Synthesis and characterization of novel radiofluorinated probes for positron emission tomography imaging of monoamine oxidase B

Monoamine oxidase B (MAO‐B), predominantly expressed in glial cells, plays an important role in neurotransmitter regulation, and MAO‐B activity relates to several neuronal diseases. Here, we aimed to develop a radiofluorinated MAO‐B imaging probe based on the structure of a selective MAO‐B inhibitor, MD‐230254. We synthesized and evaluated a series of compounds in vitro and in vivo. A series of fluorinated analogs of MD‐230254 were synthesized and evaluated for inhibitory potency and selectivity toward MAO‐B. 5‐[4‐(2‐[18F]Fluorobenzyloxy)phenyl]‐3‐(2‐cyanoethyl)‐1,3,4‐oxadiazol‐2(3H)‐one (2‐[18F]FBPO) was synthesized from a corresponding tributylstannyl precursor and [18F]CH3COOF. Biodistribution after intravenous injection of 2‐[18F]FBPO was evaluated in male ddY mice with or without pretreatment by inhibitors. Among the compounds synthesized and evaluated, 2‐FBPO showed high inhibitory potency and selectivity toward MAO‐B comparable with MD‐230254. 2‐[18F]FBPO was successfully synthesized by an electrophilic reaction with a high radiochemical purity of more than 99%. 2‐[18F]FBPO was efficiently taken up by the brain and showed rapid blood clearance, which provided a brain/blood radioactivity ratio of 3.7 at 90 minutes postinjection. The brain radioactivity was significantly decreased by pretreatment with an MAO‐B selective inhibitor. The great potential of 2‐[18F]FBPO as an MAO‐B imaging probe, applicable to a variety of diseases, is indicated. For the development of a radiofluorinated probe for monoamine oxidase B imaging by PET, 2‐[18F]FBPO was designed, synthesized, and evaluated in male ddY mice with or without treatment of inhibitors.