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Hyperpolarized 13 C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen‐induced Polarization: A Proof‐of‐Concept in vivo Study
Author(s) -
Stewart Neil J.,
Nakano Hitomi,
Sugai Shuto,
Tomohiro Mitsushi,
Kase Yuki,
Uchio Yoshiki,
Yamaguchi Toru,
Matsuo Yujirou,
Naganuma Tatsuya,
Takeda Norihiko,
Nishimura Ikuya,
Hirata Hiroshi,
Hashimoto Takuya,
Matsumoto Shingo
Publication year - 2021
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.202001038
Subject(s) - chemistry , in vivo , spin isomers of hydrogen , hyperpolarization (physics) , nuclear magnetic resonance spectroscopy , nuclear magnetic resonance , dimethyl fumarate , stereochemistry , organic chemistry , medicine , physics , microbiology and biotechnology , psychiatry , multiple sclerosis , biology , hydrogen
Hyperpolarized [1‐ 13 C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1‐ 13 C]fumarate metabolism using parahydrogen‐induced polarization (PHIP), a low‐cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost‐effective and high‐yield synthetic pathway of hydrogenation precursor [1‐ 13 C]acetylenedicarboxylate (ADC) was developed. The trans ‐selectivity of the hydrogenation reaction of ADC using a ruthenium‐based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set‐up was used to generate hyperpolarized [1‐ 13 C]fumarate at sufficient 13 C polarization for ex vivo detection of hyperpolarized 13 C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo 13 C MR spectroscopy and imaging in a murine model of acetaminophen‐induced hepatitis.