1.Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET).
Yu LAN ; Ping BAI ; Zude CHEN ; Ramesh NEELAMEGAM ; Michael S PLACZEK ; Hao WANG ; Stephanie A FIEDLER ; Jing YANG ; Gengyang YUAN ; Xiying QU ; Hayden R SCHMIDT ; Jinchun SONG ; Marc D NORMANDIN ; Chongzhao RAN ; Changning WANG
Acta Pharmaceutica Sinica B 2019;9(6):1204-1215
The sigma-1 receptor (R) is a unique intracellular protein. R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, PET/CT imaging of novel R C-labeled radioligands based on 6-hydroxypyridazinone, [C]HCC0923 and [C]HCC0929. Two radioligands have high affinities to R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds and (self-blocking). Of the two, [C]HCC0929 was further investigated in positive ligands blocking studies, using classic R agonist SA 4503 and R antagonist PD 144418. Both R ligands could extensively decreased the uptake of [C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined . These studies demonstrated that two radioligands, especially [C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of R in brain.
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