Simultaneous investigation of cardiac pyruvate dehydrogenase flux Krebs cycle metabolism and pH using hyperpolarized 12-13C2pyruvate in vivo

摘要

¹³C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of pre-polarized [1-¹³C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the ¹³C label must be placed on the C2 position of pyruvate. Thus the utilization of either C1 or C2 labeled pre-polarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the pre-polarized pyruvate molecules were labeled at both C1 and C2 position, then it would be possible to observe the downstream metabolites that were the results of both PDH flux (¹³CO2 and H¹³CO3⁻) and Krebs cycle flux ([5-¹³C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the ¹³CO2 resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve ¹³CO2 detection, the feasibility of using dual-labeled hyperpolarized [1,2-¹³C2]pyruvate as a substrate for dynamic cardiac metabolic MRS studies, to allow simultaneous investigation of PDH flux, Krebs cycle flux, and pH was demonstrated in vivo.