Lanthanide-based T2ex and CEST complexes provide new insights into the design of pH sensitive MRI agents

Angewandte Chemie - International Edition

4 years ago

Lanthanide-based T2ex and CEST complexes provide new insights into the design of pH sensitive MRI agents

Dean Sherry, Yunkou Wu, Gyula Tircso, Lei Zhang, Andre F. Martins, Piyu Zhao

A series of Eu3+ and Dy3+ DOTA-tetraamide complexes with four appended primary amine groups were prepared and their CEST and T1/T2 relaxation properties measured as a function of pH. The CEST signals in the Eu3+ complexes show a surprisingly 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 ~1.5 mM-1s-1 to ~13 mM-1s-1, while r1 remained unchanged. A fit of the CEST data (Eu3+ complexes) to Bloch theory and the T2 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201707959