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。缺氧会导致恶性潜力提高 转移和更高的复发率。最重要的是，缺氧会损害肿瘤对辐射的反应和 某些化学疗法。因此，大量努力集中在改善的氧气含量上 低氧肿瘤。不幸的是，旨在改善肿瘤氧合的大多数临床试验尚未 表现出明显改善的患者结局，这主要归因于肿瘤的变化 对高氧化的反应以及无法测量个别患者的氧气水平的技术。 项目2的总体目标是建立EPR血氧仪作为常规临床工具，以帮助临床医生使 根据治疗前，期间和治疗的状态 肿瘤氧合。我们建议使用一种创新的氧气传感器，称为Oxychip，该传感器由 氧化微晶包裹在生物相容性聚合物基质中。潜在的临床价值 OxyChip是，它的EPR信号的信噪比明显更好，并且更具体 与替代方法相比，在组织中定位，从而使更多的位点被同时进行采样。 传感器将用于足够表层的肿瘤和正常组织（在10 mm的范围内 表面）要被表面环线圈审问。我们设计了研究以建立安全性和 新技术获得有关辐射或化学疗法的癌症患者的PO2数据数据的功效 治疗。我们提出以下具体旨在满足该项目的目标的目的以及 PPG：（1）建立Oxychip在未处理中重复测量PO2的安全性和功效 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的时间，几分钟和几周的人类肿瘤中的PO2。 （3）确定PO2 对人肿瘤中高氧干预措施的反应。 （4）监测人类肿瘤中的PO2动力学 辐射/手术治疗后的周围组织。 （5）确定PO2级别和效果 新辅助曲妥珠单抗治疗对HER2+乳腺癌患者的疗效的高氧化。这 将使用一组选定的人类肿瘤进行研究，其中缺氧和 介入的氧气处理预计将非常重要。拟议的工作在临床上解决 相关且及时的需要建立EPR血氧仪用于可靠和重复的PO2测量 肿瘤。