Abstract
The chemistry of Gd(3+)-based MRI agents has advanced considerably during the past decade toward agents with higher relaxivity and agents that respond to physiology and/or metabolism. This review describes various approaches that have been taken toward the development of responsive contrast agents and discusses the importance of fast water exchange for advancement of targeted Gd(3+)-based agents with higher sensitivity. The recent discovery of Eu(3+) complexes having extraordinarily slow water exchange has opened a new avenue in contrast agent design based upon the chemical exchange saturation transfer (CEST) mechanism. These new paramagnetic complexes called PARACEST agents offer new possibilities of imaging biological functions such as tissue pH and metabolite levels. The lower detection limits that may apply to each class of contrast agent (Gd(3+)-based versus PARACEST) are discussed and the extent to which they may be applied to the imaging of β-cells is considered.