Dysfunction or decreased expression of synaptic vesicle glycoprotein 2A (SV2A) is closely related to the progression of neurodegenerative diseases and psychiatric disorders. The development of positron emission tomography (PET) tracers targeting SV2A can provide a strong imaging basis for the diagnosis and treatment of these diseases. Herein we report the synthesis of the novel radiotracer [18F]BIBD-181 and its preclinical evaluation. The absolute configuration of BIBD-181 was confirmed by the single-crystal structure of its precursor. The in vitro binding assay of BIBD-181 showed high SV2A binding affinity. 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 PET imaging. 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 exhibits excellent properties, it may be a reliable probe of quantities for SV2A-related disease diagnosis.
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