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Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography(PET)

Acta Pharmaceutica Sinica B 2019年第6期9卷 1204-1215页

作者： Yu Lan Ping Bai Zude Chen Ramesh Neelamegam Michael SPlaczek Hao Wang Stephanie AFiedler Jing Yang Gengyang Yuan Xiying Qu hayden rschmidt Jinchun Song Marc DNormandin Chongzhao Ran Changning Wang Athinoula A.Martinos Center for Biomedical Imaging Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA Gordon Center for Medical Imaging Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA Department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02129USA Department of Pharmacy Renmin Hospital of Wuhan UniversityWuhan 430060China

The sigma-1 receptor(σ1R)is a unique intracellular protein.σ1R plays a major role in various pathological conditions in the central nervous system(CNS),implicated in several neuropsychiatric *** ofσ1R in the brain using positron emission tomography(PET)could serve as a noninvasively tool for enhancing the understanding of the disease’s ***,σ1R PET tracers can be used for target validation and quantification in ***,we describe the radiosynthesis,in vivo PET/CT imaging of novelσ1R11C-labeled radioligands based on 6-hydroxypyridazinone,[11C]HCC0923 and[11C]*** radioligands have high affinities toσ1R,with good *** mice PET/CT imaging,both radioligands showed appropriate kinetics and ***,the specific interactions of two radioligands were reduced by compounds 13 and 15(self-blocking).Ofthe two,[11C]HCC0929 was further investigated in positive ligands blocking studies,using classicσ1R agonist SA 4503 andσ1R antagonist PD ***σ1R ligands could extensively decreased the uptake of[11C]HCC0929 in mice ***,the biodistribution of major brain regions and organs of mice were determined in *** studies demonstrated that two radioligands,especially[11C]HCC0929,possessed ideal imaging properties and might be valuable tools for non-invasive quantification ofσ1R in brain.

关键词： σ1R PET Brain imaging 6-Hydroxypyridazinone 11C-labeled radioligand

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