Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution.
Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution.
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DOI：
10.1073/pnas.2025383118
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发表时间：
2021-03-30
影响因子：
11.1
通讯作者：
Eills J
中科院分区：
文献类型：
--
作者：
Knecht S;Blanchard JW;Barskiy D;Cavallari E;Dagys L;Van Dyke E;Tsukanov M;Bliemel B;Münnemann K;Aime S;Reineri F;Levitt MH;Buntkowsky G;Pines A;Blümler P;Budker D;Eills J
磁共振成像受到固有的低灵敏度的阻碍，这限制了该方法的大部分观察体内的水分子。超极化分子表现出强烈增强的MRI信号，这为体内低浓度物质的成像打开了大门。生物分子可以被超极化并注射到患者体内，从而允许真实的时间跟踪代谢，极大地扩展了放射科医生可用的信息。仲氢诱导极化（PHIP）是一种超极化方法，以其低成本和可获得性而闻名，但通常受到低极化水平，适度分子浓度和极化试剂污染的限制。在这项工作中，我们克服了PHIP极化[1- 13 C]富马酸盐生产中的这些缺点，富马酸盐是代谢13 C MRI中细胞坏死的生物标志物。超极化富马酸盐是一种很有前途的碳13磁共振代谢成像生物传感器。这种分子成像应用需要核超极化以获得足够的信号强度。溶出动态核极化是目前最先进的超极化富马酸盐的方法，但这是昂贵的和相对缓慢的。或者，这种重要的生物分子可以使用仲氢诱导的极化以便宜且方便的方式超极化。然而，该方法需要化学反应，并且所得溶液被催化剂、未反应的试剂和反应副产物分子污染，因此不适合在体内使用。在这项工作中，我们表明，超极化的富马酸盐可以从这些污染物中纯化的酸沉淀作为一个纯固体，后来重新溶解到一个干净的水溶剂中所需的浓度。反应条件和反应器设备的显著进步允许在30- 45%的13 C极化水平下形成超极化富马酸盐。
Magnetic resonance imaging is hindered by inherently low sensitivity, which limits the method for the most part to observing water molecules in the body. Hyperpolarized molecules exhibit strongly enhanced MRI signals which opens the door for imaging low-concentration species in vivo. Biomolecules can be hyperpolarized and injected into a patient allowing for metabolism to be tracked in real time, greatly expanding the information available to the radiologist. Parahydrogen-induced polarization (PHIP) is a hyperpolarization method renowned for its low cost and accessibility, but is generally limited by low polarization levels, modest molecular concentrations, and contamination by polarization reagents. In this work we overcome these drawbacks in the production of PHIP-polarized [1-13C]fumarate, a biomarker of cell necrosis in metabolic 13C MRI. Hyperpolarized fumarate is a promising biosensor for carbon-13 magnetic resonance metabolic imaging. Such molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting solutions are contaminated with the catalyst, unreacted reagents, and reaction side-product molecules, and are hence unsuitable for use in vivo. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved to a desired concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow for formation of hyperpolarized fumarate at 13C polarization levels of 30–45%.
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影响因子：
5.7
作者：
Bohndiek SE;Kettunen MI;Hu DE;Witney TH;Kennedy BW;Gallagher FA;Brindle KM
通讯作者：
Brindle KM
影响因子：
4.6
作者：
Cavallari E;Carrera C;Sorge M;Bonne G;Muchir A;Aime S;Reineri F
通讯作者：
Reineri F
DOI：
10.1073/pnas.1205539109
发表时间：
2012-08-14
影响因子：
11.1
作者：
Clatworthy, Menna R.;Kettunen, Mikko I.;Brindle, Kevin M.
通讯作者：
Brindle, Kevin M.
DOI：
10.1002/asia.201800551
发表时间：
2018-05-23
期刊：
Chemistry, an Asian journal
影响因子：
--
作者：
Kovtunov KV;Pokochueva EV;Salnikov OG;Cousin SF;Kurzbach D;Vuichoud B;Jannin S;Chekmenev EY;Goodson BM;Barskiy DA;Koptyug IV
通讯作者：
Koptyug IV
影响因子：
15
作者：
Eills, James;Cavallari, Eleonora;Reineri, Francesca
通讯作者：
Reineri, Francesca