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。 多形性胶质母细胞瘤(GBM)是一种恶性脑肿瘤，其发展依赖于血管生成。我们开发了一种带有3配体的阳离子抗血管生成纳米颗粒(NP)，它针对表达整合素3的肿瘤内皮细胞。已证明GBM在其血管上高表达这种整合素。这种治疗性NPs携带突变的Raf基因(NP-ATP？-Raf)复合体。该基因破坏了血管内皮生长因子和成纤维细胞生长因子介导的导致细胞凋亡的信号通路。在使用该治疗性纳米粒治疗的大鼠RT2肿瘤模型上，观察到显著的肿瘤消退和长期存活。 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，以研究在我们的抗血管生成纳米颗粒治疗过程中，氧合水平是如何随着肿瘤的进展而改变的。 方法 取8~10周龄Fisher雄性大鼠脑内移植RT2细胞，随机分为两组。治疗组(第1组)接受治疗性纳米粒治疗。对照组(2组)给予生理盐水。另一对照组(第3组)为正常动物，无肿瘤及治疗。肿瘤大小由T2加权磁共振成像获得。T1标测血氧仪将用于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. Glioblastoma multiforme (GBM) is a malignant brain tumor whose development depends on angiogenesis. We have developed a cationic antiangiogenic nanoparticle (NP) with ¿v¿3 ligand that targets tumor endothelial cells expressing the integrin ¿v¿3. GBMs have been shown to contain high expression of this integrin on their vessels. This therapeutic NPs carries a mutated Raf gene (NP-ATP¿-Raf) complex. This gene disrupts the VEGF and FGF mediated signaling pathway that results in cell apoptosis. Significant tumor regression and long term survival have been observed on rat RT2 tumor model under treatment using this therapeutic nanoparticle. 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 along the tumor progression with the treatment of our antiangiogenic nanoparticle. Methods Male Fisher Rats with RT2 (Rat glioma cell line) cells implanted intracranially at the age of 8-10 weeks are divided to two groups. Treated group (Group 1) will receive the therapeutic nanoparticles. Control group (Group 2) will receive saline. Another control group (Group 3) with normal animals without tumor and treatment will also be used. T2-weighted MR will be performed to obtain the tumor size. T1 mapping oxymetry will be performed to evaluate the oxygenation at different stages of tumor progression.