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.

侵略性的牙源性肿瘤，包括蛋白母细胞瘤，表现出局部侵略性和破坏性行为，主要是在后颌骨中。目前没有生物标志物或诊断策略超出标准活检的肿瘤。这使得难以准确确定切除率，从而在残留疾病和复发的高率中。我们的长期目标是提供非侵入性生物标志物通过精确标记肿瘤组织来对绿细胞瘤进行成像。这将使评估肿瘤边缘成为可能术前或术中，允许临床医生为患者提供更好的护理。总体目标该建议的是确定标记表皮生长因子受体的灵敏度和特异性（EGFR）抗体，panitumumab，用于蛋白母细胞瘤组织，并在体内使用它来对临床前的肿瘤进行图像图像绿细胞瘤的模型。以前，缺乏体内的蛋白母细胞瘤的研究受到了阻碍型号。为了解决这一差距，与口腔外科医生合作，我们开发了主要的患者衍生绿细胞瘤的异种移植模型。我们证明了荧光标记的抗EGFR，西妥昔单抗 - IRDYE800可以在体内特异性地识别肿瘤组织。但是，目前尚不清楚荧光是否成像足以检测骨骼内的肿瘤。两个假设驱动的特定目标将被研究为以下内容：（1）确定panitumumab-ryye800和89zr-panitumumab的体内灵敏度和特异性用于人熟母细胞瘤患者衍生的异种移植物（PDX）。我们假设panitumumab-righye800和 89ZR-Panitumumab对绿细胞瘤肿瘤组织具有更高的敏感性和特异性控件。（2）确定panitumumab-ryye800和89zr-panitumumab的临床有效性用于使用片内模型的绿细胞瘤模型进行外科手术去除。我们假设这两个 panitumumab-rirdye800和89zr-Panitumumab将专门定位于蛋白母细胞瘤，并允许准确边缘测定和手术切除肿瘤。我们利用新的骨内矫形动物模型以及新的成像探针以非侵入性图像，对木质母细胞瘤中的手术切除进行分层和指导手术切除。新型放射性药物的PET/CT成像89ZR-Panitumumab提供了三维术前肿瘤位置的评估，EGFR表达的异质性以及向下颌延伸，而Panitumumab- IRDYE800提供了术中边缘评估的相应但免费的方法。这组装研究团队是在经验，专业知识，访问和州 - 艺术成像代理和设施。该项目有可能开发一种准确图像的方法 ameloblastomas，并提供了一种评估骨入侵的工具在现有研究中代表。这些成像策略将使无创和准确地对肿瘤进行图像以确定切除面积以获得清晰的边缘，同时还会减少健康组织的切除。因此，这项研究有可能直接影响患者护理。