In Vivo Cell Tracking with PET

 描述（由申请人提供）：仍然迫切需要用于递送到梗塞心肌的干细胞的体内细胞追踪的改进方法，作为再生治疗的手段。在本申请中，我们提出开发和比较两种不同的基于PET的细胞跟踪方法。第一种方法使用具有3.3 d半衰期的正电子发射体89 Zr直接标记心脏造血间充质干细胞（CMSC），该半衰期与PET在2-3周内体内监测标记细胞分布的结果非常匹配。我们已经开发了一种用于标记基于细胞的产物的新的2步程序，其包括制备新的89 Zr标记中间体，所述中间体共价结合至细胞表面蛋白的残基，标记后的细胞流出可忽略不计。第二种方法需要用人钠/碘同向转运体（hNIS）基因转染CMSC，并通过PET成像结合碘类似物PET探针18F-四氟硼酸盐体内跟踪细胞。在这个建议中，我们将调查的灵敏度和定量准确性的特点，这两个PET为基础的非侵入性细胞跟踪方法在一个良好的特点，小鼠心肌梗死模型。

 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.