Paramagnetic lanthanide(III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications

Paramagnetic lanthanide(III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications
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顺磁性镧系元素 (III) 配合物作为 MRI 应用的 pH 敏感化学交换饱和转移 (CEST) 造影剂

DOI:
10.1002/mrm.10106
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发表时间:
2002-04-01
影响因子:
3.3
通讯作者:
Terreno, E
Terreno, E
中科院分区:
医学3区
文献类型:
--
作者:
Aime, S;Barge, A;Terreno, E

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The recently introduced new class of contrast agents (CAs) based on chemical exchange saturation transfer (CEST) may have a huge potential for the development of novel applications in the field of MRI. In this work we explored the CEST properties of a series of Lanthanide(III) complexes (Ln = Eu, Dy, Ho, Er, Tm, Yb) with the macrocyclic DOTAM-Gly ligand, which is the tetraglycineamide derivative of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). These complexes possess two pools of exchangeable protons represented by the coordinated water and the amide protons. Yb-DOTAM-Gly disc plays the most interesting CEST properties when its amide N-H resonance (16 ppm upfield H2O signal) is irradiated. Up to 70% suppression of the water signal is obtained at pH 8. As the exchange rate of amide protons is base-catalyzed, Yb-DOTAM-Gly results to be an efficient pH-responsive probe in the 5.5-8.1 pH range. Moreover, a ratiometric method has been set up in order to remove the dependence of the observed pH responsiveness from the absolute concentration of the paramagnetic agent. In fact, the use of a mixture of Eu-DOTAM-Gly and Yb-DOTAM-Gly, whose exchangeable proton pools are represented by the coordinated water (ca. 40 ppm downfield H2O signal at 312K) and amide protons, respectively, produces a pH-dependent CEST effect which is the function of the concentration ratio of the two complexes. 2002. (C) 2002 Wiley-Liss, Inc.