RAT BRAIN TUMOR METABOLISM AND PROGRESS W/ANTIANGIOGENIC NANOPARTICLE THERAPY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心机构，不一定为研究者机构。胶质母细胞瘤是一种预后差、生存率低的原发性脑肿瘤。本研究的目的是在大鼠胶质瘤模型中监测肿瘤进展期间的代谢变化，有或没有抗血管生成治疗。这种新的纳米粒子（NP）为基础的抗血管生成的方法是一种非病毒基因传递系统使用？v？3靶向肿瘤血管。突变的raf基因被递送以引起肿瘤内皮细胞凋亡。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：在第6至24天之间，对以下三组动物进行18F-FDG PET成像以监测葡萄糖摄取，并使用T2加权MR序列记录肿瘤大小：治疗组大鼠（n=5）和对照组大鼠（n=5）具有原位大鼠胶质瘤RT 2细胞。正常大鼠（n=3）没有肿瘤或治疗。对照组大鼠接受生理盐水。治疗大鼠接受了一个？v？在肿瘤植入后第6至10天之间，3次靶向携带突变的Raf基因复合物的NP。对照组和正常组的动物在同一天进行PET和MR成像。PET和MRI图像均显示，在治疗期早期，经治疗的动物具有增加的FDG摄取和脑中升高的T2强度，随后在肿瘤植入后第10天开始，肿瘤区域中的信号持续降低。这种模式持续到研究结束。对照组动物在肿瘤区域具有高FDG摄取和T2强度，直到它们在肿瘤植入后15至27天之间死亡。没有肿瘤的动物具有正常的PET/MRI图像。

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.