Multi-side kinetic model to assess [1-13C]pyruvate in-vivo metabolism

Hyperpolarized 13C imaging allows real-time in-vivo measurements of metabolic conversion. Experiments are performed by polarization of [1-13C]pyruvate with dynamic nuclear polarization and subsequent rapid dissolution, producing a hyperpolarized liquid suitable for intravenous injection. In a previous study we examined the metabolic exchange between [1-13C]pyruvate and its downstream metabolites [1-13C]alanine, [1-13C]lactate, [1-13C]pyruvate hydrate and [13C]bicarbonate in male Wistar rats by acquiring slice-selective FID signals in slices dominated by heart, liver, and kidney tissue. Using pyruvate doses of 0.1 - 0.4 mmol/kg (body mass), we examined the effect of transient exposure to high pyruvate blood concentrations, causing potential saturation of cellular uptake and metabolic conversion, semi-quantitatively using signal-time integrals. Further quantification of metabolite conversion can be achieved through kinetic modeling of time-domain signals. Present kinetic models represent a two-side interaction between pyruvate and one specific downstream metabolite. Since pyruvate interacts dynamically and simultaneously with all of the downstream metabolites, the purpose of this work is the determination of parameter values through a multi-side, dynamic model involving all possible biochemical pathways.     «

Hyperpolarized 13C imaging allows real-time in-vivo measurements of metabolic conversion. Experiments are performed by polarization of [1-13C]pyruvate with dynamic nuclear polarization and subsequent rapid dissolution, producing a hyperpolarized liquid suitable for intravenous injection. In a previous study we examined the metabolic exchange between [1-13C]pyruvate and its downstream metabolites [1-13C]alanine, [1-13C]lactate, [1-13C]pyruvate hydrate and [13C]bicarbonate in male Wistar rats by...     »