Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging.

Monoamine oxidase-B (MAO-B), predominantly exists on the outer mitochondrial membrane of astrocytes, serves as a crucial biomarker for reactive astrocytes during neuroinflammatory responses and various neurodegenerative diseases. In this study, we synthesized a series of fluorinated coumarin derivatives and evaluated their structure-activity relationship and subtype selectivity for MAO-B. Following this, the preclinical bioevaluation containing positron emission tomography (PET) imaging and autoradiography studies led to the identification of the novel PET tracer, [F], which demonstrated high affinity for MAO-B (IC = 0.59 nM) and appreciable brain pharmacokinetics (SUV = 2.15 at 2 min, brain = 7.67) in rats. Furthermore, the radioactivates from [F] in regions of MAO-B expression could be effectively inhibited by Selegiline. All these positive findings supported that [F] is a promising candidate for MAO-B PET imaging, which merits further evaluation.