Real‐time cardiac metabolism assessed with hyperpolarized [1‐13C]acetate in a large‐animal model

Dissolution‐dynamic nuclear polarization (dissolution‐DNP) for magnetic resonance (MR) spectroscopic imaging has recently emerged as a novel technique for noninvasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra‐ and intracellular short‐chain fatty acid, we focused on 1‐¹³C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution‐DNP procedure of Na1‐¹³C]acetate for in vivo cardiac applications with a 3 T MR scanner was optimized in pigs during bolus injection of doses of up to 3 mmol. The Na1‐¹³C]acetate formulation was characterized by a liquid‐state polarization of 14.2% and a T_1Eff in vivo of 17.6 ± 1.7 s. In vivo Na1‐¹³C]acetate kinetics displayed a bimodal shape: 1‐¹³C]acetyl carnitine (AcC) was detected in a slice covering the cardiac volume, and the signal of ¹³C‐acetate and ¹³C‐AcC was modeled using the total area under the curve (AUC) for kinetic analysis. A good correlation was found between the ratio AUC(AcC)/AUC(acetate) and the apparent kinetic constant of metabolic conversion, from 1‐¹³C]acetate to 1‐¹³C]AcC (k_AcC), divided by the AcC longitudinal relaxation rate (r₁). Our study proved the feasibility and the limitations of administration of large doses of hyperpolarized 1‐¹³C]acetate to study the myocardial conversion of 1‐¹³C]acetate in 1‐¹³C]acetyl‐carnitine generated by acetyltransferase in healthy pigs. Copyright © 2014 John Wiley & Sons, Ltd.