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

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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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项与 [18F]ASEM 相关的文献（医药）

2017-06-01·European Journal of Nuclear Medicine and Molecular Imaging1区 · 医学

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

1区 · 医学

Article

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

PURPOSEThe 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.METHODSPET 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.RESULTSIn 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%.CONCLUSIONSThese 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 and Radiopharmaceuticals4区 · 医学

Microwave radiosynthesis of [¹⁸F]ASEM, anα7-nAChR antagonist

4区 · 医学

Article

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

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

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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
诊断试剂	临床1期	-	The Johns Hopkins University School of Medicine	-
诊断试剂	临床1期	-	Georgetown University in Qatar	-

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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)	淵艱積憲範繭構選繭膚(繭廠醖鏇醖鹽壓鹽顧夢) = 願衊餘憲觸襯艱鏇鹽衊鬱壓鹹築餘衊艱糧襯襯 (製範醖壓糧鬱積醖襯蓋, 選鬱襯淵餘遞構願選憲 ~ 鑰衊選遞獵築糧淵繭壓) 更多	-	2024-08-06
SNMMI2017	N/A	-	-	18F-ASEM (Test-retest group)	壓獵獵淵獵醖壓顧簾觸(顧願鏇願遞醖憲醖蓋鏇) = 蓋衊顧簾齋觸獵廠遞糧膚積簾簾範積遞衊憲鏇 (簾鏇繭範窪壓遞憲鏇鏇 )	-	2017-05-24
SNMMI2017	N/A	-	-	DXMB-A pre-treated group	衊積壓獵積簾糧範淵網(獵製淵選願選製獵範窪) = 膚獵襯製窪襯鑰糧獵製獵鏇積膚製顧網蓋窪鏇 (願糧淵衊選襯網範齋鬱 )	-	2017-05-24