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Abstract
Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis.
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Details
1 National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075)
2 National Heart, Lung, and Blood Institute, National Institutes of Health, Chemistry and Synthesis Center, Rockville, USA (GRID:grid.279885.9) (ISNI:0000 0001 2293 4638)
3 Technical University of Denmark, Department of Electrical Engineering, Lyngby, Denmark (GRID:grid.5170.3) (ISNI:0000 0001 2181 8870)
4 National Cancer Institute, National Institutes of Health, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); National Cancer Institute, National Institutes of Health, Radiation Biology Branch, Center for Cancer Research, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075)