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无需外部偏振器的快速原位碳-13超极化以及乙酸酯和丙酮酸酯成像

Rapid in situ carbon-13 hyperpolarization and imaging of acetate and pyruvate esters without external polarizer.

作者信息

Mohiuddin Obaid, de Maissin Henri, Pravdivtsev Andrey N, Brahms Arne, Herzog Marvin, Schröder Leif, Chekmenev Eduard Y, Herges Rainer, Hövener Jan-Bernd, Zaitsev Maxim, von Elverfeldt Dominik, Schmidt Andreas B

机构信息

Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Killianstr. 5a, 79106, Freiburg, Germany.

German Cancer Consortium (DKTK), partner site Freiburg, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.

出版信息

Commun Chem. 2024 Oct 23;7(1):240. doi: 10.1038/s42004-024-01316-x.

DOI:10.1038/s42004-024-01316-x
PMID:39443619
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11499913/
Abstract

Hyperpolarized C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-C]acetate and [1-C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P ≈ 28% at 80 mM concentration and P ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where C MRI is performed. We exemplified the utility of the design with sub-second in situ C MRI of ethyl [1-C]pyruvate-d. However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized C MRI.

摘要

超极化碳磁共振成像(MRI)可在体内可视化实时代谢过程。在本研究中,我们在MRI系统的磁孔内原位实现了对最广泛使用的超极化剂的前体分子的高碳极化:[1-¹³C]乙酸盐和[1-¹³C]丙酮酸乙酯的全氘代形式,延长了超极化寿命,在80 mM浓度下超极化至P≈28%,在10 mM浓度下超极化至P≈19%。使用乙烯基酯作为通过侧链氢化实现的不饱和仲氢诱导极化(PHIP-SAH)前体以及我们新颖的极化装置,我们通过在丙酮-d中高温(高达90°C)和氢化压力(高达32 bar)下的快速侧链氢化实现了这些超极化水平。我们优化了超极化过程,将其缩短至10秒以内,并采用先进的脉冲序列来提高极化转移效率。该超极化系统占地面积小,可放置在进行碳MRI的同一磁体中。我们以[1-¹³C]丙酮酸乙酯-d的亚秒级原位碳MRI为例展示了该设计的实用性。然而,在MRI系统中进行侧链裂解和纯化以提取高极化水性剂溶液仍存在挑战。我们的结果展示了在MRI系统中以最少的额外硬件对这些代谢物前体进行高效快速的碳超极化,有望提高未来超极化碳MRI的通量和可及性。

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Anal Chem. 2024 Mar 12;96(10):4171-4179. doi: 10.1021/acs.analchem.3c05233. Epub 2024 Feb 15.
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Quo Vadis Hyperpolarized C MRI?超极化碳磁共振成像何去何从?
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New Horizons in Hyperpolarized C MRI.超极化 C MRI 的新视野。
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Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-C]pyruvate in vivo.用于体内[1-C]丙酮酸分子成像和代谢追踪的简便超极化化学方法。
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Exceptionally Mild and High-Yielding Synthesis of Vinyl Esters of Alpha-Ketocarboxylic Acids, Including Vinyl Pyruvate, for Parahydrogen-Enhanced Metabolic Spectroscopy and Imaging.α-酮羧酸乙烯酯的异常温和高产合成,包括丙酮酸乙烯酯,用于增强氢代谢的光谱和成像。
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Molecular precursors to produce para-hydrogen enhanced metabolites at any field.在任何磁场下产生仲氢增强代谢物的分子前体。
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