Dissolution-Dynamic Nuclear Polarization (dissolution-DNP) for Magnetic Resonance (MR) Spectroscopic Imaging has recently emerged as a novel technique for non invasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra- and intra-cellular short-chain fatty acid, we focused on [1-13C]acetate as a promising candidate for a chemical probe to study myocardial metabolism of beating heart. Dissolution-DNP procedure of Na[1-13C]acetate for in vivo cardiac applications with 3T MR scanner was optimized in pigs during bolus injection of doses up to 3 mmoles. The Na[1-13C]acetate formulation was characterized by a liquid-state polarization of 14.2% and T1Eff in vivo of 17.6 ± 1.7 s. In vivo Na[1-13C]acetate kinetic 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 kAcC/r1 from [1-13C]acetate to [1-13C]AcC. Our study proved the feasibility and limitations of administration of large doses of hyperpolarized [1-13C]acetate with dissolution DNP to study by MR spectroscopy the myocardial conversion of [1-13C]acetate in [1-13C]acetyl-carnitine generated by acetyltransferase in healthy pigs.

The intrinsic physicochemical properties of the sample formulation are the key factors for efficient hyperpolarization through dissolution dynamic nuclear polarization (dissolution-DNP). We provide a comprehensive characterization of the DNP process for Na-[1-(13)C]acetate selected as a model for non-self-glassing agents: the solid-state polarization dynamics of different formulations and the effect of the paramagnetic agent (trityl radical) on the pattern of polarization and the relaxation profile were extensively analyzed. We quantified the effects of the glassing agent and Gd(3+)-chelate on DNP performance. The results reported here describe the constraints of the acetate formulation useful for future studies in this field with non-self-glassing enriched molecules.

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