Non-Invasive Imaging of Ameloblastomas

侵袭性牙源性肿瘤，包括成釉细胞瘤，表现为局部侵袭性和破坏性 行为，主要是在后下颌骨。目前还没有针对这些疾病的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边缘， 高残留率和复发率。我们的长期目标是提供基于生物标记的非侵入性 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，使临床医生能够为患者提供更好的护理。总体目标 这项建议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， 本发明涉及用于成釉细胞瘤组织的EGFR抗体帕尼单抗，并在体内使用其在临床前研究中对肿瘤进行成像。 造釉细胞瘤模型。以前，对成釉细胞瘤的研究一直受到缺乏体内研究的阻碍。 模型为了解决这一差距，与口腔外科医生合作，我们开发了主要的患者源性 成釉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， IRDye 800可特异性识别体内肿瘤组织。然而，目前尚不清楚荧光是否 成像足以检测骨内的肿瘤。两个假设驱动的具体目标将被调查， （1）确定帕尼单抗-IRDye 800和89 Zr-帕尼单抗的体内敏感性和特异性 用于人成釉细胞瘤患者来源的异种移植物（PDX）。我们假设帕尼单抗-IRDye 800和 89 Zr-帕尼单抗对成釉细胞瘤肿瘤组织的敏感性和特异性高于 对照(2)确定帕尼单抗-IRDye 800和89 Zr-帕尼单抗成像的临床有效性 用于使用成釉细胞瘤的骨内模型手术切除肿瘤。我们假设 帕尼单抗-IRDye 800和89 Zr-帕尼单抗将特异性定位于成釉细胞瘤， 边缘确定和手术切除肿瘤。我们利用一种新的骨内原位动物模型 以及新型成像探针，用于非侵入性成像、分层和引导成釉细胞瘤的手术切除。 新型放射性药物89 Zr-帕尼单抗的PET/CT成像提供了一个三维术前评估。 评价肿瘤位置、EGFR表达的异质性和向颌部的扩展，而帕尼单抗- IRDye 800为术中切缘评估提供了相应的补充方法。的 组装的研究团队是理想的，以解决这项工作的经验，专业知识，访问和状态- 最先进的成像剂和设备。该项目有可能开发一种方法， 成釉细胞瘤，并提供了一种工具，用于评估骨浸润的患者群体，这是大大低于- 在现有的研究中。这些成像策略将使非侵入性和 准确成像肿瘤，以确定切除区域，以获得清晰的边缘，同时还减少 切除健康组织因此，这项研究有可能直接影响患者护理。

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.