Hyperpolarized [2-13C]pyruvate-d3 detects hepatic gluconeogenesis in vivo

Motivation: Assessing gluconeogenesis using hyperpolarized [1-13C]pyruvate is technically challenging because [13C]bicarbonate can be produced from both oxidative and gluconeogenic pathways and spectrally resolving the gluconeogenic products from large, neighboring peaks is non-trivial at 3T. Goal(s): This study examines the utility of deuterated hyperpolarized [2-13C]pyruvate in assessing gluconeogenesis. Approach: Sodium [2-13C]pyruvate-d3 was synthesized to prolong the T1. Hepatic metabolism was investigated using hyperpolarized [2-13C]pyruvate-d3with D2O dissolution under normal fed and fasted conditions. Results: The T1 of [2-13C]pyruvate-d3 was ~80 s when dissolved with D2O. Gluconeogenic products such as [2-13C]oxaloacetate and [2-13C]phosphoenolpyruvate were observed from fasted rats only, highlighting clear advantages over [1-13C]pyruvate in investigating gluconeogenesis. Impact: Hyperpolarization technology is rapidly being translated to humans. With the proven safety and feasibility, hyperpolarized [2-13C]pyruvate-d3 will facilitate its utilization in underexplored liver and kidney metabolism, illuminating mechanistic understanding for several disorders that are believed to depend on altered gluconeogenesis.