T1 OXYMETRY ON HIGH GRADE BRAIN TUMOR WITH ANTIANGIOGENIC THERAPY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。我们已经开发了一种具有<$v <$3配体的阳离子抗血管生成纳米颗粒（NP），其靶向表达整合素<$v <$3的肿瘤内皮细胞。GBM已显示在其血管上含有该整合素的高表达。这种治疗性NP携带突变的Raf基因（NP-ATP <$-Raf）复合物。该基因破坏导致细胞凋亡的VEGF和FGF介导的信号传导途径。在使用这种治疗性纳米颗粒治疗的大鼠RT 2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NMR的纵向弛豫速率R1。 R1与O2分压（pO 2）呈线性关系。 因此，我们可以通过测量Δ R1来确定Δ pO 2。 最近，开发了一种快速T1标测方法，该方法可以在短短几秒钟内获得多切片T1标测图，使得沿沿着时间进程的动态标测成为可能。 结果表明，该方法可以量化的运动视觉任务中的休息和功能激活状态之间的大脑中的氧合变化。 本研究的目的是进行T1血氧测量，以研究如何随着我们的抗血管生成纳米颗粒的治疗沿着肿瘤进展改变氧合水平。 方法 将颅内植入RT 2（大鼠神经胶质瘤细胞系）细胞的8-10周龄雄性Fisher大鼠分成两组。 治疗组（第1组）将接受治疗性纳米颗粒。对照组（第2组）将接受生理盐水。 还将使用另一个对照组（第3组），其中包括无肿瘤和治疗的正常动物。将进行T2加权MR以获得肿瘤大小。将进行T1标测血氧测定，以评价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.