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Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme's aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [ 18 F] 10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [ 18 F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.

Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging

Development of [¹⁸F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging