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

The CEST and T /T relaxation properties of a series of Eu and Dy DOTA-tetraamide complexes with four appended primary amine groups are measured as a function of pH. The CEST signals in the Eu complexes show a strong CEST signal after the pH was reduced from 8 to 5. The opposite trend was observed for the Dy complexes where the r of bulk water protons increased dramatically from ca. 1.5 mm  s to 13 mm  s between pH 5 and 9 while r remained unchanged. A fit of the CEST data (Eu complexes) to Bloch theory and the T data (Dy 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 Ln -bound water protons even though their pK 's are much higher than the observed CEST or T effects. This demonstrated the utility of using appended acidic/basic groups to catalyze prototropic exchange for imaging tissue pH by MRI.