Non-Invasive Imaging of Ameloblastomas

成釉细胞瘤的非侵入性成像

• 批准号: 10424570
• 负责人: Hope Amm
• 金额: $ 18.11万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10424570
• 关键词: 3-Dimensional; Address; Adenoid Cystic Carcinoma; Ameloblastoma; Animal Model; Animals; Antibodies; Area; Behavior; Biodistribution; Biological Markers; Biopsy; Bone neoplasms; Caring; Cells; Cetuximab; Clinical; Collaborations; Decalcification; Development; Devices; Diagnosis; Emission-Computed Tomography; Environment; Epidermal Growth Factor Receptor; Evaluation; Excision; Fc Receptor; Fluorescence; Frozen Sections; Future; Goals; Head and Neck Neoplasms; Heterogeneity; Histology; Human; Image; Image-Guided Surgery; Immunoglobulin G; Implant; Invaded; Investigation; Jaw; Label; Lead; Life; Location; Mandible; Methods; Modeling; Mouth Neoplasms; Mus; Odontogenic Tumors; Operative Surgical Procedures; Oral Surgeon; PET/CT scan; Patient Care; Patient Recruitments; Patient-Focused Outcomes; Patients; Positron-Emission Tomography; Pre-Clinical Model; Radiolabeled; Radiopharmaceuticals; Recurrence; Recurrent disease; Research; Resected; Residual Tumors; Risk; Scanning; Sensitivity and Specificity; Signal Transduction; Specimen; Surgeon; Technology; Tissues; Tumor Tissue; Visual; Work; X-Ray Computed Tomography; base; bone; bone invasion; cancer imaging; cancer type; clinically relevant; diagnostic strategy; experience; fluorescence imaging; imaging agent; imaging biomarker; imaging facilities; imaging probe; improved; in vivo; in vivo Model; innovation; non-invasive imaging; novel; panitumumab; patient derived xenograft model; patient population; preclinical imaging; preservation; receptor expression; soft tissue; targeted agent; targeted imaging; tibia; tool; tumor; uptake

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.

侵袭性牙源性肿瘤，包括成釉细胞瘤，表现出局部侵袭性和破坏性