title: Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model.
abstract: 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 T1Eff 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 (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-(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.
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Flori
authors.affiliation: Department of Physics, University of Pisa, Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Liserani
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Frijia
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.|Institute of Clinical Physiology, National Council of Research, Pisa, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Giovannetti
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Casieri
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Positano
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Giovanni Donato
authors.initials: GD
authors.lastname: Aquaro
authors.affiliation: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.|Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.|Institute of Clinical Physiology, National Council of Research, Pisa, Italy.
authors.forename: Maria Filomena
authors.initials: MF
authors.lastname: Santarelli
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.|Department of Information Engineering, University of Pisa, Pisa, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Landini
authors.affiliation: GE Healthcare, Broendby, Denmark.|Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Ardenkjaer-Larsen
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy.|Institute of Clinical Physiology, National Council of Research, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Menichetti
mesh_terms: D000108:Acetylcarnitine / Q000096:biosynthesis; D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D019346:Sodium Acetate / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
chemical_list: D002247:Carbon Isotopes; D005230:Fatty Acids, Nonesterified; D019346:Sodium Acetate; D000108:Acetylcarnitine
keywords: [1-13C]acetate; [1-13C]acetyl-carnitine; dynamic nuclear polarization (DNP); free fatty acid (FA) metabolism; heart metabolism; hyperpolarization; magnetic resonance spectroscopy (MRS); trityl radical