate the specificity and sensitivity of fluorescently labeled anti-EGFR antibody, cetuximab-IRDye800CW, to ameloblastoma tumor cells in vitro and in vivo.
Methods: Methods: Tumor cells were stained with fluorescent cetuximab-IRDye800CW or non-specific IgG-IRDye800CW. 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.
Results: Results: Specific binding of cetuximab-IRDye800CW to ameloblastoma cells was demonstrated by positive staining, with little to no staining seen with the negative control IgG-IRDye800CW. PDX tumor imaging revealed the tumor-to-background ratios (TBRs) produced by cetuximab were significantly higher than those produced by IgG by day 7 and remained significantly higher through day 14 for AB-20. Following skin flap removal to represent a pre-resection state, TBRs increased with cetuximab and were significantly higher than the IgG control for PDX tumors derived from four ameloblastoma patients (AB-20, AB-29, AB-33, AB-34). Excised tissues were paraffin-embedded to confirm the presence of tumor by optical imaging and H&E staining in PDX tumors.
Conclusions: Conclusions: Fluorescently labeled anti-EGFR demonstrates specificity and sensitivity for ameloblastoma cells and PDX tumor xenografts. Next, we are developing a bone-orthotopic model to better represent the ameloblastoma tumor microenvironment and determine the ability to detect tumor within bone. This will give surgeons technology to more confidently remove ameloblastomas by accurately assessing tumor margins to improve long-term local tumor control and reduce recurrence in this patient population.