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用于体内实时代谢成像的无稳定自由基的超极化。

Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging.

机构信息

Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.

出版信息

Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18064-9. doi: 10.1073/pnas.1314928110. Epub 2013 Oct 21.

Abstract

Hyperpolarized substrates prepared via dissolution dynamic nuclear polarization have been proposed as magnetic resonance imaging (MRI) agents for cancer or cardiac failure diagnosis and therapy monitoring through the detection of metabolic impairments in vivo. The use of potentially toxic persistent radicals to hyperpolarize substrates was hitherto required. We demonstrate that by shining UV light for an hour on a frozen pure endogenous substance, namely the glucose metabolic product pyruvic acid, it is possible to generate a concentration of photo-induced radicals that is large enough to highly enhance the (13)C polarization of the substance via dynamic nuclear polarization. These radicals recombine upon dissolution and a solution composed of purely endogenous products is obtained for performing in vivo metabolic hyperpolarized (13)C MRI with high spatial resolution. Our method opens the way to safe and straightforward preclinical and clinical applications of hyperpolarized MRI because the filtering procedure mandatory for clinical applications and the associated pharmacological tests necessary to prevent contamination are eliminated, concurrently allowing a decrease in the delay between preparation and injection of the imaging agents for improved in vivo sensitivity.

摘要

通过溶解动态核极化制备的超极化底物已被提议作为磁共振成像 (MRI) 剂,用于癌症或心力衰竭的诊断和治疗监测,通过检测体内代谢损伤。 以前需要使用潜在有毒的持久性自由基来极化底物。 我们证明,通过在冷冻的纯内源性物质(即葡萄糖代谢产物丙酮酸)上照射一小时的紫外线,有可能产生足够大的光诱导自由基浓度,通过动态核极化来高度增强物质的 (13)C 极化。 这些自由基在溶解时重新组合,得到仅由内源性产物组成的溶液,可用于进行具有高空间分辨率的体内代谢超极化 (13)C MRI。 我们的方法为安全、直接的临床前和临床应用的超极化 MRI 开辟了道路,因为临床应用所必需的过滤过程和为防止污染所需的相关药理学测试被消除,同时允许在准备和注射成像剂之间的延迟减少,以提高体内敏感性。

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