A series of N-methyl-D-aspartate (NMDA) receptor-targeted MRI contrast agents has been developed, based on the known competitive NMDA antagonist, 3,4-diamino-3-cyclobutene-1,2-dione. Their use as responsive MR imaging probes has been evaluated in vitro and two contrast agents showed 170–176% enhancements in relaxation rate, following incubation with a neuronal cell line model. A derivative of the lead compound was prepared containing a biotin moiety, and both the specificity and reversibility of binding to the NMDA cell surface receptors demonstrated using confocal microscopy.
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