Real‐time cardiac metabolism assessed with hyperpolarized [1‐ 13 C]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‐ 13 C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution‐DNP procedure of Na[1‐ 13 C]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 Na[1‐ 13 C]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 Na[1‐ 13 C]acetate kinetics displayed a bimodal shape: [1‐ 13 C]acetyl carnitine (AcC) was detected in a slice covering the cardiac volume, and the signal of 13 C‐acetate and 13 C‐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‐ 13 C]acetate to [1‐ 13 C]AcC (k AcC ), divided by the AcC longitudinal relaxation rate (r 1 ). Our study proved the feasibility and the limitations of administration of large doses of hyperpolarized [1‐ 13 C]acetate to study the myocardial conversion of [1‐ 13 C]acetate in [1‐ 13 C]acetyl‐carnitine generated by acetyltransferase in healthy pigs. Copyright © 2014 John Wiley & Sons, Ltd.