In Vivo Cell Tracking with PET

 描述(由申请人提供)：作为再生治疗的一种手段，仍然迫切需要改进体内干细胞追踪移植到梗塞心肌的方法。在这个应用中，我们建议开发和比较两种不同的基于PET的细胞跟踪方法。第一种使用正电子发射体89Zr直接标记心脏间充质干细胞(CMSCs)，半衰期为3.3d，与PET在体内监测标记细胞2-3周的处置相匹配。我们开发了一种新的两步法来标记基于细胞的产品，其中包括制备一种新的89Zr标记中间体，该中间体与细胞表面蛋白的残基共价结合，标记后细胞外流可以忽略不计。第二种方法需要将人钠/碘同向转运体(HNIS)基因导入CMSCs，并通过PET成像结合碘化物类似的PET探针18F-四氟硼酸盐对细胞进行活体跟踪。在这项建议中，我们将在一个特征良好的小鼠心肌梗死模型中研究这两种基于PET的无创细胞跟踪方法的敏感性和定量准确性特征。

 DESCRIPTION (provided by applicant): There remains a critical need for improved methods for in vivo cell tracking of stem cells delivered to infarcted myocardium as a means of regenerative therapy. In this application we propose to develop and compare two different PET-based cell tracking approaches. The first uses direct labeling of cardiopoietic mesenchymal stem cells (CMSCs) with positron-emitter 89Zr that has a 3.3 d half-life that is well-matched for in vivo monitoring of labeled cell dispositions by PET over periods of 2-3 weeks. We have developed a novel 2-step procedure for labeling cell-based products that includes preparation of a novel 89Zr-labeling intermediate that covalently binds to residues of cell-surface proteins with negligible cellular efflux post- labeling. The second approach entails transfection of the CMSCs with the human sodium/iodide symporter (hNIS) gene, and in vivo tracking of the cells by PET imaging in conjunction with the iodide analog PET probe, 18F-tetrafluoroborate. In this proposal, we will investigate the sensitivity and quantitative accuracy characteristics of both PET-based noninvasive cell tracking approaches in a well-characterized murine myocardial infarction model.