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 Na[1-13C]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 Na[1-13C]acetate formulation was characterized by a liquid-state polarization of 14.2% and a T1Eff in vivo of 17.6 ± 1.7 s. In vivo Na[1-13C]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 (kAcC), 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