Assessment of BBB Disruption during RT using DCE MRI

描述（由申请人提供）：虽然放射治疗对高级别胶质瘤脑转移患者的中位生存期增加有一定影响，但这些患者通常仍局部进展，表明需要改善手段控制。化疗与放疗联合使用并未显示出显著的改善，化疗的有限附加益处可能部分是由于抑制穿过血脑屏障（BBB）的大分子尺寸。然而，辐射毒性研究的结果表明，辐射可能会使内皮紧密连接松动，从而增加大分子向辐照组织的转运。由于肿瘤区域的剂量明显高于递送至大多数正常脑的剂量，因此这种效应事实上增加了所施用药剂的摄取的特异性。这可以提供一个机会窗口，以提高化疗剂或放射增敏剂在放射治疗期间向肿瘤细胞递送的效率。需要更好地了解这种辐射效应，以确定潜在的优势，因为到目前为止，时间剂量和体积依赖性以及修复的时间过程还没有得到很好的理解。本研究响应NCI/NIH/DHHS（PA-04-045）的体内癌症成像探索/开发赠款申请，建议系统地表征正常脑和肿瘤血管通透性对MRI造影剂的依赖性，MRI造影剂的分子大小与许多化疗剂相似。患者接受高级别胶质瘤或脑转移瘤的放疗后，将进行一系列动态增强（DCE）MRI扫描。将分析来自这些扫描的数据以量化血管渗透性，其与肿瘤与正常脑组织中的剂量、体积、时间和存在相关。

DESCRIPTION (provided by applicant): While radiotherapy has made some impact on increased median survival for patients with high-grade glic brain metastases, these patients still generally progress locally, indicating the need for improved means control. The use of chemotherapy in combination with radiation has not shown significant improvement it is possible that the limited added benefit of chemotherapy is in part due to the large molecular size of inhibiting transport across the blood-brain barrier (BBB). Findings from radiation toxicity studies, however, reveal that radiation may loosen endothelial tight junctions, thus increasing transport of large molecules to irradiate tissue. As the dose to the tumor region is markedly higher than that delivered to most normal brain, this effect fact increase specificity of uptake of administered agents. This may provide a window of opportunity to improve efficiency of delivery of chemotherapeutic agents or radiosensitizers to tumor cells during radiotherapy. The of this radiation effect needs to be better understood to determine potential advantage, as to date, the time dose and volume dependence, and time course of repair are not well understood. This study, in response to a for applications on In Vivo Cancer Imaging Exploratory/Developmental grants from NCI/NIH/DHHS (PA-04-045 proposes to systematically characterize these dependencies on vascular permeability of normal brain and tumor to a MRI contrast agent that has a molecule size similar to many chemotherapeutic agents. Patient's und radiotherapy for high-grade gliomas or brain metastases will be followed by a sequence of dynamic c enhanced (DCE) MRI scans. Data from these scans will be analyzed to quantify vascular permeability, which related to dose, volume, time, and presence in tumor versus normal brain tissue.