A paramagnetic CEST agent for imaging glucose by MRI

The europium(III) complex of a DOTA?tetraamide ligand (DOTA = 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acids) containing two phenyl boronate pendent arms binds glucose reversibly with an association constant of 383 M-1 at pH 7. Glucose binding results in slowing of water exchange between a single Eu(III)-bound water molecule and bulk water, and this can be imaged by MRI using chemical exchange saturation transfer (CEST) imaging sequence. This metabolite-responsive paramagnetic CEST agent responds to changes in glucose over the physiologically important range (0?20 mM), and thus it offers the possibility of high-sensitivity MR imaging glucose in tissues using bulk water protons as antenna. Copyright © 2003 American Chemical Society.