Direct and Repeated Clinical Measurement of pO2 for Enhancing Cancer Therapy

描述（由申请人提供）：尽管全身治疗取得了进展，但氧气仍然是所有放射增敏剂中最有效的，使灵敏度增加了3倍。氧分压因个体、一天中的时间和所研究的器官而异。众所周知，许多自然（如肿瘤生长）和治疗过程会动态改变肿瘤中的pO 2，并且肿瘤中的pO 2在同一阶段具有相同类型肿瘤的个体之间存在差异。通过聪明地、适应性地利用对肿瘤内氧张力的更好理解，潜在的收益是巨大的。目前还没有临床方法来获得治疗条件下肿瘤pO 2的准确定量测量。本PPG提案的目的是改变这种情况，引入一种实用有效的技术，为临床医生测量肿瘤和其他组织中的pO 2提供一种直接、可重复、定量的方法。该方法基于EPR血氧测定法，该方法已在一小组癌症患者中进行了广泛的临床前评估和可行性测试。这种方法将能够个性化治疗和验证旨在通过放射生物学显著量增加肿瘤中pO 2的方法。PPG是三个机构的合作成果：达特茅斯是开发临床适用的EPR血氧测定技术的研究中心，并拥有开发体内EPR仪器和技术的广泛基础设施;布鲁塞尔与达特茅斯一起成为许多证明EPR血氧测定有效性的关键临床前研究的重要来源;埃默里大学拥有领先的放射肿瘤学学术项目，并与达特茅斯合作使用体内EPR系统。PPG分为三个项目，每个项目涉及所有3个机构，并利用不同但互补的方法来推进临床EPR血氧测定。PPG的目的是证明已经实现了具有可用于直接和重复测量肿瘤pO 2的临床适用方法的能力，并且确实提供了使临床医生能够利用可通过pO 2重复测量获得的增强治疗机会所需的测量类型。它还将确定通过EPR定量测量肿瘤pO 2与间接但目前更广泛使用的用于推断肿瘤缺氧的临床方法之间的关系。该PPG的成功将使未来的临床试验成为可能，其中来自这些测量的信息被应用于改变治疗并确定对结果的影响。

DESCRIPTION (provided by applicant): Despite advances in systemic therapy, oxygen remains the most potent of all radiation sensitizers, increasing sensitivity by a factor of 3. Oxygen tension varies by individual, by time of day, and by organ being studied. It also is well known that many of the natural (e.g. tumor growth) and therapeutic processes change the pO2 in tumors dynamically and that pO2 in tumors varies among individuals with the same type of tumor in the same stage. The potential gains by making smart, adaptive use of an improved understanding of the oxygen tension within a tumor are enormous. Currently there are no clinical methods to obtain accurate, quantitative measurements of tumor pO2 under treatment conditions. The purpose of this proposal for a PPG is to change this situation, introducing a practical and effective technology to provide a direct, repeatable, quantitative method for clinicians to measure pO2 in tumors and in other tissues. This method is based on EPR oximetry, which has undergone extensive preclinical evaluation as well as feasibility testing in a small set of cancer patients. This method will be able to individualize therapy and validate methods aimed at increasing the pO2 in tumors by radiobiologically significant amounts. The PPG is a collaborative effort of three institutions: Dartmouth which has been the site that has developed clinically applicable EPR oximetry techniques and which has an extensive infrastructure for the development of in vivo EPR instruments and techniques; Brussels which has together with Dartmouth been a very significant source of many of the key preclinical studies demonstrating the effectiveness of EPR oximetry; and Emory University which has a leading academic Radiation Oncology program and has previous and ongoing collaboration with Dartmouth using in vivo EPR system. The PPG is organized in three projects, with each project involving all 3 institutions and utilizing different but complimentary approaches to advance clinical EPR oximetry. The goals of the PPG are to demonstrate that the capability of having a clinically applicable method available for direct and repeated measurements of tumor pO2 has been realized and does indeed provide the types of measurements required to enable clinicians to exploit the enhanced therapeutic opportunities that can be obtained by repeated measurements of pO2. It also will determine the relationships between the quantitative measurements of tumor pO2 by EPR with the indirect but currently more widely available clinical methods used to infer to tumor hypoxia. The success of this PPG will make future clinical trials possible where the information from these measurements is applied to change treatment and the effects on outcomes determined.