Project 2: Direct & Repeated pO2 Measurements for Cancer using EPR Oximetry with

项目2：直接

• 批准号: 8795076
• 负责人: PERIANNAN KUPPUSAMY
• 金额: $ 16.06万
• 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/8795076
• 关键词: Address; Aftercare; Animal Model; Breast Cancer Patient; Cancer Patient; Carbon; Clinical; Clinical Trials; Data; Devices; Direct Repeats; ERBB2 gene; Encapsulated; FDA approved; Goals; Human; Hyperbaric Oxygenation; Hypoxia; Implantation procedure; Individual; Intervention; Knowledge; Lithium; Malignant - descriptor; Malignant Neoplasms; Measurement; Measures; Methods; Monitor; Neoadjuvant Therapy; Neoplasm Metastasis; Noise; Normal tissue morphology; Operative Surgical Procedures; Outcome; Oxygen; Oxygen Therapy Care; Oxygen saturation measurement; Particulate; Patients; Radiation; Radiation therapy; Recurrence; Research Design; Safety; Sampling; Signal Transduction; Site; Surface; Surgical complication; Systemic Therapy; Testing; Therapeutic; Time; Tissues; Translations; Trastuzumab; Tumor Oxygenation; Variant; Work; abstracting; base; biocompatible polymer; cancer therapy; chemotherapy; clinically relevant; effective therapy; human subject; improved; innovation; malignant breast neoplasm; meetings; new technology; novel; polydimethylsiloxane; pre-clinical; radiation response; research study; response; sensor; tissue oxygenation; tool; treatment planning; tumor

Abstract Hypoxia is a common feature in many human tumors. Hypoxia causes increased malignant potential including metastasis and higher rate of recurrence. Most importantly, hypoxia impairs tumor response to radiation and certain chemotherapy. Therefore, considerable effort has been focused on improving the oxygen content of hypoxic tumors. Unfortunately, most of the clinical trials aimed to improve tumor oxygenation have not demonstrated clear improvement in patient outcomes, which is mainly attributed to variations in tumor response to hyperoxygenation and the technical inability to measure the oxygen levels in individual patients. The overall objective of Project 2 is to establish EPR oximetry as a routine clinical tool to help clinicians make patient-individualized and informed treatment decisions based on the status of pre-, during, and post-treatment tumor oxygenation. We propose to use an innovative oxygen sensor, called OxyChip, which consists of oxygen-sensing microcrystals encapsulated in a biocompatible polymer matrix. The potential clinical value of OxyChip is that it achieves significantly better signal-to-noise ratio of the EPR signal and more specific localization in the tissue, thereby enabling more sites to be sampled simultaneously, than alternate methods. The sensors will be used in tumors and normal tissues that are sufficiently superficial (within 10 mm of the surface) to be interrogated by a surface-loop coil. We have designed the studies to establish the safety and efficacy of the new technology to obtain data on pO2 data in cancer patients undergoing radiation or chemo treatments. We propose the following specific aims to meet the objective of this project and the overall goals of the PPG: (1) Establish the safety and efficacy of OxyChip for repeated measurement of pO2 in untreated cancer patients and in patients receiving radiation therapy. (2) Characterize spatial and temporal changes in pO2 in human tumors for time periods of minutes, days, and weeks using OxyChip. (3) Determine pO2 response to hyperoxygenation interventions in human tumors. (4) Monitor pO2 dynamics in human tumors and surrounding tissues following radiation/surgical therapy. (5) Determine pO2 levels and effect of hyperoxygenation on the efficacy of neoadjuvant Trastuzumab therapy to HER2+ breast cancer patients. The studies will be performed using a selected set of human tumors where a knowledge of hypoxia and interventional oxygen treatment are expected to be highly important. The proposed work addresses a clinically relevant and timely need to establish the use of EPR oximetry for reliable and repeated pO2 measurement in tumors.

抽象的 缺氧是许多人类肿瘤的常见特征。缺氧会导致恶性潜能增加，包括 转移和复发率较高。最重要的是，缺氧会损害肿瘤对辐射的反应， 某些化疗。因此，人们在提高氧气含量方面投入了大量的精力。 缺氧肿瘤。不幸的是，大多数旨在改善肿瘤氧合的临床试验并没有 患者预后明显改善，这主要归因于肿瘤的变化 对过度氧合的反应以及技术上无法测量个体患者的氧气水平。 项目 2 的总体目标是将 EPR 血氧测定法建立为常规临床工具，以帮助临床医生 根据治疗前、治疗期间和治疗后的状态做出患者个性化和知情的治疗决策 肿瘤氧合。我们建议使用一种创新的氧气传感器，称为 OxyChip，它由 氧传感微晶封装在生物相容性聚合物基质中。潜在的临床价值 OxyChip 的优点是它实现了 EPR 信号显着更好的信噪比和更特异的 定位在组织中，从而比其他方法能够同时对更多部位进行采样。 这些传感器将用于肿瘤和足够浅层的正常组织（距离肿瘤 10 毫米以内） 表面）由表面环路线圈询问。我们设计了这些研究来确定安全性和 新技术在接受放射或化疗的癌症患者中获取 pO2 数据的功效 治疗。为了实现该项目的目标和总体目标，我们提出以下具体目标 PPG：(1) 确定 OxyChip 用于重复测量未经治疗的 pO2 的安全性和有效性 癌症患者和接受放射治疗的患者。 (2) 表征空间和时间变化 使用 OxyChip 在几分钟、几天和几周的时间段内检测人类肿瘤的 pO2。 (3) 测定 pO2 对人类肿瘤过度氧合干预的反应。 (4) 监测人类肿瘤中的 pO2 动态 放射/手术治疗后的周围组织。 (5) 确定 pO2 水平和效果 高氧合对 HER2+ 乳腺癌患者新辅助曲妥珠单抗治疗疗效的影响。这 将使用一组选定的人类肿瘤进行研究，其中了解缺氧和 介入氧疗预计非常重要。拟议的工作涉及临床 相关和及时的需要建立 EPR 血氧测定法的使用，以进行可靠和重复的 pO2 测量 肿瘤。