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。目前还没有针对这些疾病的生物标志物或诊断策略 超出标准活组织检查的肿瘤。这使得很难准确地确定切除边缘，从而导致 残留率和复发率高。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，临床医生都能为他们的病人提供更好的护理。首要目标是 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 成釉细胞瘤组织的表皮生长因子受体(EGFR)抗体Panitumumab及其用于临床前肿瘤的体内显像 造釉细胞瘤模型。此前，成釉细胞瘤的研究因缺乏体内实验而受到阻碍。 模特们。为了解决这一差距，我们与口腔外科医生合作，开发了初级患者衍生的 成釉细胞瘤异种移植模型的建立。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。然而，目前尚不清楚荧光素是否 成像足以检测到骨骼内的肿瘤。两个假设驱动的具体目标将被调查为 (1)测定Panitumab-IRDye800和89Zr-Panitumab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Panitumab-IRDye800和 对成釉细胞瘤组织的敏感性和特异性较高。 控制。(2)确定Panitumab-IRDye800和89Zr-Panitumumab的临床有效性 用于使用成釉细胞瘤骨内模型的肿瘤手术切除。我们假设两者都是 Panitumumab-IRDye800和89Zr-panitumab将专门定位于成釉细胞瘤并允许准确的 肿瘤的切缘确定和手术切除。我们利用一种新的骨内原位动物模型 以及新型成像探头，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-panitumab的PET/CT成像提供了术前的三维图像 评估肿瘤的位置、EGFR表达的异质性和向颌骨的扩散，而Panitumab- IRDye800为术中保证金评估提供了一种相应而又有益的方法。这个 组建的研究团队在经验、专业知识、访问和状态方面是解决这项工作的理想选择- 最先进的成像剂和设备。这个项目有可能开发出一种精确成像的方法 成釉细胞瘤，并提供了一种工具来评估骨侵犯的患者群体远远低于- 在已有的研究中具有代表性。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，以获得清晰的边缘，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的护理。

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.