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

作者：Nan Wu, Xiaojun Zhang, Yuying Li, Jinming Zhang, Mengchao Cui · 发表于：Journal of Medicinal Chemistry · 年份：2024 · DOI：10.1021/acs.jmedchem.4c01952 · 被引用次数：6 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neuroscience and Neuropharmacology Research、Adenosine and Purinergic Signaling

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, [ 18 F] 8, which demonstrated high affinity for MAO-B (IC 50 = 0.59 nM) and appreciable brain pharmacokinetics (SUV max = 2.15 at 2 min, brain 2min/60min = 7.67) in rats. Furthermore, the radioactivates from [ 18 F] 8 in regions of MAO-B expression could be effectively inhibited by Selegiline. All these positive findings supported that [ 18 F] 8 is a promising candidate for MAO-B PET imaging, which merits further evaluation.