Advances in fluorine-19 cellular MRI to study inflammation and cancer.

摘要

Longitudinal non-invasive visualization of cellular events in intact organisms would substantially increase our understanding of the spatial and temporal dynamics of biological processes. In vivo cell tracking using fluorine-19 MRI and perfluorocarbon is a promising new technology for quantitative cellular and molecular MRI. In order to advance 19F MRI technology for cell tracking applications, we formulated stable perfluorocarbon nanoemulsions and characterized cell labeling efficiency and cytotoxicity for variety of cell types. We applied 19F cell tracking technology for studying inflammation and cancer: (1) We characterized and quantified inflammation in a mouse model of inflammatory bowel disease (IBD) and studied response to treatment by labeling macrophages in situ, (2) we studied antigen specific T cells trafficking in a related mouse model of IBD and discovered a possible link between IBD and pancreatitis, (3) we developed a novel method to measure intracellular pO2 and applied this technique to a rat glioma model and studied changes in intracellular pO2 in response to treatment, and (4) we developed a novel 19F agent, perfluorotertbutyl ether (PFTE), for multi-spectral MRI that can be used to study cell-cell interactions in vivo. We validated our results extensively by histology, immunohistochemistry and qRT PCR. Our results demonstrate that 19F MRI is a versatile technology with a broad spectrum of applications in biomedicine.