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DOTAM-type ligands possessing arginine pendant groups for use in PARACEST MRI


R. H. E. Hudson, Department of Chemistry, The University of Western Ontario, London, ON, Canada N6A 5B7. Email:


A synthetic methodology was developed for the preparation of metal-chelating ligands that possess arginine pendant groups relying on the alkylation of 1,4,7,10-tetraazacyclododecane (cyclen) with arginine-containing electrophiles. Conditions for the selective trialkylation or peralkylation of cyclen are described, the outcome being dependent on the nature of the arginine-derived electrophile and the solvent used for the reaction. Lanthanide metal complexes of the ligands prepared by the described route were evaluated for their suitability as PARACEST contrast agents for use in magnetic resonance imaging. The Dy3+ and Tm3+ complexes display CEST effects that are associated with the amide protons proximate to the metal center. These signals exhibit pH dependence in the range of 6.0–8.0 and thus may have the potential for pH measurement in physiological range. Copyright © 2012 John Wiley & Sons, Ltd.

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