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

Autor: Yoshimoto M; Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.; Division of Functional Imaging, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan., Hirata M; Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan., Kagawa S; Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.; Division of PET Imaging, Shiga Medical Center Research Institute, Moriyama, Japan., Magata Y; Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Department of Molecular Imaging, Institute for Medical Photonics Research, Preeminent Medial Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan., Ohmomo Y; Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan., Temma T; Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Jazyk: angličtina
Zdroj: Journal of labelled compounds & radiopharmaceuticals [J Labelled Comp Radiopharm] 2019 Jul; Vol. 62 (9), pp. 580-587.
DOI: 10.1002/jlcr.3779
Abstrakt: 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.
(© 2019 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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