Lanthanide-Based T 2ex and CEST Complexes Provide Insights into the Design of pH Sensitive MRI Agents

Angew Chem Int Ed Engl. 2017 Dec 22;56(52):16626-16630. doi: 10.1002/anie.201707959. Epub 2017 Dec 4.


The CEST and T1 /T2 relaxation properties of a series of Eu3+ and Dy3+ DOTA-tetraamide complexes with four appended primary amine groups are measured as a function of pH. The CEST signals in the Eu3+ complexes show a strong CEST signal after the pH was reduced from 8 to 5. The opposite trend was observed for the Dy3+ complexes where the r2ex of bulk water protons increased dramatically from ca. 1.5 mm-1 s-1 to 13 mm-1 s-1 between pH 5 and 9 while r1 remained unchanged. A fit of the CEST data (Eu3+ complexes) to Bloch theory and the T2ex data (Dy3+ complexes) to Swift-Connick theory provided the proton-exchange rates as a function of pH. These data showed that the four amine groups contribute significantly to proton-catalyzed exchange of the Ln3+ -bound water protons even though their pKa 's are much higher than the observed CEST or T2ex effects. This demonstrated the utility of using appended acidic/basic groups to catalyze prototropic exchange for imaging tissue pH by MRI.

Keywords: MRI contrast agents; amide ligands; chemical exchange saturation transfer (CEST); lanthanide complexes; pH responsive.

Publication types

  • Research Support, Non-U.S. Gov't