Assessment of BBB Disruption during RT using DCE MRI

描述(申请人提供)：虽然放射治疗对高级别脑转移瘤患者的中位生存期增加有一些影响，但这些患者总体上仍在局部进展，这表明需要改进手段控制。化疗与放疗的联合应用并未显示出显着改善，化疗的有限额外益处可能部分是由于抑制血脑屏障(BBB)转运的大分子。然而，辐射毒性研究的结果显示，辐射可能会疏松内皮细胞紧密连接，从而增加大分子向照射组织的运输。由于肿瘤区域的剂量明显高于大多数正常脑组织的剂量，这一效应事实上增加了给药药物摄取的特异性。这可能为提高放射治疗期间化疗药物或放射增敏剂对肿瘤细胞的输送效率提供机会之窗。需要更好地了解这种辐射效应的影响，以确定潜在的优势，因为到目前为止，对时间剂量和体积的依赖性以及修复的时间过程还没有很好的了解。这项研究是为了响应NCI/NIH/DHHS(PA-04-045)申请的活体肿瘤成像探索/开发补助金(PA-04-045)，建议系统地表征这些对正常大脑和肿瘤对分子尺寸类似于许多化疗药物的MRI造影剂的血管渗透性的依赖。对高级别胶质瘤或脑转移瘤患者进行放射治疗后，将进行动态增强(DCE)MRI扫描。这些扫描的数据将被分析以量化血管渗透性，这与剂量、体积、时间和肿瘤与正常脑组织的存在有关。

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.