Probing carbohydrate metabolism using hyperpolarized 13 C-labeled molecules

Abstract

Glycolysis is a fundamental metabolic process in all organisms. Anomalies in glucose metabolism are linked to various pathological conditions. In particular, elevated aerobic glycolysis is a characteristic feature of rapidly growing cells. Glycolysis and the closely related pentose phosphate pathway can be monitored in real time by hyperpolarized ¹³ C-labeled metabolic substrates such as ¹³ C-enriched, deuterated D-glucose derivatives, [2-¹³ C]-D-fructose, [2-¹³ C] dihydroxyacetone, [1-¹³ C]-D-glycerate, [1-¹³ C]-D-glucono-δ-lactone and [1-¹³ C] pyruvate in healthy and diseased tissues. Elevated glycolysis in tumors (the Warburg effect) was also successfully imaged using hyperpolarized [U-¹³ C₆ , U-² H₇ ]-D-glucose, while the size of the preexisting lactate pool can be measured by ¹³ C MRS and/or MRI with hyperpolarized [1-¹³ C]pyruvate. This review summarizes the application of various hyperpolarized ¹³ C-labeled metabolites to the real-time monitoring of glycolysis and related metabolic processes in normal and diseased tissues.

Keywords: dynamic nuclear polarization; glycolysis; hyperpolarized 13C NMR; metabolic probes.