In Vivo Cell Tracking with PET

使用 PET 进行体内细胞追踪

• 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
• 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

 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.