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 in vivo positron emission tomography (PET) imaging and ex vivo autoradiography studies led to the identification of the novel PET tracer, [18F]8, which demonstrated high affinity for MAO-B (IC50 = 0.59 nM) and appreciable brain pharmacokinetics (SUVmax = 2.15 at 2 min, brain2min/60min = 7.67) in rats. Furthermore, the radioactivates from [18F]8 in regions of MAO-B expression could be effectively inhibited by Selegiline. All these positive findings supported that [18F]8 is a promising candidate for MAO-B PET imaging, which merits further evaluation.

https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01952