Solution-state CEST MRI of two PARACEST agents. a) The horizontal reaction shows MR saturation of the amide proton of ZGGR-α-amino-(Tm-DOTA) (gray), followed by chemical exchange with water, which transfers the MR saturation to water and decreases the water signal. The vertical reaction shows cleavage of the ZGGR peptide from α-amino-(Tm-DOTA) by uPA, which converts an amide to an amine that does not generate CEST. b) ZGGR-α-amino-(Tm-DOTA) showed CEST with MR saturation at −54.1 ppm before adding uPA (black) but not after adding uPA (gray). A control agent, Eu-DOTA-Gly4, showed no change in CEST at +53.9 ppm.