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

Abstract

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-[ 18 F]Fluorobenzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one (2-[ 18 F]FBPO) was synthesized from a corresponding tributylstannyl precursor and [ 18 F]CH 3 COOF. Biodistribution after intravenous injection of 2-[ 18 F]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-[ 18 F]FBPO was successfully synthesized by an electrophilic reaction with a high radiochemical purity of more than 99%. 2-[ 18 F]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-[ 18 F]FBPO as an MAO-B imaging probe, applicable to a variety of diseases, is indicated. KEYWORDS MAO, MAO-B, MD-230254, monoamine oxidase, positron emission tomography, PET, SPECT Mitsuyoshi Yoshimoto and Masahiko Hirata contributed equally to this manuscript.

Role of Monoamine Oxidase Activity in Alzheimer’s Disease: An Insight into the Therapeutic Potential of Inhibitors

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Imaging of Reactive Astrogliosis by Positron Emission Tomography

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