In Vivo Cell Tracking with PET

使用 PET 进行体内细胞追踪

基本信息

批准号：
9042531
负责人：
Timothy R. DeGrado
金额：
$ 22.38万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9042531
关键词：
Amines Binding Boron Cell Surface Proteins Cells Characteristics Clinical Deferoxamine Detection Development Diagnostic Discipline of Nuclear Medicine Echocardiography Engraftment Evaluation Fluorides Gene Expression Genes Gold Half-Life Hour Human Image Infarction Inferior Injection of therapeutic agent Iodides Label Learning Mesenchymal Stem Cells Methods Modeling Modification Monitor Mus Myocardial Myocardial Infarction Myocardium Natural regeneration Oxyquinoline Phenotype Positron Positron-Emission Tomography Preparation Procedures Radioactivity Reaction Reporter Genes Resolution Reverse Transcriptase Polymerase Chain Reaction SLC5A5 gene Stem cell transplant Stem cells Techniques Time Tissues Transfection analog base cell behavior cell motility cellular imaging comparative functional improvement imaging modality imaging system improved in vivo in vivo imaging innovation interest novel programs public health relevance regenerative therapy response single photon emission computed tomography

项目摘要

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.

描述（由申请人提供）：仍然迫切需要改进用于递送至梗塞心肌的干细胞的体内细胞追踪的方法，作为再生治疗的手段。在本申请中，我们建议开发和比较两种不同的基于PET的细胞追踪。第一种方法使用正电子发射体 89Zr 直接标记心肌间充质干细胞 (CMSC)，其半衰期为 3.3 天，与通过 PET 在 2-3 周的时间内体内监测标记细胞的分布情况我们开发了一种新颖的两步程序，用于标记基于细胞的产品，其中包括制备与细胞残基共价结合的新型 89Zr 标记中间体。第二种方法需要用人钠/碘同向转运体 (hNIS) 基因转染 CMSC，并对细胞进行体内跟踪。通过 PET 成像结合碘化物模拟 PET 探针 18F-四氟硼酸盐在本提案中，我们将研究两种基于 PET 的无创细胞追踪方法在特征明确的小鼠心肌梗死模型中的灵敏度和定量准确性特征。