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

Alessandra Flori, Matteo Liserani, Francesca Frijia, Giulio Giovannetti, Vincenzo Lionetti, Valentina Casieri, Vincenzo Positano, Giovanni Donato Aquaro, Fabio A. Recchia, Maria Filomena Santarelli, Luigi Landini, Jan Henrik Ardenkjær-Larsen, Luca Menichetti

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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 [1-13C]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
Original languageEnglish
JournalContrast Media & Molecular Imaging
Volume10
Issue number3
Pages (from-to)194–202
ISSN1555-4309
DOIs
Publication statusPublished - 2015

Keywords

  • Hyperpolarization
  • Dynamic nuclear polarization (DNP)
  • Magnetic resonance spectroscopy (MRS)
  • Free fatty acid (FA) metabolism
  • Trityl radical
  • [1- 13 C]acetyl-carnitine
  • [1- 13 C]acetate
  • Heart metabolism

Cite this

Flori, A., Liserani, M., Frijia, F., Giovannetti, G., Lionetti, V., Casieri, V., Positano, V., Aquaro, G. D., Recchia, F. A., Santarelli, M. F., Landini, L., Ardenkjær-Larsen, J. H., & Menichetti, L. (2015). Real-time cardiac metabolism assessed with hyperpolarized [1-13C]acetate in a large-animal model. Contrast Media & Molecular Imaging, 10(3), 194–202. https://doi.org/10.1002/cmmi.1618