RAT BRAIN TUMOR METABOLISM AND PROGRESS W/ANTIANGIOGENIC NANOPARTICLE THERAPY

点击翻译按钮获取中文摘要

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.