Helmholtz Institute , Johannes Gutenberg University of Mainz , Mainz 55099 , Germany.
Department of Molecular Biotechnology and Health Sciences , University of Turin , Turin 10124 , Italy.
J Am Chem Soc. 2019 Dec 26;141(51):20209-20214. doi: 10.1021/jacs.9b10094. Epub 2019 Dec 10.
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]acetylene dicarboxylate with para-enriched hydrogen using a commercially available Ru catalyst in water to produce hyperpolarized [1-C]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 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]fumarate into cell suspensions and track the metabolism. This work opens the path to greatly accelerated preclinical studies using fumarate as a biomarker.
高极化延胡索酸盐可用作体内实时代谢的示踪剂，通过碳-13 磁共振成像进行检测。溶解动态核极化通常用于产生高极化延胡索酸盐，但更便宜、更快的替代方法是通过 PHIP（氘诱导极化）来产生高极化延胡索酸盐。在这项工作中，我们使用市售的 Ru 催化剂在水中将[1-C]乙炔二羧酸酯反氢化为高极化[1-C]延胡索酸盐。我们表明，延胡索酸盐以 89%的产率生成，琥珀酸盐以 11%的产率作为副产物生成。质子极化通过恒定绝热场循环转化为 C 磁化，使用 86%的氘富集氢气可实现 24%的极化水平。我们将高极化[1-C]延胡索酸盐注入细胞悬液中并追踪代谢情况。这项工作为使用延胡索酸盐作为生物标志物的大大加速临床前研究开辟了道路。
