Kinetic Modeling of HP [1-13C]-Pyruvate Determines Dominant Physiological Parameters Influencing Lactate to Pyruvate AUC Ratio

Motivation: The translation of HP [1-13C]-pyruvate as a method for quantifying aerobic glycolysis in tumors depends on a careful analysis of the processes that drive lactate production. Goal(s): We seek to introduce a method to determine the rate-limiting steps in overall lactate production. Approach: The HP pyruvate study of a patient with oropharyngeal squamous cell carcinoma was reanalyzed with pharmacokinetic modeling to determine relative levels of HP pyruvate in the three physical compartments of a pharmacokinetic model. Results: Overall pyruvate signal was mostly dominated by extravascular/extracellular pyruvate, indicating that lactate production was not primarily influenced by intracellular metabolism. Impact: The proposed analysis has the potential to aid in the analysis of [1-13C]-pyruvate studies by distinguishing between the effects of pyruvate delivery to the cells and true Warburg metabolism in tumors.