Investigations into whole water, prototropic and amide proton exchange in lanthanide(III) DOTA-tetraamide chelates.

Lanthanide(III) chelates of DOTA-tetraamide ligands have been an area of particular interest since the discovery that water exchange kinetics are dramatically affected by the switch from acetate to amide side-chain donors. More recently these chelates have attracted interest as potential PARACEST agents for use in MRI. In this paper we report the results of studies using chemical exchange saturation transfer (CEST) and some more recently reported chelates to re-examine the exchange processes in this class of chelate. We find that the conclusions of Parker and Aime are, for the most part, solid; water exchange is slow and a substantial amount of prototropic exchange occurs in aqueous solution. The extent of prototropic exchange increases as the pH increases above 8, leading to higher relaxivities at high pH. However, amide protons are found to contribute only a small amount to the relaxivity at high pH.