Selective sensing of zinc ions with a PARACEST contrast agent.
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Biomedical subjects
Publications and source records attributed to Robert Trokowski.
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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.
Novel cyclen-based phenylboronate ligands and their corresponding Eu(3+) complexes have been examined as glucose sensors using chemical exchange saturation transfer (CEST) MR imaging for detection. Two isomeric bis-phenylboronate complexes, Eu(4) and Eu(10), and a mono-phenylboronate complex, Eu(12), had been prepared and characterized by UV and circular dichroism spectroscopy, mass spectrometry, and CEST imaging. Both the free ligands and their Eu(3+) complexes bind to simple sugars, but their selectivity and binding affinities vary with sugar structure. Interestingly, the free ligands, 4 and 10, are selective for fructose over glucose, but this selectivity order switches in the respective Eu(3+) complexes. Of the complexes examined, Eu(4) shows the highest selectivity and binding affinity for glucose (2275 +/- 266 M(-)(1) at pH 10.2 and 339 +/- 29 M(-)(1) at pH 7). Glucose acts as a "capping"moiety in the Eu(4).glucose binary complex and modulates water exchange between a single Eu(3+)-bound water molecule and bulk water, an effect that can be detected by CEST imaging. Thus, Eu(4) represents a new class of metabolite-specific imaging agents that may allow mapping of metabolites by MRI of the bulk water signal.