Determination of Clinical Feasibility of EPR Oximetry of Tumors

描述(由申请人提供)：这些研究的总体目标是证明使用体内EPR血氧测定仪从患者的肿瘤中获得临床有用信息的临床可行性。在这些研究中，我们将重点关注将对临床护理产生最直接和最广泛影响的应用，即重复测量肿瘤pO2的能力。体内EPR将是第一个具有这种能力的临床适用技术。我们的基本假设是，重复测量PO2可用于优化肿瘤治疗，特别是放射治疗和/或联合治疗，以便在治疗比率最大化的时候应用治疗。这种能力还将为许多治疗方法的有效性和作用模式提供非常有用的衡量标准。因此，拟议的研究非常符合这项R21的目标，即建立一种可以显著提高治疗效果的技术的临床可行性。其具体目标是：1.建立在符合临床实践和患者舒适度的条件下对受试者进行有效的肿瘤PO2测量所需的方法学。为了证明这一点，并将氧的非侵入性EPR测量与侵入性技术联系起来，这些技术也有可能直接测量人类受试者的肿瘤氧含量，我们将使用适当的肿瘤模型系统在健康志愿者中进行可行性研究。2.验证可在人体肿瘤中进行测量。我们的假设是，测量可以在具有可接受的数据采集时间的患者(皮肤黑色素瘤皮损患者)中进行，并且可以在不到15分钟(包括设置时间)内获得稳健的P02测量结果，并且在临床实践可接受的约束条件下进行。3.在放射治疗过程中对人体肿瘤的PO2进行系列测量，并开始确定肿瘤在治疗过程中的PO2是否会发生足够的变化，从而具有放射生物学意义。这些测量将在接受放射治疗的患者中进行，这些患者的病变适合在这些初始研究中采用的方法学。我们的假设是，人类肿瘤对电离辐射的氧气反应类似于之前在动物模型中证明的反应。这些研究的次级目标包括：a.将可行性的确定扩大到更广泛的部位和类型的肿瘤；b.确定在临床分次放射治疗的整个过程中跟踪PO2变化的可行性；c.确定连续测量长达120分钟的可行性。

DESCRIPTION (provided by applicant): The overall objective of these studies is to demonstrate the clinical feasibility of using in vivo EPR oximetry to obtain clinically useful information from tumors in patients. In these studies we will focus on the application that will have the most immediate and widespread impact on clinical care, the ability to make repeated non-invasive measurements of tumor pO2. In vivo EPR would be the first clinically applicable technique that has this ability. Our underlying hypothesis is that repeated measurements of pO2 can be used to optimize tumor therapy, especially radiation therapy and/or combined therapy, so that the therapy is applied at times when the therapeutic ratio will be maximized. This capability also will provide very useful measurements of the effectiveness and mode of action of many therapeutic approaches. Thus, the proposed research fits very well with the aim of this R21 to establish the clinical feasibility of a technique that can significantly enhance the efficacy of therapy. The specific aims are: 1. To establish the methodology needed to make valid measurements of tumor pO2 in human subjects under conditions that are compatible with the constraints of clinical practice and comfort of patients. To demonstrate this and to relate the noninvasive EPR measurements of oxygen to invasive techniques that also have the potential for making direct measurements of tumor oxygen in human subjects, we will carry out feasibility studies in healthy volunteers using an appropriate tumor model system. 2. To verify that the measurements can be accomplished in tumors in human subjects. Our hypothesis is that the measurements can be made in patients (patients with cutaneous melanoma lesions) with acceptable data acquisition times and such that robust p02 measurements can be obtained in less than 15 minutes, including setup time, and under conditions that are acceptably within the constraints of clinical practice. 3. To make serial measurements of tumor pO2 in human tumors during the course of radiation therapy and to begin to determine whether the pO2 of tumors will vary during the course of therapy sufficiently to be radiobiologically significant. These measurements will take place in patients undergoing radiation therapy who have lesions that are suitable for the methodology to be employed in these initial studies. Our hypothesis is that human tumors will have responses of oxygen to ionizing radiation similar to those previously demonstrated in animal models. The subaims for these studies include: a. Extending the determination of feasibility to a wider range of sites and types of tumors; b. Determining the feasibility of following changes in pO2 over the full time course of clinical fractionated radiation therapy; c. Determining the feasibility of continuous measurements for up to 120 minutes.