Deprotonation of the phenolic proton of Eu-pH sensor complex results in more negative charge placed on the carbonyl oxygen atom to coordinate with the Eu3+ ion (above) and a downfield shift in the exchanging Eu3+-bound water CEST peak from 50 to 55 ppm (below). [Eu3+] = 10 mM, B1 = 14.1 µT, and sat. time = 2 s.
Polymeric PARACEST agents for enhancing MRI contrast sensitivity. PARACEST agents are a new class of MRI contrast agents that offer a number of advantages over conventional Gd3+ agents, but one of the major limitations of current small-molecule CEST agents is their relatively low contrast sensitivity. My first research is the synthesis and use of polymeric PARACEST systems with large numbers of exchangeable groups to improve contrast sensitivity. The polymeric agents showed a much lower detection limit in the range of 60–130 uM compared 1300–1700 uM for the monomer.
Ratiometric PARACEST agents that are responsive to pH. Given that image contrast produced by PARACEST agents is extremely sensitive to chemical exchange rates (kex), sensors for detection of a variety of biological species have been developed. However, quantitative CEST pH sensing has only been achieved by using a cocktail of agents having weakly shifted –NH protons for ratiometric imaging, wherein one proton exchange pool is used as the CEST sensor for pH and another pool as a concentration marker. My second research is the development of PARACEST agent with an exchanging Eu3+-bound water resonance that shifts (50-55 ppm) with pH changes. This feature allows a direct measure of pH in a single experiment by ratiometric imaging.
|Polymeric PARACEST agents||Responsive MRI agents|
|Targeted dual-modality MRI/PET contrast agents|