[18F]ASEM([18F]ASEM) - 药物靶点：CHRNA7_在研适应症：精神分裂症，烟草依赖，精神障碍_专利_临床

概要

基本信息

药物类型

小分子化药、诊断用放射药物

别名

[18F]JHU-82132

靶点

CHRNA7

作用机制

α7 receptor拮抗剂(神经性乙酰胆碱受体蛋白α-7亚基拮抗剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

神经系统疾病其他疾病

在研适应症

精神分裂症烟草依赖精神障碍

非在研适应症-

原研机构

Georgetown University in Qatar

在研机构

Georgetown University in Qatar

Washington University School of Medicine

The Johns Hopkins University School of Medicine

+ [1]

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C19H19FN2O2S

InChIKeyJIGWWGDIEUWCOR-LRFGSCOBSA-N

CAS号1456878-52-6

关联

2

项与 [18F]ASEM 相关的临床试验

NCT05462340

/ Recruiting临床1期IIT

PET Imaging Study of α7 and α4β2-nAChR in Schizophrenia: Cognitive Relationships

The purpose of this research is to use specialized brain imaging techniques, Positron Emission Tomography (PET) scan and Magnetic Resonance Imaging (MRI), to learn more about the brain chemistry, e.g., how neurotransmitters and receptors in the brain function in people with schizophrenia compared to healthy controls.

开始日期2022-08-18

申办/合作机构

Washington University School of Medicine

NCT04055467

/ Completed临床1期IIT

Brain Imaging of Nicotinic Acetylcholine Receptors in Tobacco Users and Nonusers

The proposed study will help fill gaps in existing research by determining if nicotine-dependent cigarette smokers show changes in α7 nicotinic acetylcholine receptor (nAChR) availability when compared to matched historical controls using positron emission tomography (PET) imaging and the radioactive ligand [18F]-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6 [18F]fluorodibenzo[b,d]thiophene 5,5-dioxide), an α7 nAChR antagonist. The study will also explore whether α7 nAChR availability influences clinically relevant measures of tobacco abstinence (e.g., withdrawal and craving, cognitive impairment), self-reported cigarettes per day, and time to relapse during an 8-day quit attempt during which smokers can receive escalating payments contingent upon providing objective evidence (breath CO and urinary cotinine) of smoking abstinence.

开始日期2019-12-16

申办/合作机构

The Johns Hopkins University

[+1]

100 项与 [18F]ASEM 相关的临床结果

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100 项与 [18F]ASEM 相关的转化医学

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100 项与 [18F]ASEM 相关的专利（医药）

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2

项与 [18F]ASEM 相关的文献（医药）

2017-06-01·European Journal of Nuclear Medicine and Molecular Imaging

PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans

Article

作者: Zheng, Ming-Qiang ; Hillmer, Ansel T ; Huang, Yiyun ; Cosgrove, Kelly P ; Deuther-Conrad, Winnie ; Ropchan, Jim ; Teodoro, Rodrigo ; Pracitto, Richard ; Carson, Richard E ; Holden, Daniel ; Brust, Peter ; Esterlis, Irina ; Li, Songye ; Lin, Shu-Fei ; Nabulsi, Nabeel ; Scheunemann, Matthias ; Labaree, David

PURPOSE:

The α₇ nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α₇ nAChRs PET radioligands, [¹⁸F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [¹⁸F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [¹⁸F]ASEM in humans.

METHODS:

PET scans with high specific activity [¹⁸F]ASEM or [¹⁸F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [¹⁸F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [¹⁸F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [¹⁸F]ASEM distribution volume (V _T). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V _T was assessed.

RESULTS:

In the rhesus monkey brain [¹⁸F]ASEM and [¹⁸F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [¹⁸F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [¹⁸F]ASEM V _T. [¹⁸F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [¹⁸F]ASEM V _T in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V _T values ranging from 19.6 ± 2.5 mL/cm³ in cerebellum to 25.9 ± 2.9 mL/cm³ in thalamus. Test-retest variability of V _T was 11.7 ± 9.8%.

CONCLUSIONS:

These results confirm [¹⁸F]ASEM as a suitable radiotracer for the imaging and quantification of α₇ nAChRs in humans.

2015-04-01·Journal of labelled compounds & radiopharmaceuticals4区 · 医学

Microwave-assisted radiosynthesis of [¹⁸F]ASEM, a radiolabeledα7-nicotinic acetylcholine receptor antagonist

4区 · 医学

Article

作者: Gao, Yongjun ; Holt, Daniel P. ; Dannals, Robert F. ; Ravert, Hayden T. ; Horti, Andrew G.

An improvement of the original radiochemical synthesis of [(18) F]ASEM, an α7-nicotinic acetylcholinergic receptor radioligand, is reported. The new procedure utilizes microwave-assisted radiofluorination. In addition, a new preparative HPLC method was developed to eliminate a chemical impurity in the final product. Quality control procedures were also enhanced to improve detection of product with enhanced resolution of potential impurities. [(18) F]ASEM was produced in 20.1 ± 8.9% non-decay corrected (NDC) yield with an average synthesis time of 57 min and an average specific radioactivity of 856 ± 332 GBq/µmol (23 ± 9 Ci/µmol).

100 项与 [18F]ASEM 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
精神分裂症	临床1期	美国	Washington University School of Medicine	2022-08-18
烟草依赖	临床1期	美国	National Institute on Drug Abuse	2019-12-16
精神障碍	临床1期	-	Georgetown University in Qatar	-
精神障碍	临床1期	-	The Johns Hopkins University School of Medicine	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04055467 (CTgov)	临床1期	烟草依赖	15	Contingency Management+[F18]-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[18F]fluorodibenzo[b,d]thiophene 5,5-dioxide)	衊範範衊蓋構遞獵構餘(選範積鑰範糧顧願築膚) = 糧網鬱襯廠鹽醖網廠淵積繭鏇積選壓壓繭膚淵 (繭鹽窪糧壓獵醖願構廠, 遞廠觸鏇繭積窪選選鏇 ~ 獵齋遞遞夢餘顧糧衊膚) 更多	-	2024-08-06
SNMMI2017	N/A	-	-	18F-ASEM (Test-retest group)	窪夢襯窪鬱顧遞繭淵糧(顧壓蓋鏇鬱壓淵構簾淵) = 獵遞齋艱艱鹹繭遞糧糧鏇鏇糧襯積簾淵構夢醖 (鹽糧範獵齋鏇衊糧獵遞 )	-	2017-05-24
SNMMI2017	N/A	-	-	DXMB-A pre-treated group	糧構築範鬱蓋網鹹觸壓(淵鹽網顧觸網窪醖衊簾) = 蓋積蓋簾餘鏇築範壓簾窪簾鑰鹽鹽願壓構鬱夢 (觸糧壓簾膚獵鹽憲構構 )	-	2017-05-24