Hyperpolarized 13 C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen‐induced Polarization: A Proof‐of‐Concept in vivo Study
| Autor: | Shingo Matsumoto, Hiroshi Hirata, Mitsushi Tomohiro, Yujirou Matsuo, Yuki Kase, Shuto Sugai, Tatsuya Naganuma, Neil J. Stewart, Hitomi Nakano, Norihiko Takeda, Ikuya Nishimura, Toru Yamaguchi, Yoshiki Uchio, Takuya Hashimoto |
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| Rok vydání: | 2021 |
| Předmět: |
In vivo magnetic resonance spectroscopy
Acetylenedicarboxylate chemistry.chemical_element 02 engineering and technology 010402 general chemistry Spin isomers of hydrogen 01 natural sciences Article Nuclear magnetic resonance Fumarates matabolism In vivo medicine Physical and Theoretical Chemistry Density Functional Theory Carbon Isotopes fumarate medicine.diagnostic_test Chemistry hyperpolarized C-13 MRS/I Magnetic resonance imaging Articles 021001 nanoscience & nanotechnology Magnetic Resonance Imaging In vitro Atomic and Molecular Physics and Optics 0104 chemical sciences Ruthenium Alkynes parahydrogen-induced polarization density functional calculations Fatty Acids Unsaturated Hydrogenation 0210 nano-technology Selectivity hyperpolarized 13C MRS/I |
| Zdroj: | Chemphyschem |
| ISSN: | 1439-7641 1439-4235 |
| DOI: | 10.1002/cphc.202100338 |
| Popis: | Hyperpolarized [1‐13C]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 [1‐13C]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 [1‐13C]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 [1‐13C]fumarate at sufficient 13C polarization for ex vivo detection of hyperpolarized 13C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo 13C MR spectroscopy and imaging in a murine model of acetaminophen‐induced hepatitis. Toward clinical translation: Hyperpolarized [1‐13C]fumarate was prepared by the trans‐selective para‐hydrogenation of [1‐13C] acetylenedicarboxylate precursor using a [Cp*Ru(MeCN)3]PF6 catalyst. The feasibility of in vivo imaging of necrotic cell death by 13C MRI of PHIP‐hyperpolarized exogenously injected fumarate metabolism was demonstrated in an acetaminophen‐induced hepatitis mouse. |
| Databáze: | OpenAIRE |
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