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.
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 cell tracking approaches that utilize positron emission tomography (PET). 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 o 2- 3 weeks. 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.
| Hickey, Raymond D; Mao, Shennen A; Glorioso, Jaime et al. (2016) Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1. Sci Transl Med 8:349ra99 |
| Jiang, Huailei; Bansal, Aditya; Pandey, Mukesh K et al. (2016) Synthesis of 18F-Tetrafluoroborate via Radiofluorination of Boron Trifluoride and Evaluation in a Murine C6-Glioma Tumor Model. J Nucl Med 57:1454-9 |
