Project 3: Direct & Repeated Measurement of pO2 in Deep-seated Tumors using EPR O

项目3：直接

• 批准号: 8795077
• 负责人: HAROLD M SWARTZ
• 金额: $ 22.7万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8795077
• 关键词: Air; Angiogenesis Inhibitors; Animal Model; Avastin; Brain; Brain Neoplasms; Breathing; Carbogen; Carbogen Breathing; Carbon; Carbon Dioxide; Charcoal; Clinic; Clinical; Clinical Data; Clinical Trials; Communities; Data; Development; Diagnostic; Direct Repeats; Effectiveness; Encapsulated; Evolution; Excision; Experimental Animal Model; Feasibility Studies; Future; Gases; Glioma; Goals; Head and Neck Neoplasms; Head and Neck Squamous Cell Carcinoma; Head and Neck Surgery; Head and neck structure; Histologic; Human; Hyperbaric Oxygenation; Hypoxia; Implantation procedure; India ink stain; Individual; Intervention; Knowledge; Lithium; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Metastatic malignant neoplasm to brain; Monitor; Neoplasm Metastasis; Outcome; Oxygen; Oxygen saturation measurement; Pathology; Patients; Primary Brain Neoplasms; Procedures; Radiation; Radiation Oncology; Radiation therapy; Recurrence; Role; Safety; Site; Skin; Specialist; Surface; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Translations; Treatment outcome; Variant; antiangiogenesis therapy; bench to bedside; biocompatible polymer; biomaterial compatibility; cancer therapy; chemotherapy; clinical application; design; implantation; improved; instrument; meetings; microwave electromagnetic radiation; neurosurgery; novel; particle; pre-clinical; preclinical study; prognostic; response; safety study; sarcoma; sensor; soft tissue; therapeutic angiogenesis; therapy resistant; treatment planning; treatment response; tumor

A number of strategies to improve oxygen levels in tumors by oxygen enriched gases or modulation of tumor vasculature (e.g. ARCON, avastin) have failed to show efficacy in clinical trials despite promising pre-clinical results. A major caveat in these studies is the lack of techniques for monitoring oxygen levels in the tumors and therefore it is not known if the therapy indeed was effective in reducing tumor hypoxia. It is imperative to monitor tumor pO2 to understand treatment responses in future clinical trials. In project 3, we will implement a novel implantable deep-tissue oxygen sensor approach with improved versatility to be used in tumors located at depths > 10 mm from the patient's skin. This approach will use OxyChip (Project 2), but with the addition of a thin (<0.2 mm wire gauge) non-magnetic wire to transduce the microwave energy from deep-tissue to the spectrometer for the acquisition of EPR spectra. The implantable deep-tissue oxygen sensors has been designed and rigorously tested for pO2 measurements at 2-4 sites simultaneously, MRI compatibility, and biocompatibility in experimental animal models. We will first perform a safety and feasibility study in patients, and then proceed with a two institutional (Dartmouth and Emory) study to measure oxygen levels at baseline, temporal fluctuations and response to hyperoxygenation with carbogen (2% CO2 + 98% O2) breathing. Importantly, we will measure oxygen levels in recurrent gliomas being treated with an anti-angiogenic agent, avastin. This study will contribute to our understanding of the effect of avastin on tumor pO2 in patients and determine how best to administer avastin with radiation therapy for improving treatment outcomes. These studies will provide a paradigm to measure tumor oxygen levels during therapy and will be the first step in disseminating this technology to the broader radiation oncology community. We propose the following specific aims to meet the objective of this project and the overall goals of the PPG: (1) Establish the efficacy and safety of implantable deep-tissue oxygen sensors and investigate pre-treatment oxygen profiles of patients with deep-seated head and neck, sarcoma and brain tumors; (2) Determine the response and change in pO2 induced by hyperoxygenation and anti-angiogenic treatment in human tumors, and (3) Determine tumor oxygen levels during concurrent treatment with radiation and subsequently evaluate the effects of oxygen-modifying interventions during radiotherapy. Project 3 will fulfill the unmet need for monitoring pO2 in deep-seated tumors, which will provide clinicians crucial diagnostic, therapeutic, and prognostic information to improve the treatment outcome of patients.

通过富含氧气的气体或调节肿瘤来改善肿瘤中氧气水平的许多策略 尽管有希望的临床前，脉管系统（例如Arcon，Avastin）在临床试验中仍未显示功效 结果。这些研究中的一个主要警告是缺乏监测肿瘤和氧气水平的技术 因此，尚不清楚该治疗是否确实有效减少肿瘤缺氧。必须监视 在将来的临床试验中了解治疗反应的肿瘤PO2。 在项目3中，我们将实施一种新型的可植入深的组织氧气传感器方法，并具有改善的多功能性 用于距离患者皮肤大于10毫米的深度肿瘤。这种方法将使用Oxychip（项目 2），但加上薄（<0.2 mm的电线量规）非磁性线来传输微波炉 从深度组织到光谱仪，以获取EPR光谱。可植入的深组织氧气 传感器已经过设计和严格测试，以同时在2-4个位点进行PO2测量，MRI 实验动物模型中的兼容性和生物相容性。我们将首先执行安全性和可行性 对患者进行研究，然后进行两项机​​构（达特茅斯和埃默里）研究以测量氧气 基线时的水平，时间波动和对碳原质高氧化的反应（2％CO2 + 98％O2） 呼吸。重要的是，我们将测量用抗血管生成治疗的复发性神经胶质瘤中的氧气水平 特工，阿瓦斯汀。这项研究将有助于我们理解阿伐他蛋白对肿瘤PO2的影响 并确定如何通过放射疗法最好地施用阿瓦斯汀来改善治疗结果。这些 研究将提供一个范式来测量治疗期间肿瘤氧的水平，将是第一步 将这项技术传播到更广泛的辐射肿瘤学界。 我们提出以下具体目标，以实现该项目的目标以及PPG的总体目标： （1）建立可植入深的组织氧气传感器的功效和安全性并研究预处理 头颈部和颈部，肉瘤和脑肿瘤患者的氧气谱； （2）确定 人类肿瘤中高氧和抗血管生成治疗引起的PO2的反应和变化， （3）确定在辐射的并发处理过程中的肿瘤氧水平，然后评估 放疗过程中氧气改良干预措施的影响。项目3将满足未满足的需求 监测深座肿瘤中的PO2，这将为临床医生提供关键的诊断，治疗和 预后信息以改善患者的治疗结果。