Real-Time Nuclear Magnetic Resonance Detection of Fumarase Activity Using Parahydrogen-Hyperpolarized [1-13C]Fumarate
Real-Time Nuclear Magnetic Resonance Detection of Fumarase Activity Using Parahydrogen-Hyperpolarized [1-13C]Fumarate
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DOI：
10.1021/jacs.9b10094
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发表时间：
2019-12-25
影响因子：
15
通讯作者：
Reineri, Francesca
中科院分区：
文献类型：
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作者：
Eills, James;Cavallari, Eleonora;Reineri, Francesca
利用碳-13磁共振成像技术，超极化富马酸盐可以作为体内实时代谢的探针。溶解动态核极化通常用于生产超极化富马酸盐，但一种更便宜和更快的替代方法是通过PHIP（副氢诱导极化）生产超极化富马酸盐。在这项工作中，我们使用一种市售的Ru催化剂在水中用对富集氢反式加氢[1-C-13]乙炔二羧酸盐，以生产超极化的[1-C-13]富马酸盐。我们发现富马酸盐的产率为89%，琥珀酸盐作为副产品的产率为11%。利用恒定绝热场循环将质子极化转化为C-13磁化，在86%的para-富集氢气中实现了24%的极化水平。我们将超极化的[1-C-13]富马酸酯注入细胞悬液中并跟踪其代谢。这项工作为使用富马酸作为生物标志物的临床前研究开辟了道路。
Hyperpolarized fumarate can be used as a probe of real-time metabolism in vivo, using carbon-13 magnetic resonance imaging. Dissolution dynamic nuclear polarization is commonly used to produce hyperpolarized fumarate, but a cheaper and faster alternative is to produce hyperpolarized fumarate via PHIP (parahydrogen-induced polarization). In this work, we trans hydrogenate [1-C-13]acetylene dicarboxylate with para-enriched hydrogen using a commercially available Ru catalyst in water to produce hyperpolarized [1-C-13]fumarate. We show that fumarate is produced in 89% yield, with succinate as a side product in 11% yield. The proton polarization is converted into C-13 magnetization using a constant adiabaticity field cycle, and a polarization level of 24% is achieved using 86% para-enriched hydrogen gas. We inject the hyperpolarized [1-C-13]fumarate into cell suspensions and track the metabolism. This work opens the path to greatly accelerated preclinical studies using fumarate as a biomarker.