Oxidative Conversion of a Europium(II)-Based T1 Agent into a Europium(III)-Based paraCEST Agent that can be Detected In Vivo by Magnetic Resonance Imaging

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