RAT BRAIN TUMOR METABOLISM AND PROGRESS W/ANTIANGIOGENIC NANOPARTICLE THERAPY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。前言：胶质母细胞瘤是一种预后差、生存率低的原发脑肿瘤。本研究的目的是监测在使用或不使用抗血管生成治疗的大鼠脑胶质瘤模型中肿瘤进展过程中的代谢变化。这种新的基于纳米颗粒(NP)的抗血管生成方法是一种非病毒基因递送系统，使用？V？3靶向肿瘤血管。突变的RAF基因被传递到肿瘤内皮细胞中，以引起细胞凋亡。使用放射性示踪剂18F-FDG的PET成像监测葡萄糖代谢；使用T2加权MRI表征肿瘤进展。方法和讨论：用18F-FDGPET监测葡萄糖摄取，并用T2加权MR序列记录肿瘤大小：治疗组(n=5)和对照组(n=5)大鼠原位移植大鼠胶质瘤RT2细胞。正常大鼠(n=3)无肿瘤或治疗。对照组大鼠注射生理盐水。治疗组大鼠在肿瘤植入后第6天至第10天期间接受3次靶向携带突变的Raf基因复合体的NP治疗。对照组和正常组动物在相同日期进行正电子发射计算机断层扫描和磁共振成像。PET和MRI图像均显示，在治疗早期，治疗动物的脑内FDG摄取增加，T2信号增强，随后从肿瘤植入后第10天开始，肿瘤区域的信号持续减少。这种模式一直持续到研究结束。对照组动物在肿瘤区域有较高的FDG摄取率和T2信号，直到肿瘤植入后15~27天死亡。没有肿瘤的动物的PET/MRI图像正常。

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. Introduction: Glioblastoma is a primary brain tumor with poor prognosis and low survival rate. The purpose of this study is to monitor metabolic changes during tumor progression with or without anti-angiogenic treatment in a rat glioma model. This novel nanoparticle (NP)-based anti-angiogenic approach is a non-viral gene delivery system using ?v?3 to target tumor vasculature. A mutated raf gene is delivered to cause apoptosis in tumor endothelium. Glucose metabolism is monitored using PET imaging with radio-tracer 18F-FDG; and tumor progression is characterized using T2-weighted MRI. Methods and Discussion: Animals in the following three groups were imaged between days 6 ¿ 24 with 18F-FDG PET to monitor glucose uptake, and with T2-weighted MR sequences to record tumor size: Treated rats (n=5) and control rats (n=5) with orthototopic rat gliomas RT2 cells. Normal rats (n=3) had no tumor or treatment. Control rats received saline. Treated rats received an ?v?3 targeted NP carrying a mutated Raf gene complex three times between days 6 ¿ 10 after tumor implantation. Animals in the control and normal groups were imaged on PET and MR on the same dates. Both PET and MRI images showed that the treated animals had an increased FDG uptake and elevated T2 intensity in the brain early in the treatment period, followed by a constant decrease of signal in the tumor area starting day 10 after tumor implantation. This pattern lasted until the termination of the study. Control animals had a high FDG uptake and T2 intensity in tumor area until they deceased between 15 to 27 days post tumor implantation. Animals with no tumor had normal PET/MRI images.