ABSTRACT

Paramagnetic chemical exchange saturation transfer (paraCEST)

MRI contrast agents typically consist of a paramagnetic metal ion

and an organic chelate to form a metal chelator. ParaCEST agents

have typically used a macrocyclic tetraazacyclododecane as the base

structure due to the high kinetic stabilities of these metal chelates.

The ligands of the metal chelates can include amide, amine, or

hydroxyl groups that slowly exchange protons with bulk water. In

addition, awatermoleculemay be tightly bound to themetal chelate,

causing the chemical exchange of the water molecule with bulk

solvent to be slow. Thus, this bound water molecule is considered

a part of the structure of the paraCEST agent. Selective radio

frequency (RF) saturation of a slowly exchanging proton in a ligand

or tightly bound water, followed by exchange with bulk water, can

generate the CEST signal.