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使用具有大有效磁矩的Ln(3+)配合物Tm(3+)-HPDO3A在1T下进行的MRI CEST:一种高效的MRI pH报告剂。

MRI CEST at 1T with large µeff Ln(3+) complexes T m(3+)-HPDO3A: An efficient MRI pH reporter.

作者信息

Rancan Giaime, Delli Castelli Daniela, Aime Silvio

机构信息

Technical University Munich, Klinikum rechts der Isar, München, Germany.

University of Turin, Molecular Imaging Center, Torino, Italy.

出版信息

Magn Reson Med. 2016 Jan;75(1):329-36. doi: 10.1002/mrm.25589. Epub 2015 Feb 4.

DOI:10.1002/mrm.25589
PMID:25651986
Abstract

PURPOSE

Chemical exchange saturation transfer (CEST) sensitivity relies on the prototropic exchange rate kex between the agent and the "bulk" water protons. To exploit large kex, a large frequency separation (Δω) between the pools of exchanging protons is necessary. For this reason, high magnetic fields are preferred. Herein it is shown that the use of paramagnetic CEST agents based on lanthanide (III) ions with large effective magnetic moments allows the carrying out of CEST experiments at the relatively low field strength of 1 tesla (T).

METHODS

Measurements were performed on a 1T MR-scanner using continuous wave (cw)-presaturation with a spin echo sequence. ParaCEST complexes have been synthetized by mixing the ligand and Ln(III)Cl3 in a stoichiometric ratio at room temperature and pH 7.

RESULTS

Different lanthanide chelates were investigated (Tm-, Dy-, Yb-, Eu-HPDO3A, and Eu-DOTAMGly). Ratiometric (Tm-HPDO3A) and selective detection (Eu-DOTAMGly and Tm-HPDO3A) experiments have been proven feasible in vivo.

CONCLUSION

In vitro experiments demonstrated the feasibility of the CEST methodology at 1T for nearly every paraCEST candidate under investigation, except for Eu-HPDO3A. Among the studied compounds, Tm-HPDO3A proved suitable for the application of a ratiometric method for assessing pH both in vitro and in vivo.

摘要

目的

化学交换饱和转移(CEST)灵敏度取决于造影剂与“主体”水质子之间的质子转移交换率kex。为了利用较大的kex,交换性质子池之间需要较大的频率间隔(Δω)。因此,高磁场更受青睐。本文表明,使用具有大有效磁矩的基于镧系(III)离子的顺磁性CEST造影剂能够在1特斯拉(T)的相对低场强下进行CEST实验。

方法

在1T磁共振扫描仪上使用连续波(cw)预饱和和自旋回波序列进行测量。通过在室温及pH值为7的条件下将配体与Ln(III)Cl3按化学计量比混合来合成ParaCEST复合物。

结果

研究了不同的镧系螯合物(Tm-、Dy-、Yb-、Eu-HPDO3A和Eu-DOTAMGly)。已证明比例测量法(Tm-HPDO3A)和选择性检测法(Eu-DOTAMGly和Tm-HPDO3A)在体内是可行的。

结论

体外实验证明,除Eu-HPDO3A外,CEST方法在1T磁场下对几乎所有研究中的ParaCEST候选物都是可行的。在所研究的化合物中,Tm-HPDO3A被证明适用于在体外和体内评估pH值的比例测量法。

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