Imaging Metabolism with Hyperpolarized 13C-Labeled Cell Substrates
Journal of the American Chemical Society
American Chemical Society
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Brindle, K. (2016). Imaging Metabolism with Hyperpolarized 13C-Labeled Cell Substrates. Journal of the American Chemical Society, 137 6418-6427. https://doi.org/10.1021/jacs.5b03300
Non-invasive 13C magnetic resonance spectroscopy measurements of the uptake and subsequent metabolism of 13C-labeled substrates is a powerful method for studying metabolic fluxes in vivo. However the technique has been hampered by a lack of sensitivity, which has limited both the spatial and temporal resolution. The introduction of dissolution dynamic nuclear polarization in 2003, which by radically enhancing the nuclear spin polarization of 13C nuclei in solution can increase their sensitivity to detection by more than 104-fold, has revolutionized the study of metabolism using magnetic resonance, with temporal and spatial resolutions in the seconds and millimeter ranges respectively. The principle limitation of the technique is the short half-life of the polarization, which at ~20 – 30 s in vivo, limits studies to relatively fast metabolic reactions. Nevertheless, pre-clinical studies with a variety of different substrates have demonstrated the potential of the method to provide new insights into tissue metabolism and have paved the way for the first clinical trial of the technique in prostate cancer. The technique now stands on the threshold of more general clinical translation. I consider here what the clinical applications might be, which are the substrates that most likely will be used, how will we analyze the resulting kinetic data and how we might further increase the levels of polarization and extend polarization lifetime.
The work in KMB’s laboratory on imaging metabolism with hyperpolarized 13C-labeled cell substrates is currently sup-ported by grants from Cancer Research UK (17242, 16465), a Wellcome Trust Strategic Award (095962) and a Marie Curie Initial Training Network (EUROPOL).
Wellcome Trust (095962/Z/11/Z)
External DOI: https://doi.org/10.1021/jacs.5b03300
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253440