Particle-based modelling of isotope exchange at equilibrium in hyperpolarized [1-13C]pyruvate MR

Motivation: Isotope exchange at equilibrium complicates interpretation hyperpolarized [1-13C]pyruvate MR. Modelling this phenomenon could help to quantify the effect of exchange on HP MR signal. Goal(s): Investigate how isotope exchange (compensatory backward conversion of unlabeled lactate concurrent with labeled lactate production) occurs and affects hyperpolarized [1-13C]pyruvate MR. Approach: Develop a realistic computational model of pyruvate-lactate interconversion and apply it to characterize how different levels of endogenous lactate influence metabolic reaction kinetics and exchange. Results: Elevation of unlabeled lactate increases isotope exchange at equilibrium. Net production of lactate occurs unless total lactate exceeds its equilibrium ratio with total pyruvate. Impact: This in silico model of isotope exchange in hyperpolarized [1-13C]pyruvate MR realistically replicates spectroscopic measurements, with particle-level data for a range of conditions providing insight into metabolic dynamics relevant to complex cellular architectures with different local equilibria.