MRI IMAGING OF TUMOR HYPOXIA

放射诊断领域正在经历一场悄无声息的革命。虽然过去放射学的重点是 解剖学，在过去的十年里出现了非侵入性询问组织/肿瘤的技术 功能和分子表型。这个新项目的目标是整合和改进 功能和分子成像在氧化还原活性抗癌药物开发中的应用。之前 我们小组和其他人的工作已经确定了许多用于药物治疗的有用的磁共振成像终点， 包括扩散磁共振、动态增强(DCE)磁共振和1H/31P磁共振 波谱(MRS)。因为这些都是开发的，只需要应用程序，所以这些端点是 包含在生物标志物核心C中。这个项目的目的是开发更新的氧化还原敏感的对比。 在此程序中使用的机制。具体地说，我们将研究(目标1)R2*成像(也称为 血氧水平依赖，或BOLD成像)，(目标2)具有高分子对比度的DCE成像 以及(目标3)可与血清硫醇可逆相互作用的新型造影剂。所有AIMS将专注于 开发成像方法，在治疗前经验性地确定哪些患者最有可能受益 来自氧化还原活性抗癌药物(“Theragnostics”)。这样的能力可能会对 临床试验设计和患者管理。一个重要的次要目标将是使用成像 用于监测治疗开始后反应的生物标志物。这些方法将主要是 在临床前无名模型中进行，并尽快转化为临床试验。

The field of diagnostic radiology is undergoing a quiet revolution. While radiology in the past has focused on anatomy, techniques have emerged over the past decade to non-invasively interrogate tissue/tumor functions and molecular phenotypes. The goal of this new project is to incorporate and improve the application of functional and molecular imaging to the development of redox active anti-cancer drugs. Prior work by our group and others has identified a number of useful MR imaging endpoints for drug therapy, including diffusion MRI, dynamic contrast enhanced (DCE) MRI, and 1H/31P magnetic resonance spectroscopy (MRS). Because these are developed and only need application, these endpoints are contained in the biomarkers core C. The aims of this project are to develop newer redox-sensitive contrast mechanism for use in this program. Specifically, we will investigate (Aim 1) R2* imaging (also known as blood oxygen level dependent, or BOLD, imaging), (Aim 2) DCE imaging with high molecular weight contrast agents, and (Aim 3) novel contrast agents that will reversibly interact with serum thiols. All aims will focus on developing imaging approaches to empirically identify, prior to therapy, those patients most likely to benefit from redox active anti-cancer drugs ("theragnostics"). Such a capability could have an important impact on clinical trial design and patient management. An important secondary goal will be the use of imaging biomarkers to monitor response after commencement of therapy. These approaches will primarily be conducted in pre-clinical anaimal models, and translated to the clinical trials as soon as appropriate.