基于 Para 氢诱导极化的延胡索酸盐代谢的 13C 磁共振成像:一项体内概念验证研究。

Hyperpolarized C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen-induced Polarization: A Proof-of-Concept in vivo Study.

机构信息

Division of Bioengineering & Bioinformatics, Graduate School of Information Science & Technology, Hokkaido University, North 14, West 9, Kita-ku, Sapporo, Hokkaido, 060-0814, Japan.

Division of Computational Chemistry, Transition State Technology Co. Ltd., 2-16-1 Tokiwadai, Ube, Yamaguchi, 755-8611, Japan.

出版信息

Chemphyschem. 2021 May 17;22(10):915-923. doi: 10.1002/cphc.202001038. Epub 2021 Mar 18.

Abstract

Hyperpolarized [1- 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- 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- 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- C]fumarate at sufficient C polarization for ex vivo detection of hyperpolarized C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo C MR spectroscopy and imaging in a murine model of acetaminophen-induced hepatitis.

摘要

1-13C 琥珀酸是一种很有前途的磁共振成像(MRI)细胞坏死生物标志物,在各种疾病和癌变过程中起着重要作用。为了证明使用 Para 氢诱导极化(PHIP)进行[1-13C]琥珀酸代谢 MRI 的可行性,开发了一种经济高效、高产的氢化前体[1-13C]丙炔二羧酸酯(ADC)的合成途径,这是溶解动态核极化(dDNP)的低成本替代方法。利用密度泛函理论(DFT)模拟阐明了使用基于钌的催化剂对 ADC 氢化反应的反选择性。使用简单的 PHIP 装置在足够的 C 极化下生成超极化[1-13C]琥珀酸,用于检测鼠肝组织匀浆中由琥珀酸代谢的超极化 13C 苹果酸,并在乙酰氨基酚诱导的肝炎的鼠模型中进行 13C MR 光谱和成像。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731e/8251594/badf2623b710/CPHC-22-915-g004.jpg

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