Multi-Frequency PARACEST Agents Based on Europium(III)-DOTA-Tetraamide Ligands
Multi-Frequency PARACEST Agents Based on Europium(III)-DOTA-Tetraamide Ligands
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DOI：
10.1002/anie.200904649
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
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作者：
Viswanathan, Subha;Ratnakar, S. James;Sherry, A. Dean
磁共振成像（MRI）是现代医学中最通用、最强大的诊断工具之一。最近，出现了一种基于化学交换饱和转移 (CEST) 的概念上不同的对比度增强方法，该方法利用两个或多个质子池 (kex≤ Δω) 之间的慢速到中速交换条件。 [1]虽然第一个报道的 CEST 试剂是含有可交换 NH 和 OH 基团 (Δω≤ 5 ppm) 的抗磁性分子，但后来表明，DOTA-四酰胺配体的某些顺磁性 Ln3+ 配合物的缓慢水交换特性允许选择性饱和超精细移动的 Ln3+ 结合水池 (Δω> 50 ppm)，以创建 CEST 对比度。 [2]顺磁系统中高位移交换共振的射频 (RF) 饱和比具有小 Δω 值的反磁 CEST 剂具有显着优势。[3]CEST 作为对比机制的主要优点之一是，只有在可交换质子的特定频率下施加 RF 脉冲时，才能检测到该效应。基于 Ln3+ 离子的 PARACEST（顺磁性 CEST）试剂在这方面特别有吸引力，因为跨镧系元素系列的不同离子可用于制备具有覆盖广泛频率范围的可交换质子的复合物。 Aime 及其同事使用基于 Eu3+ 和 Tb3+ 的 PARACEST 试剂精美地证明了多频 MRI 的原理证明。[4]诸如此类的“多频”PARACEST 试剂可用于同时对多个生物标志物进行成像，因为任何改变水交换动力学的参数（pH、温度、氧化还原、代谢物浓度）都会在
Magnetic resonance imaging (MRI) is one of the most versatile and powerful diagnostic tools in modern medicine. Recently, a conceptually different approach to contrast enhancement based on chemical exchange saturation transfer (CEST) has emerged that takes advantage of slow-to-intermediate exchange conditions between two or more pools of protons (kex≤ Δω).[1] While the first reported CEST agents were diamagnetic molecules containing exchangeable NH and OH groups (Δω≤ 5 ppm), it was later shown that the slow water exchange characteristics of certain paramagnetic Ln3+ complexes of DOTA-tetraamide ligands allows selective saturation of a hyperfine shifted Ln3+-bound water pool (Δω> 50 ppm) for creating CEST contrast.[2] Radio frequency (RF) saturation of highly shifted exchange resonances in paramagnetic systems offer significant advantages over diamagnetic CESTagents with small Δω values.[3]One of the primary advantages of CEST as a contrast mechanism is that the effect is detectable only when a RF pulse is applied at the specific frequency of the exchangeable protons. PARACEST (paramagnetic CEST) agents based on Ln3+ ions are particularly attractive in this respect because different ions across the lanthanide series can be used to prepare complexes with exchangeable protons covering a wide range of frequencies. The proof of principle for multi-frequency MRI was elegantly demonstrated by Aime and coworkers with Eu3+ and Tb3+-based PARACEST agents.[4]“Multi-frequency” PARACEST agents such as these could be useful in imaging multiple biomarkers simultaneously since any parameter (pH, temperature, redox, metabolite concentration) that alters the water exchange kinetics will in