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通过可逆交换实现信号放大,从而获得高 H 核超极化水平和长磁寿命。

Delivering strong H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange.

作者信息

Rayner Peter J, Burns Michael J, Olaru Alexandra M, Norcott Philip, Fekete Marianna, Green Gary G R, Highton Louise A R, Mewis Ryan E, Duckett Simon B

机构信息

Centre for Hyperpolarisation in Magnetic Resonance, Department of Chemistry, University of York, Heslington YO10 5NY, United Kingdom.

Centre for Hyperpolarisation in Magnetic Resonance, Department of Chemistry, University of York, Heslington YO10 5NY, United Kingdom

出版信息

Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3188-E3194. doi: 10.1073/pnas.1620457114. Epub 2017 Apr 4.

Abstract

Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost hydrogen-based approach signal amplification by reversible exchange with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific H labeling in both the agent and catalyst and achieve polarization lifetimes of 2 min with 50% polarization in the case of methyl-4,6- -nicotinate. Because a 1.5-T hospital scanner has an effective H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this technique's generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine, and isonicotinamide analogs that feature as building blocks in biochemistry and many disease-treating drugs.

摘要

超极化通常会将微弱的核磁共振(NMR)和磁共振成像(MRI)信号转变为强信号,从而使通常不切实际的测量变得可行。通过这种方法彻底改变分析性核磁共振和临床诊断的潜力反映了该领域最引人注目的成果。详细介绍了通过与一系列具有生物学相关性的烟酰胺和甲基烟酸酯进行可逆交换来优化低成本氢基方法信号放大的方法。这些程序涉及在试剂和催化剂中进行特定的氢标记,对于甲基-4,6-烟酸酯,可实现2分钟的极化寿命和50%的极化率。由于1.5-T医院扫描仪的有效氢极化水平仅为0.0005%,因此该策略应能缩短用于探测疾病的化学鉴别测量的检测时间。为了证明该技术的通用性,我们举例说明了对一系列哒嗪、嘧啶、吡嗪和异烟酰胺类似物的进一步研究,这些类似物是生物化学和许多疾病治疗药物中的组成部分。

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