Production of highly polarized [1‐¹³C]acetate by rapid decarboxylation of [2‐¹³C]pyruvate – application to hyperpolarized cardiac spectroscopy and imaging

Abstract

Purpose:The objective of the present work was to develop and implement an efficient approach to hyperpolarize [1-13 C]acetate and apply it to in vivo cardiac spectroscopy and imaging. Methods: Rapid hydrogen peroxide induced decarboxylation was used to convert hyperpolarized [2-13 C]pyruvate into highly polarized [1-13 C]acetate employing an additional step following rapid dissolution of [2-13 C]pyruvate in a home-built multisample dissolution dynamic nuclear polarization system. Phantom dissolution experiments were conducted to determine optimal parameters of the decarboxylation reaction, retaining polarization and T 1 of [1-13 C]acetate. In vivo feasibility of detecting [1-13 C]acetate metabolism is demonstrated using slice-selective spectroscopy and multi-echo imaging of [1-13 C]acetate and [1-13 C]acetylcarnitine in the healthy rat heart. Results: The first in vivo signal was observed ~23 s after dissolution. At the corresponding time point in the phantom experiments, 97.9 ± 0.4% of [2-13 C]pyruvate were converted into [1-13 C]acetate by the decarboxylation reaction. T 1 and polarization of [1-13 C]acetate was determined to be 29.7 ± 1.9% and a 47.7 ± 0.5 s.Polarization levels of [2-13 C]pyruvate and [1-13 C]acetate were not significantly different after transfer to the scanner. In vivo, [1-13 C]acetate and [1-13 C]acetylcarnitine could be detected using spectroscopy and imaging. Conclusion: Decarboxylation of hyperpolarized [2-13 C]pyruvate enables the efficient production of highly polarized [1-13 C]acetate that is applicable to study shortchain fatty acid metabolism in the in vivo heart. K E Y W O R D Sacetate, cardiac metabolism, DNP, dynamic nuclear polarisation, hyperpolarized 13C | INTRODUCTIONAdenosine triphosphate (ATP), the energy currency of the eukaryotic cell, is derived via 2 main pathways-mitochondrial metabolism, accounting for 95% of the generated ATP and glycolytic energy generation. Among various substrates, fatty acids and carbohydrates constitute the main sources of energy with fatty acids accounting for 70-90% of the energy supply ORCID Jonas Steinhauserhttps://orcid.org/0000-0003-3916-1285Patrick Wespi https://orcid.org/0000-0003-4309-445XGrzegorz Kwiatkowski