T1 OXYMETRY ON HIGH GRADE BRAIN TUMOR WITH ANTIANGIOGENIC THERAPY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 GBM大量表达整合素v 3。我们已经开发出一种靶向纳米颗粒，可以与这种整合素结合，并将治疗剂直接输送到这些肿瘤血管。通过将自杀基因(突变的Raf基因(NP-ATP？-Raf))与这种纳米颗粒复合，我们成功地治疗了原位大鼠脑瘤模型。该基因破坏了血管内皮细胞生长因子和成纤维细胞生长因子介导的导致内皮细胞凋亡的信号通路。在大鼠RT2和C6肿瘤模型上观察到显著的肿瘤消退和长期存活。由于这种方法破坏了肿瘤血管，我们预计治疗后肿瘤的氧合会下降，并希望使用体内MRI技术跟踪治疗后发生的变化的时间进程。 分子氧(O2)是顺磁性的。它在组织中的存在改变了氢核磁共振的纵向弛豫速率r1。R1与O2分压(PO2)呈线性关系。因此，我们可以通过测量增量r1来确定增量pO2。最近，一种快速的T1映射方法被开发出来，该方法可以在几秒钟内获得多层T1映射，使得沿时间进程的动态映射成为可能。结果表明，该方法可以量化运动视觉任务中静息状态和功能激活状态之间的脑氧合变化。 这项研究的目的是进行T1血氧测量，以调查与未治疗的对照组相比，我们的抗血管生成纳米颗粒治疗后氧合水平是如何改变的。 方法 将大鼠胶质瘤细胞系RT2细胞接种于雄性Fisher大鼠脑内。他们被分成两组。治疗组(第1组)接受治疗纳米粒。对照组(2组)注射生理盐水。另一对照组(第3组)为正常动物，未经肿瘤或治疗。行T2加权MR扫描，获得肿瘤大小。然后用T1标测血氧测定法评估肿瘤进展不同阶段的氧合情况。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. GBM expresses the integrin ¿v¿3 in abundance. We have developed a targeted nanoparticle that can bind to this integrin and deliver therapeutic agents directly to these tumor vessles. By complexing a suicide gene (mutated Raf gene (NP-ATP¿-Raf)) to this nanoparticle, we have successfully treated orthotopic rat brain tumor models. This gene disrupts the VEGF and FGF mediated signaling pathways that result in endothelial cell apoptosis. Significant tumor regression and long term survival have been observed on the rat RT2 and C6 tumor models. Because this approach destroys tumor vessels, we expect a drop in the oxygenation of the tumor in response to treatment and would like to follow the time course of changes that occur after treatment using in vivo MRI techniques. Molecular oxygen (O2) is paramagnetic. Its presence in the tissue changes the longitudinal relaxation rate R1 of hydrogen NMR. R1 exhibits a linear relationship with the partial pressure of O2 (pO2). Thus we can determine Delta pO2 by measuring Delta R1. Recently, a fast T1 mapping method was developed which can obtain a multi-slice T1 map in just a few seconds, making dynamic mapping along a time course feasible. It is shown that this method can quantify the oxygenation change in the brain between the resting and functionally activated states in a motor-visual task. The purpose of this study was to perform T1 oxymetry measurement to investigate how the oxygenation level is altered with the treatment of our anti-angiogenic nanoparticle as compared to untreated contols. Methods RT2 (Rat glioma cell line) cells were implanted intracranially in male Fisher Rats. They were divided to two groups. Treated groups (Group 1) received the therapeutic nanoparticles. Control groups (Group 2) received saline. Another control group (Group 3) consist of normal animals without tumor or treatment. T2-weighted MR is performed to obtain the tumor size. T1 mapping oxymetry is then performed to evaluate the oxygenation at different stages of tumor progression.