Tuesday, November 29, 2022
11/29/2022
Aggressive odontogenic neoplasms, including ameloblastomas, demonstrate locally aggressive and destructive behavior, primarily in the posterior mandible. There are currently no biomarkers or diagnostic strategies for these tumors beyond standard biopsy. This makes it difficult to accurately determine the resection margins, resulting in high rates of residual disease and recurrence. Our long-term goal is to provide non-invasive biomarker-based imaging of ameloblastomas by precisely labeling tumor tissue. This will make it possible to assess tumor margins either pre- or intraoperatively, allowing clinicians to provide better care for their patients. The overarching goal of this proposal is to determine the sensitivity and specificity of a labeled epidermal growth factor receptor (EGFR) antibody, panitumumab, for ameloblastoma tissue and to use it in vivo to image tumor in preclinical models of ameloblastoma. Previously, research on ameloblastoma has been hindered by the lack of in vivo models. To address this gap, in collaboration with oral surgeons, we have developed primary patient-derived xenograft models of ameloblastoma. We demonstrated that fluorescently-labeled anti-EGFR, cetuximab- IRDye800, could specifically identify tumor tissue in vivo. However, it is currently unknown whether fluorescent imaging is sufficient to detect tumor within bone. Two hypothesis-driven specific aims will be investigated as follows: (1) To determine the in vivo sensitivity and specificity of panitumumab-IRDye800 and 89Zr-panitumumab for human ameloblastoma patient-derived xenografts (PDX). We hypothesize that panitumumab-IRDye800 and 89Zr-panitumumab will have higher sensitivity and specificity for ameloblastoma tumor tissue compared to controls. (2) To determine the clinical validity of panitumumab-IRDye800- and 89Zr-panitumumab-based imaging for the surgical removal of tumors using intraosseous models of ameloblastoma. We hypothesize that both panitumumab-IRDye800 and 89Zr-panitumumab will specifically localize to ameloblastomas and allow accurate margin determination and surgical removal of tumors. We utilize a new intraosseous orthotopic animal model and novel imaging probes to non-invasively image, stratify and guide surgical resection in ameloblastomas. PET/CT imaging of novel radiopharmaceutical, 89Zr-panitumumab, provides a three-dimensional preoperative evaluation of tumor location, heterogeneity of EGFR expression, and extension in to the jaw, while panitumumab- IRDye800 provides a corresponding yet complimentary approach for intraoperative margin assessment. The assembled research team is ideal to address for this work in terms of experience, expertise, access and state- of-the-art imaging agents and facilities. This project has the potential to develop a method to accurately image ameloblastomas, and provides a tool for assessing bone invasion in a patient population that is vastly under- represented in the existing research. These imaging strategies will make it possible to non-invasively and accurately image tumors to determine the area of resection in order to obtain clear margins, while also reducing the resection of healthy tissue. Thus, this research has the potential to directly impact patient care.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
