The importance of water exchange rates in the design of responsive agents for MRI.

The rate of water exchange in lanthanide complexes is often overlooked as an important parameter in the design of responsive MR imaging agents. Most often, the number of inner-sphere water coordination sites or the rotational mobility of the complex is considered as the central theme while water exchange is either assumed to be "fast enough" or entirely ignored. On the contrary, relaxation and shift theories predict that water exchange rates may indeed be the key parameter one should consider in any new molecular design. In this short review, the impact of water exchange rates on three classes of lanthanide-based MRI contrast agents, T₁-based relaxation agents, T₂ exchange line-broadening agents and chemical exchange saturation transfer (CEST) agents, is illustrated and discussed.