Project 1: Direct & Repeated pO2 Measurements for Cancer using EPR with Carbon Pa

项目1：直接

• 批准号: 9306080
• 负责人: PERIANNAN KUPPUSAMY
• 金额: $ 47.64万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9306080
• 关键词: Address; Adverse effects; Biological Markers; Blood; Breast; Breathing; Cancer Patient; Carbogen Breathing; Carbon; Cervical; Cervical Squamous Cell Carcinoma; Cervix Neoplasms; Charcoal; Clinic; Clinical; Clinical Research; Common Neoplasm; Continuance of life; Cutaneous; Cutaneous Lymphoma; Data; Development; Direct Repeats; Ensure; Fibrosis; Foundations; Goals; Head Cancer; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Hyperbaric Oxygenation; Hypoxia; Imaging Techniques; Imaging technology; Incidence; India ink stain; Individual; Intervention; Knowledge; Lipids; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measurement; Measures; Methods; Modality; Monitor; Neck Cancer; Nitroimidazoles; Normal tissue morphology; Outcome; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Particulate; Patient Selection; Patients; Perfusion; Positron-Emission Tomography; Prognostic Marker; Protocols documentation; Radiation; Radiation Fibrosis; Radiation therapy; Site; Skin; Surface; T-Cell Lymphoma; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Tracer; Treatment Efficacy; Treatment outcome; Tumor Oxygenation; Tumor Pathology; Tumor Tissue; Ultrasonography; Validation; Variant; base; cancer therapy; chemoradiation; chemotherapy; clinical decision-making; clinical practice; head and neck cancer patient; hemodynamics; human subject; imaging modality; improved; irradiation; malignant breast neoplasm; novel; preclinical development; response; sensor; time use; treatment response; tumor; tumor growth

Squamous cell carcinomas of the cervix and head and neck regions are commonly treated with definitive chemoradiotherapy. It is well established that when these tumors are hypoxic, they are much less sensitive to treatments and outcomes are poor, yet there is no method in clinical practice to determine tumor oxygen levels. Of all hypoxia imaging technologies in pre-clinical development, only EPR oximetry has the potential to be used in the clinic, on a daily basis, to measure tumor oxygen levels and to ensure that each and every fraction of radiation therapy is delivered during optimal tumor oxygenation. Importantly, there are other tumor types, such as cutaneous lymphomas, where very little is known about tumor oxygen status. We have preliminary measurements indicating that these tumors can be hypoxic and tumor oxygen levels can be elevated by carbogen breathing. In project 1, we will initiate the first multi-institutional trials to measure tumor oxygen levels over time using EPR oximetry with carbon based oxygen sensors. We will evaluate baseline fluctuations in tumor oxygen levels, the response to carbogen breathing and changes over time due to tumor growth or treatment response. These studies will provide the foundation for more advanced EPR technologies that will be introduced in the later projects. Finally, we will determine if and when normal tissue becomes hypoxic during the development of post-radiation fibrosis, which is an important survivorship issue for breast and head and neck cancer patients. We propose the following specific aims to meet the objective of this project and the overall goals of the PPG: (1) To characterize pO2 values and their temporal (in minutes to weeks) fluctuations in tumors in patients with HNSCC, cervical SCC, or CTCL. (2) To determine the response and change in pO2 induced by hyperoxygenation treatments in head and neck and cervical SCC and CTCL tumors. (3) To compare pO2 values, their temporal variation, and response to hyperoxygenation with currently used hypoxia imaging methods in head and neck and cervical cancer patients. (4) To monitor pO2 dynamics in cervical, head and neck, and CTCL tumors during and following a course of radiation therapy. (5) To monitor pO2 dynamics in radiation-induced fibrosis in breast and head and neck cancer patients who have undergone radiation therapy.

子宫颈和头颈部鳞状细胞癌通常采用以下方法治疗： 明确的放化疗。众所周知，当这些肿瘤缺氧时，它们 对治疗的敏感性较差，效果较差，但临床上尚无方法 练习确定肿瘤的氧水平。所有临床前缺氧成像技术 的发展，只有 EPR 血氧测定法有潜力在临床上每天使用，以 测量肿瘤的氧水平并确保放射治疗的每一个部分都是 在最佳肿瘤氧合期间输送。重要的是，还有其他肿瘤类型，例如 皮肤淋巴瘤，人们对肿瘤的氧状态知之甚少。我们有 初步测量表明这些肿瘤可能缺氧并且肿瘤的氧水平 可以通过卡波根呼吸来升高。在项目1中，我们将启动第一个多机构 使用碳基氧 EPR 血氧测定法测量肿瘤氧水平随时间变化的试验 传感器。我们将评估肿瘤氧水平的基线波动、对肿瘤的反应 由于肿瘤生长或治疗反应，卡波金呼吸会随着时间的推移而变化。这些 研究将为即将推出的更先进的 EPR 技术奠定基础 在后来的项目中。最后，我们将确定正常组织是否以及何时缺氧 在放射后纤维化的发展过程中，这是一个重要的生存问题 乳腺癌和头颈癌患者。为实现以下目标，我们提出以下具体目标： 该项目的目标和 PPG 的总体目标： (1) 表征 pO2 值和 头颈部鳞状细胞癌、宫颈癌患者肿瘤的时间（分钟到周）波动 SCC，或 CTCL。 (2) 测定高氧合引起的pO2反应和变化 头颈和宫颈 SCC 和 CTCL 肿瘤的治疗。 (3) 比较 pO2 值， 它们的时间变化以及当前使用的缺氧成像对高氧合的反应 头颈癌和宫颈癌患者的方法。 (4) 监测 pO2 动态 放射治疗期间和放射治疗后的宫颈癌、头颈部肿瘤和 CTCL 肿瘤。 (5) 监测乳腺癌和头颈癌辐射诱导纤维化的 pO2 动态 接受过放射治疗的患者。