Nicotinic acetylcholine receptors(nChRs) are involved in the various pharmacological effects or disease states.In order to study the central nChRs by PET or SPECT,some radioligands have been investigated.In this paper...Nicotinic acetylcholine receptors(nChRs) are involved in the various pharmacological effects or disease states.In order to study the central nChRs by PET or SPECT,some radioligands have been investigated.In this paper,the procedure for synthesis of 2-[^18F] fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine(2-[^18F0-A-85380),a potential PET ligand for in vivo imaging nicotinic acetylcholine receptor was described.2-[^18F]-A-85380 was prepared from the precursor,2-nitro-3-[(1-(tert-butoxycarbonyl)-2-(S0-azetidinyl)methoxy] pyridine(4),which was synthesized with commercial (S)-2-zaetid-inecarboxylic acid as starting material.The whole procedure for radiosynthesis and purification was executed in about 1h and 45-55% of the added fluorine-18 was found in the purified 2-[^18F]-A-85380,with specific activity of 1.0-2.2×10^11 Bq/umol.展开更多
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
Objective To investigate the expression and the binding characteristics of leptin receptor (Ob-R) on human osteoblast. Methods The human osteoblasts were cultured and identified by cell biological criteria. 125I-lepti...Objective To investigate the expression and the binding characteristics of leptin receptor (Ob-R) on human osteoblast. Methods The human osteoblasts were cultured and identified by cell biological criteria. 125I-leptin was prepared by chloramine-T method and purified by PAGE. Radioligand binding assay of receptor and Scatchard plot were performed to identify the binding properties of the osteoblasts. Results Morphologically, the cultured cells showed analogical phenotype to osteoblast, and were positive in histochemical and immuno-fluorence staining for alkaline phosphatase and osteocalcin, respectively. The Alizarin Reds staining showed that mineralization was also developed by supplementation with ascorbate and β-glycerophosphate. The percentages of 125I-leptin binding to osteoblast were 16.7%±2.3% and 6.1%±1.4% without and with unlabelled leptin, respectively. From the saturation assay and by Scatchard plotting, a single class of high-affinity binding sites of Ob-R for leptin was identified with an apparent kd of 0.11±0.06 nmol/L and a Bmax of 1.7±0 3 nmol/10 5 cells. Conclusion The human osteoblasts are target of leptin, with expression of Ob-R. The leptin could possibly regulate the growth, prolifiration, function of osteoblasts and even bone remoldeling.展开更多
文摘Nicotinic acetylcholine receptors(nChRs) are involved in the various pharmacological effects or disease states.In order to study the central nChRs by PET or SPECT,some radioligands have been investigated.In this paper,the procedure for synthesis of 2-[^18F] fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine(2-[^18F0-A-85380),a potential PET ligand for in vivo imaging nicotinic acetylcholine receptor was described.2-[^18F]-A-85380 was prepared from the precursor,2-nitro-3-[(1-(tert-butoxycarbonyl)-2-(S0-azetidinyl)methoxy] pyridine(4),which was synthesized with commercial (S)-2-zaetid-inecarboxylic acid as starting material.The whole procedure for radiosynthesis and purification was executed in about 1h and 45-55% of the added fluorine-18 was found in the purified 2-[^18F]-A-85380,with specific activity of 1.0-2.2×10^11 Bq/umol.
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.
文摘Objective To investigate the expression and the binding characteristics of leptin receptor (Ob-R) on human osteoblast. Methods The human osteoblasts were cultured and identified by cell biological criteria. 125I-leptin was prepared by chloramine-T method and purified by PAGE. Radioligand binding assay of receptor and Scatchard plot were performed to identify the binding properties of the osteoblasts. Results Morphologically, the cultured cells showed analogical phenotype to osteoblast, and were positive in histochemical and immuno-fluorence staining for alkaline phosphatase and osteocalcin, respectively. The Alizarin Reds staining showed that mineralization was also developed by supplementation with ascorbate and β-glycerophosphate. The percentages of 125I-leptin binding to osteoblast were 16.7%±2.3% and 6.1%±1.4% without and with unlabelled leptin, respectively. From the saturation assay and by Scatchard plotting, a single class of high-affinity binding sites of Ob-R for leptin was identified with an apparent kd of 0.11±0.06 nmol/L and a Bmax of 1.7±0 3 nmol/10 5 cells. Conclusion The human osteoblasts are target of leptin, with expression of Ob-R. The leptin could possibly regulate the growth, prolifiration, function of osteoblasts and even bone remoldeling.
