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 disorders.Imaging ofσ1R...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 disorders.Imaging ofσ1R in the brain using positron emission tomography(PET)could serve as a noninvasively tool for enhancing the understanding of the disease’s pathophysiology.Moreover,σ1R PET tracers can be used for target validation and quantification in diagnosis.Herein,we describe the radiosynthesis,in vivo PET/CT imaging of novelσ1R11C-labeled radioligands based on 6-hydroxypyridazinone,[11C]HCC0923 and[11C]HCC0929.Two radioligands have high affinities toσ1R,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 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 144418.Bothσ1R ligands could extensively decreased the uptake of[11C]HCC0929 in mice brain.Besides,the biodistribution of major brain regions and organs of mice were determined in vivo.These studies demonstrated that two radioligands,especially[11C]HCC0929,possessed ideal imaging properties and might be valuable tools for non-invasive quantification ofσ1R in brain.展开更多
基金supported by a pilot funding from the Athinoula A.Martinos Center for Biomedical Imaging at the Massachusetts General Hospital(Changning Wang,USA)National Natural Science Foundation of China(Grant No.81602946,Yu Lan)Natural Science Foundation of Hubei Province of China(Grant No.2016CFB258,Yu Lan).
文摘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 disorders.Imaging ofσ1R in the brain using positron emission tomography(PET)could serve as a noninvasively tool for enhancing the understanding of the disease’s pathophysiology.Moreover,σ1R PET tracers can be used for target validation and quantification in diagnosis.Herein,we describe the radiosynthesis,in vivo PET/CT imaging of novelσ1R11C-labeled radioligands based on 6-hydroxypyridazinone,[11C]HCC0923 and[11C]HCC0929.Two radioligands have high affinities toσ1R,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 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 144418.Bothσ1R ligands could extensively decreased the uptake of[11C]HCC0929 in mice brain.Besides,the biodistribution of major brain regions and organs of mice were determined in vivo.These studies demonstrated that two radioligands,especially[11C]HCC0929,possessed ideal imaging properties and might be valuable tools for non-invasive quantification ofσ1R in brain.
