Oxidative Conversion of a Europium(II)-BasedT1Agent into a Europium(III)-Based paraCEST Agent that can be Detected In Vivo by Magnetic Resonance Imaging

The EuII complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most EuII chelates reported to date. The reduced EuII form acts as an efficient water proton T1 relaxation reagent, while the EuIII form acts as a water-based chemical exchange saturation transfer (CEST) agent. The complex has extremely fast water exchange rate. Oxidation to the corresponding EuIII complex yields a well-defined signal from the paraCEST agent. The time course of oxidation was studied in vitro and in vivo by T1-weighted and CEST imaging.