Probing hepatic metabolism of [2-<sup>13</sup>C]dihydroxyacetone in vivo with <sup>1</sup>H-decoupled hyperpolarized <sup>13</sup>C-MR.
Timm, Kerstin N
Magma (New York, N.Y.)
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Marco-Rius, I., Wright, A., Hu, D., Savic, D., Miller, J. J., Timm, K. N., Tyler, D., et al. (2021). Probing hepatic metabolism of [2-<sup>13</sup>C]dihydroxyacetone in vivo with <sup>1</sup>H-decoupled hyperpolarized <sup>13</sup>C-MR.. Magma (New York, N.Y.), 34 (1), 49-56. https://doi.org/10.1007/s10334-020-00884-y
ABSTRACT Object: To enhance detection of the products of hyperpolarized [2-13C]dihydroxyacetone metabolism for assessment of three metabolic pathways in the liver in vivo. Hyperpolarized [2 13C] DHAc emerged as a promising substrate to follow gluconeogenesis, glycolysis and the glycerol pathways. However, the use of [2-13C]DHAc in vivo has not taken off because (i) the chemical shift range of [2-13C]DHAc and its metabolic products span over 144 ppm and (ii) 1H decoupling is required to increase spectral resolution and sensitivity. While these issues are trivial for high-field vertical-bore NMR spectrometers, horizontal-bore small-animal MR scanner are seldom equipped for such experiments. Methods: Real-time hepatic metabolism of three fed mice was probed by 1H-decoupled 13C-MR following injection of hyperpolarized [2-13C]DHAc. The spectra of [2-13C]DHAc and its metabolic products were acquired in a 7 T small-animal MR scanner using three purpose-designed spectral-spatial radiofrequency pulses that excited a spatial bandwidth of 8 mm with varying spectral bandwidths and central frequencies (chemical shifts). Results: The metabolic products detected in vivo include glycerol 3-phosphate, glycerol, phosphoenolpyruvate, lactate, alanine, glyceraldehyde 3-phosphate and glucose 6-phosphate. The metabolite-to-substrate ratios were comparable to those reported previously in perfused liver. Discussion: Three metabolic pathways can be probed simultaneously, in real-time in the mouse liver in vivo using hyperpolarized DHAc.
Cancer Research UK (16465)
Cancer Research UK (CB4100)
Cancer Research UK (C14303_do not transfer)
External DOI: https://doi.org/10.1007/s10334-020-00884-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/309875
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