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Imaging plays a crucial role in the early detection of HCC, although current methods are limited in their ability to characterize liver lesions. Most recently, deuterium metabolic imaging (DMI) has been demonstrated as a powerful technique for the imaging of metabolism in vivo. Here, we assess the metabolic flux of [6,6\u2032\u2010<jats:sup>2<\/jats:sup>H<jats:sub>2<\/jats:sub>] fructose in cell cultures and in subcutaneous mouse models at 9.4\u2009T. We compare these rates with the most widely used DMI probe, [6,6\u2032\u2010<jats:sup>2<\/jats:sup>H<jats:sub>2<\/jats:sub>] glucose, exploring the possibility of developing <jats:sup>2<\/jats:sup>H fructose to overcome the limitations of glucose as a novel DMI probe for detecting liver tumors. Comparison of the in vitro metabolic rates implies their similar glycolytic metabolism in the TCA cycle due to comparable production rates of <jats:sup>2<\/jats:sup>H glutamate\/glutamine (glx) for the two precursors, but overall higher glycolytic metabolism from <jats:sup>2<\/jats:sup>H glucose because of a higher production rate of <jats:sup>2<\/jats:sup>H lactate. In vivo kinetic studies suggest that HDO can serve as a robust reporter for the consumption of the precursors in liver tumors. As fructose is predominantly metabolized in the liver, deuterated water (HDO) produced from <jats:sup>2<\/jats:sup>H fructose is probably less contaminated from whole\u2010body metabolism in comparison with glucose. Moreover, in studies of the normal liver, <jats:sup>2<\/jats:sup>H fructose is readily converted to <jats:sup>2<\/jats:sup>H glx, enabling the characterization of <jats:sup>2<\/jats:sup>H fructose kinetics. This overcomes a major limitation of previous <jats:sup>2<\/jats:sup>H glucose studies in the liver, which were unable to confidently discern metabolic flux due to overlapped signals of <jats:sup>2<\/jats:sup>H glucose and its metabolic product, <jats:sup>2<\/jats:sup>H glycogen. This suggests a unique role for <jats:sup>2<\/jats:sup>H fructose metabolism in HCC and the normal liver, making it a useful approach for assessing liver\u2010related diseases and the progression to oncogenesis.<\/jats:p>","DOI":"10.1002\/nbm.4989","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T22:30:12Z","timestamp":1687213812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["[6,6\u2032\u2010<sup>2<\/sup>H<sub>2<\/sub>] fructose as a deuterium metabolic imaging probe in liver cancer"],"prefix":"10.1002","volume":"36","author":[{"given":"Guannan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiology Memorial Sloan Kettering Cancer Center  New York New York USA"},{"name":"Molecular Pharmacology Program Memorial Sloan Kettering Cancer Center  New York New York 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