[18F]BIBD-181: A Novel Positron Emission Tomography Tracer Specific for Synaptic Vesicle Glycoprotein 2A

Dysfunction or decreased expression of synapticvesicle glycoprotein 2A (SV2A) is closely related to theprogression of neurodegenerative diseases and psychiatricdisorders. The development of positron emission tomography(PET) tracers targeting SV2A can provide a strong imaging basisfor the diagnosis and treatment of these diseases. Herein we reportthe synthesis of the novel radiotracer [18F]BIBD-181 and itspreclinical evaluation. The absolute configuration of BIBD-181 wasconfirmed by the single-crystal structure of its precursor. The invitro binding assay of BIBD-181 showed high SV2A bindingaffinity. Compared with previously reported tracers, [18F]BIBD-181 has mild labeling conditions, simple operation, and high yield.The in vivo metabolism of [18F]BIBD-181 is similar to that of UCB derivatives, and the metabolites do not interfere with brain PETimaging. Biodistribution and PET studies showed that [18F]BIBD-181 has high brain uptake and good pharmacokinetics.Autoradiography and PET inhibition studies indicated that [18F]BIBD-181 specifically binds SV2A. Because [18F]BIBD-181 exhibitsexcellent properties, it may be a reliable probe of quantities for SV2A-related disease diagnosis.