Non-Invasive Imaging of Ameloblastomas

成釉细胞瘤的非侵入性成像

基本信息

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
项目类别：
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

项目摘要

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行为，主要发生在下颌后部。目前尚无针对这些疾病的生物标志物或诊断策略超出标准活检范围的肿瘤。这使得精确确定切除边缘变得困难，残留病和复发率高。我们的长期目标是提供基于非侵入性生物标志物的通过精确标记肿瘤组织对成釉细胞瘤进行成像。这将使评估肿瘤边缘成为可能无论是术前还是术中，临床医生都可以为患者提供更好的护理。总体目标该提案的目的是确定标记的表皮生长因子受体的敏感性和特异性 (EGFR) 抗体帕尼单抗，用于成釉细胞瘤组织并在临床前体内使用它对肿瘤进行成像成釉细胞瘤模型。此前，由于缺乏体内研究，成釉细胞瘤的研究一直受到阻碍。模型。为了解决这一差距，我们与口腔外科医生合作，开发了主要的源自患者的成釉细胞瘤异种移植模型。我们证明荧光标记的抗 EGFR、西妥昔单抗 IRDye800，可以特异性识别体内肿瘤组织。但目前尚不清楚是否有荧光成像足以检测骨内的肿瘤。两个假设驱动的具体目标将被研究为如下： (1) 测定帕尼单抗-IRDye800和89Zr-帕尼单抗的体内敏感性和特异性用于人类成釉细胞瘤患者来源的异种移植物（PDX）。我们假设帕尼单抗-IRDye800 和与 89Zr-panitumumab 相比，89Zr-panitumumab 对成釉细胞瘤肿瘤组织具有更高的敏感性和特异性控制。 (2) 确定基于帕尼单抗-IRDye800和89Zr-帕尼单抗成像的临床有效性用于使用成釉细胞瘤骨内模型进行肿瘤切除手术。我们假设两者帕尼单抗-IRDye800 和 89Zr-帕尼单抗将特异性定位于成釉细胞瘤，并允许准确切缘确定和手术切除肿瘤。我们利用新的骨内原位动物模型以及新型成像探针，用于对成釉细胞瘤进行非侵入性成像、分层和指导手术切除。新型放射性药物 89Zr-panitumumab 的 PET/CT 成像提供了三维术前评估肿瘤位置、EGFR 表达的异质性以及向颌部的延伸，而帕尼单抗- IRDye800 为术中切缘评估提供了相应且互补的方法。这组建的研究团队在经验、专业知识、访问权限和状态方面非常适合完成这项工作最先进的成像剂和设施。该项目有潜力开发一种准确成像的方法成釉细胞瘤，并提供了一种用于评估严重缺乏的患者群体中骨侵袭的工具在现有研究中有所体现。这些成像策略将使非侵入性和准确地对肿瘤进行成像以确定切除区域，以获得清晰的切缘，同时也减少切除健康组织。因此，这项研究有可能直接影响患者护理。