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
Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes...Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.展开更多
In order to compare the potential selectivity of R-（-）-DM-phencynonate hydrochloride with its racemate （±）-DM- phencynonate hydrochloride on acetylcholine muscarinic receptor subtypes, the five human acetylch...In order to compare the potential selectivity of R-（-）-DM-phencynonate hydrochloride with its racemate （±）-DM- phencynonate hydrochloride on acetylcholine muscarinic receptor subtypes, the five human acetylcholine muscarinic receptor subtypes （M1- M5） （CHO-hml-5R） were cloned and expressed in Chinese hamster ovary （CHO-K1） cell line. The specific mRNAs of the five acetylcholine muscarinic receptor subtypes were detected by the reverse transcription-polymerase chain reaction （RT-PCR） method, demonstrating the definite expression of muscarinic receptor subtype genes （CHO-hml-5R）. The affinity and saturability of different muscarinic receptor subtypes to [^3H] N-methylscopolamine （[^3H]-NMS） were obtained by radioligand binding assay. Equilibrium binding assay revealed that the maximum binding capacity of [^3H]-NMS （Bmax value） to CHO-hml-5R were 40.22±3.23, 24.53±4.11, 29.65±2.65, 25.41±2.46, 32.78±4.81 pmol/mg·protein, respectively. Kd values of [^3H]-NMS to muscarinic receptors M1 to M5 were 0.97±0.22, 1.16±0.14, 0.99±0.06, 0.56±0.08, 1.12±0.06 nM, respectively. R-（-）-DM- phencynonate hydrochloride was found to block the M4 receptor with a much higher potency （pD2 = 7.48） than those displayed on M1 （pD2 = 6.20）, M2 （pD2 = 5.99）, M3 （pD2 = 5.99） and M5 （pD2 = 6.70） subtypes. However, for （±）-DM-phencynonate hydrochloride, no significant subtype receptor selectivity was found. Both （±）-DM- and R-（-）-DM-phencynonate hydrochloride showed allosteric effects on muscarinic receptors, the Hill coefficient （nH） of five receptor subtypes was less than 1, respectively. The results revealed that R-（-）-DM-phencynonate hydrochloride showed selectivity torwards M4 subtype, and there were allosteric effects for both R-（-）-DM-phencynonate hydrochloride and （±）-DM-phencynonate hydrochloride on muscarinic receptors.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Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.
基金National Natural Science Foundation of China (Grant No. 30672445)
文摘In order to compare the potential selectivity of R-（-）-DM-phencynonate hydrochloride with its racemate （±）-DM- phencynonate hydrochloride on acetylcholine muscarinic receptor subtypes, the five human acetylcholine muscarinic receptor subtypes （M1- M5） （CHO-hml-5R） were cloned and expressed in Chinese hamster ovary （CHO-K1） cell line. The specific mRNAs of the five acetylcholine muscarinic receptor subtypes were detected by the reverse transcription-polymerase chain reaction （RT-PCR） method, demonstrating the definite expression of muscarinic receptor subtype genes （CHO-hml-5R）. The affinity and saturability of different muscarinic receptor subtypes to [^3H] N-methylscopolamine （[^3H]-NMS） were obtained by radioligand binding assay. Equilibrium binding assay revealed that the maximum binding capacity of [^3H]-NMS （Bmax value） to CHO-hml-5R were 40.22±3.23, 24.53±4.11, 29.65±2.65, 25.41±2.46, 32.78±4.81 pmol/mg·protein, respectively. Kd values of [^3H]-NMS to muscarinic receptors M1 to M5 were 0.97±0.22, 1.16±0.14, 0.99±0.06, 0.56±0.08, 1.12±0.06 nM, respectively. R-（-）-DM- phencynonate hydrochloride was found to block the M4 receptor with a much higher potency （pD2 = 7.48） than those displayed on M1 （pD2 = 6.20）, M2 （pD2 = 5.99）, M3 （pD2 = 5.99） and M5 （pD2 = 6.70） subtypes. However, for （±）-DM-phencynonate hydrochloride, no significant subtype receptor selectivity was found. Both （±）-DM- and R-（-）-DM-phencynonate hydrochloride showed allosteric effects on muscarinic receptors, the Hill coefficient （nH） of five receptor subtypes was less than 1, respectively. The results revealed that R-（-）-DM-phencynonate hydrochloride showed selectivity torwards M4 subtype, and there were allosteric effects for both R-（-）-DM-phencynonate hydrochloride and （±）-DM-phencynonate hydrochloride on muscarinic receptors.
