A peptide targeted fluorescence probe for precision surgery of head and neck cancer

Abstract: The goal of this SBIR project is to develop and commercialize a targeted fluorescence dye for intraoperative fluorescence imaging and precision surgical treatment of head and neck cancer (HNC). Surgical resection followed by adjuvant chemotherapy or radiation is a routine therapeutic strategy for HNC, yet locoregional recurrences occur in up to 30% of patients due in part to minimal residual disease in the local tissues. Furthermore, many HNC patients undergo neck dissection procedures to remove lymph nodes at-risk of or containing metastatic tumor nodules, but up to 30% of patients exhibit occult metastases that remain undetected until the disease has progressed. Both of these surgical strategies are highly invasive, extracting wide surgical margins around solid tumors and regularly affecting or removing functional tissue structures, making post-treatment patient quality of life a significant clinical problem. Thus, a clinical challenge for complete tumor resection during primary and metastatic HNC surgeries is highly sensitive detection of small tumors and accurate delineation of tumor margins during surgical operations. Although some targeted fluorescence probes are undergoing clinical development for HNC, most exhibit large chemical structures, which requires them to be injected several hours to days prior to surgery, and target cell surface markers, which are not always tumor-specific and exhibit highly heterogeneous and dynamic expression. We hypothesize that a small fluorescently-labeled peptide specific to an oncoprotein in the tumor extracellular matrix (ECM) can be used to visualize and guide complete resection of HNC. To test this hypothesis, we propose to synthesize and characterize a small peptide-targeted fluorescence dye specific to the ECM oncoprotein in Aim 1, and to determine its specificity and effectiveness for visualization and tumor margin assessment of HNC in animal models in Aim 2. The targeted fluorescence dye can be intravenously injected or applied topically to fluorescently stain HNC tumors to assist surgeons in identify tumors and defining tumor boundaries for complete resection of tumor tissues. After successful demonstration of the feasibility of the targeted imaging probe in this Phase I SBIR project, further preclinical investigations and development will be performed in Phase II for clinical translation and commercialization of the dye for image-guided surgery of HNC.