PARACEST agents: Modulating MRI contrast via water proton exchange

Scientific interest in optimizing the properties of gadolinium (III) complexes as MRI contrast agents has led to many new insights into lanthanide ion coordination chemistry in the last two decades. Among these was the surprising observation that water exchange in lanthanide (III) derivatives of DOTA can be modulated dramatically by judicious choice of ligand side chain and Ln(3+) ionic radii. This resulted in the discovery of paramagnetic CEST agents for altering MRI image contrast based upon the chemical exchange saturation transfer mechanism. The goal of this article is to review the factors that govern water molecule and water proton exchange in these complexes and to compare the potential sensitivity of PARACEST agents versus Gd3+-based T-1 relaxation agents for altering tissue contrast.