胶质瘤是最常见的原发性脑肿瘤，严重威胁人类健康。以自杀基因为代表的基因治疗技术是近年来研究的热点，但缺乏高效的基因转移载体和有效的活体示踪手段是困扰该技术发展的难题。课题组前期研究证实内皮祖细胞（EPCs）向胶质瘤特异性归巢，与胶质瘤细胞构成马赛克样管腔结构，可作为携带治疗性基因的载体。本项目拟采用EPCs作为携带自杀基因(TK)的载体靶向治疗胶质瘤，并利用铁蛋白报告基因(FTH)磁共振成像技术对其治疗的机制和疗效进行深入研究。一是利用EPCs靶向归巢至胶质瘤的特性，将自杀基因运输到肿瘤组织达到抑制肿瘤生长的目的。二是利用磁共振成像定量检测铁蛋白的信号强度，获取自杀基因表达的部位、幅度及持续时间等信息，同时采用磁共振多模态成像评估肿瘤的大小、血流灌注等形态学及功能学方面的变化，从而定量监控基因治疗的疗效。研究有望为胶质瘤基因治疗提供新的途径，并为基因治疗的无创性活体示踪提供新的技术手段。

Glioma is the most common form of primary brain tumor that seriously threatens human health. There is no cure for glioma so far. In recent years, research on gene therapy using suicide gene has drawn much attention in glioma treatment. However, two important factors, effective gene delivery vehicle and in vivo/no-invasive tracking/monitor of treatment have limited the development of suicide gene therapy. Our previous work demonstrated that endothelial progenitor cells (EPCs) have the ability of specific homing towards glioma, thus EPCs can be used as an effective vehicles for transfer the therapeutic genes. Recombinant Ferritin expression in combination with agnetic resonance imaging has been employed as effective in vivo tracking technique in several types of tumors. In this project, we plan to build a gene expression cassette that enable the non-fusion, co-expression of TK, a suicide gene for killing cancer cells, and ferritin, an effective reporter for in vivo tracking of the treatment. We will use EPCs as gene delivery vehicle to transfer the gene cassette. We plan to complete two major goals: 1) using EPCs as vehicle to deliver the gene therapy cassette that co-expresses both suicide gene TK and tracking reporter gene Ferritin; 2) tracking/monitoring the expression and effect of suicide gene by detecting Ferritin using MRI, specifically using MR R2-maping technology, to acquire clear three-dimensional, anatomical, and functional images. The unique combination of tracking gene expression along with the suicide gene will enable active monitoring on the expression level, location, and duration of suicide gene, thus the efficacy of the gene therapy. We anticipate that the completion of this project will provide a new technological platform for in vivo tracking of gene therapy that we hope, will help to find the cures for glioma and other cancers.