Oxidation of hyperpolarized [1-C-13]pyruvate in isolated rat kidneys

Kidneys play a central role in numerous disorders but current imaging methods have limited utility to probe renal metabolism. Hyperpolarized (HP) C-13 magnetic resonance imaging is uniquely suited to provide metabolite-specific information about key biochemical pathways and it offers the further advantage that renal imaging is practical in humans. This study evaluated the feasibility of hyperpolarization examinations in a widely used model for analysis of renal physiology, the isolated kidney, which enables isolation of renal metabolism from the effects of other organs and validation of HP results by independent measurements. Isolated rat kidneys were supplied with either HP [1-C-13]pyruvate only or HP [1-C-13]pyruvate plus octanoate. Metabolic activity in both groups was confirmed by stable renal oxygen consumption. HP [1-C-13]pyruvate was readily metabolized to [C-13]bicarbonate, [1-C-13]lactate, and [1-C-13]alanine, detectable seconds after HP [1-C-13]pyruvate was injected. Octanoate suppressed but did not eliminate the production of HP [C-13]bicarbonate from [1-C-13]pyruvate. Steady-state flux analyses using non-HP C-13 substrates validated the utilization of HP [1-C-13]pyruvate, as observed by HP C-13 NMR. In the presence of octanoate, lactate is generated from a tricarboxylic acid cycle intermediate, oxaloacetate. The isolated rat kidney may serve as an excellent model for investigating and establishing new HP C-13 metabolic probes for future kidney imaging applications.