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

摘要 缺氧是许多人类肿瘤的共同特征。缺氧导致恶性潜能增加，包括 转移率高，复发率高。最重要的是，缺氧损害了肿瘤对辐射和 一定要接受化疗。因此，相当大的努力一直集中在提高空气中的氧含量。 缺氧性肿瘤。不幸的是，大多数旨在改善肿瘤氧合的临床试验都没有。 患者预后有明显改善，这主要归因于肿瘤的差异 对高氧的反应和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血氧仪建立为常规的临床工具，以帮助临床医生 基于治疗前、治疗中和治疗后状态的患者个性化和知情的治疗决定 肿瘤氧合作用。我们建议使用一种创新的氧气传感器，称为氧气芯片，它包括 氧敏微晶包裹在生物相容的聚合物基质中。其潜在的临床应用价值 OxyChip是它实现了明显更好的EPR信号的信噪比，并且更具体 在组织中定位，从而比替代方法能够同时采样更多的部位。 传感器将用于肿瘤和正常组织，这些组织足够浅(在10毫米以内 表面)由表面回路线圈询问。我们设计了这些研究，以确定安全和 这项新技术获取癌症放疗或化疗患者氧分压数据的有效性 治疗。我们提出了以下具体目标，以实现本项目的目标和 PPG：(1)建立OxyChip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)描述空间和时间变化 使用OxyChip在人类肿瘤中持续几分钟、几天和几周的时间段的PO2。(3)测定氧分压 人类肿瘤对高氧干预的反应。(4)监测人体肿瘤的氧分压动态，并 放射/手术治疗后的周围组织。(5)测定PO2水平及其影响 高氧对HER2乳腺癌患者新辅助曲妥珠单抗治疗效果的影响。这个 研究将使用一组选定的人类肿瘤进行，在这些肿瘤中，对缺氧和 介入性氧疗被认为是非常重要的。这项拟议的工作涉及一种临床上的 相关的和及时的需要建立使用EPR血氧测定仪来可靠和重复地测量 肿瘤。

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.