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

Magn Reson Med. 2002 Apr;47(4):639-48. doi: 10.1002/mrm.10106.


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 displays 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry
  • Contrast Media* / chemistry
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Lanthanoid Series Elements*
  • Ligands
  • Magnetic Resonance Imaging
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*


  • Chelating Agents
  • Contrast Media
  • Heterocyclic Compounds, 1-Ring
  • Lanthanoid Series Elements
  • Ligands
  • Organometallic Compounds
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Glycine