Assessment of Hypoxia in Malignant Gliomas Using EF5

描述：(申请人提供)自20世纪50年代以来，人们就知道 低氧肿瘤细胞需要高达3倍的辐射剂量 好氧细胞的毒性相同。因为受到的总辐射剂量 受限于正常邻近组织的耐受性，寻找 克服“缺氧问题”的方法主导了辐射生物学 过去半个世纪的研究。攻击的主要限制之一是 这个问题是无法识别和量化存在的 个别患者体内的低氧细胞。在过去的十年中，可获得的 埃彭多夫针状电极技术使数据能够在 患者肿瘤组织的氧合作用。这类研究已经证明了低氧对 对子宫颈癌、肉瘤和头颈癌的预后有负面影响。 也有大量证据表明，缺氧是存在的，而且是生物学上的。 与恶性脑瘤有关。我们临床缺氧的总体目标是 计划是确定EF5的存在、水平和模式 结合作用对癌症患者的预后和治疗反应具有重要意义。 我们的兴趣包括肉瘤患者，头颈部鳞癌患者， 子宫颈癌，现在，又有脑瘤患者。在建议的研究中 在这里，我们将研究幕上新生患者的EF5结合情况。 恶性胶质瘤(SMG)。在同一患者组中使用 埃彭多夫针电极将成为通向之前发表的工作的桥梁。 我们将确定EF5结合与临床结果的关系 多形性胶质母细胞瘤(GBM)与非GBM组织学对照。至 为了更好地了解MG的病理生理机制，我们将研究MG的存在和 各种附加生物标志物的水平。这些研究是必要的 脑肿瘤缺氧的非侵入性研究的初步研究。 这些非侵入性研究将基于正电子发射断层扫描(PET) 对18F-EF5进行成像，然后进行低氧特异性治疗干预。 本课题组已经合成了18F-EF5，并对其在动物肿瘤中的作用进行了研究。这个 必要的额外临床前研究和许可证申请 宾夕法尼亚大学(宾夕法尼亚大学)正在进行这些PET研究。我们 我们将能够在宾夕法尼亚大学进行临床EF5 PET研究的项目 脑肿瘤患者在大约2年内，对应的时间 这里提出的研究中的许多数据将会成熟。

DESCRIPTION: (Provided by applicant) It has been known since the 1950s that hypoxic tumor cells require up to 3 times the radiation dose compared to aerobic cells for equal toxicity. Because the total radiation dose administered is limited by the tolerance of normal adjacent tissues, the search for approaches to overcome the "hypoxia problem" has dominated radiation biology research for the last half century. One of the major limitations to attacking this problem has been the inability to identify and quantitate the presence of hypoxic cells in individual patients. In the last decade, the availability of the Eppendorf needle electrode technology has allowed data to be obtained on tumor tissue oxygenation in patients. Such studies have demonstrated hypoxia to negatively influence outcome in cervix, sarcomas and head and neck cancers. There is also substantial evidence that hypoxia exists and is biologically relevant in malignant brain tumors. The overall goal of our clinical hypoxia program is to determine whether the presence, levels and patterns of EF5 binding are important in the prognosis and therapy response of cancer patients. Our interests include patients with sarcomas, head and neck squamous cancer, cervix cancer and now, patients with brain tumors. In the studies proposed herein, we will study EF5 binding in patients with de novo supratentorial malignant gliomas (SMG). Concurrent studies in the same patient group using the Eppendorf needle electrode will serve as a bridge to previously published work. We will determine the relationship between EF5 binding and clinical outcome in patients with glioblastoma multiforme (GBM) versus non-GBM histologies. To better understand the pathophysiology of MG, we will study the presence and levels of various additional biomarkers. These studies are the necessary preliminary studies towards non-invasive studies of hypoxia in brain tumors. These non-invasive studies will be based on Positron Emission Tomographic (PET) imaging of 18F-EF5 followed by hypoxia-specific treatment interventions. 18F-EF5 has been synthesized and studied in animal tumors by our group. The necessary additional pre-clinical studies and applications for permits for these PET studies are ongoing at the University of Pennsylvania (PENN). We project that we will be able to institute clinical EF5 PET studies at PENN in patients with brain tumors in approximately 2 years, corresponding to the time that much of the data from the studies proposed herein will mature.