Background:
The brain enzyme phosphodiesterase-4D (PDE4D) may affect thinking and depression. Drugs with some radioactivity can attach to enzymes and be seen on a scan. Researchers want to test a new radioactive drug, 11C-T-1650, to measure PDE4D in the brain and body. They also want to see if the new drug BPN14770 blocks 11C-T-1650 from the brain. They want to learn more about psychiatric disorders and possible treatments.
Objectives:
To study how well 11C-T-1650 helps show PDE4D on a scan and to see if BPN14770 blocks it.
Eligibility:
Healthy adults at least 18 years old
Design:
Participants will be screened in other protocols.
Some participants will have 1 body PET scan.
Some participants will have 2 brain PET scans and 1 brain MRI within 1 year.
Some participants (ages 18 55) will:
Have 3 brain PET scans and 1 MRI
Take BPN14770 by mouth twice daily for 3 7 days
Have blood and urine tests
Have a follow-up physical exam and heart test
PET (positron emission tomography) scans will take 2 3 hours. Participants will:
Have a thin plastic tube (catheter) placed in an arm vein by needle.
Get a small amount of 11C-T-1650 injected via catheter. Another catheter may be placed to draw blood.
Lie quietly on a bed that slides into a donut-shaped scanner without sleeping. They may get a short break.
Have heart and vital signs monitored.
Have blood and urine tests.
Learn about drinking fluids and urinating after the scan
MRI (magnetic resonance imagining) scans will take 30 60 minutes:
Participants will lie on a table that slides into a metal cylinder in a magnetic field.
Sponsoring Institute: National Institute of Mental Health
...

开始日期2019-03-12

申办/合作机构

National Institute of Mental Health

100 项与 11C-T-1650 相关的临床结果

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100 项与 11C-T-1650 相关的转化医学

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100 项与 11C-T-1650 相关的专利（医药）

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项与 11C-T-1650 相关的文献（医药）

2020-05-06·ACS chemical neuroscience3区 · 医学

Discovery, Radiolabeling, and Evaluation of Subtype-Selective Inhibitors for Positron Emission Tomography Imaging of Brain Phosphodiesterase-4D

3区 · 医学

Article

作者: Pike, Victor W. ; Gladding, Robert L. ; Gurney, Mark E. ; Wakabayashi, Yuichi ; Hong, Jinsoo S. ; Manly, Lester S. ; Innis, Robert B. ; Ooms, Maarten ; Morse, Cheryl L. ; Liow, Jeih-San ; D’Amato, Emily C. ; Telu, Sanjay ; Marron, Brian E. ; Sindac, Janice A. ; Fujita, Masahiro ; Nugent, Richard A. ; Zoghbi, Sami S. ; Dick, Rachel M. ; Mo, Xuesheng

We aimed to develop radioligands for PET imaging of brain phosphodiesterase subtype 4D (PDE4D), a potential target for developing cognition enhancing or antidepressive drugs. Exploration of several chemical series gave four leads with high PDE4D inhibitory potency and selectivity, optimal lipophilicity, and good brain uptake. These leads featured alkoxypyridinyl cores. They were successfully labeled with carbon-11 (t_1/2 = 20.4 min) for evaluation with PET in monkey. Whereas two of these radioligands did not provide PDE4D-specific signal in monkey brain, two others, [¹¹C]T1660 and [¹¹C]T1650, provided sizable specific signal, as judged by pharmacological challenge using rolipram or a selective PDE4D inhibitor (BPN14770) and subsequent biomathematical analysis. Specific binding was highest in prefrontal cortex, temporal cortex, and hippocampus, regions that are important for cognitive function. [¹¹C]T1650 was progressed to evaluation in humans with PET, but the output measure of brain enzyme density (V_T) increased with scan duration. This instability over time suggests that radiometabolite(s) were accumulating in the brain. BPN14770 blocked PDE4D uptake in human brain after a single dose, but the percentage occupancy was difficult to estimate because of the unreliability of measuring V_T. Overall, these results show that imaging of PDE4D in primate brain is feasible but that further radioligand refinement is needed, most likely to avoid problematic radiometabolites.

100 项与 11C-T-1650 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
抑郁症	临床2期	美国	National Institute of Mental Health	2019-03-12
认知障碍	临床前	美国	National Institute of Mental Health	2020-03-26
认知障碍	临床前	美国	Tetra Therapeutics Inc.	2020-03-26

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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


NCT03861000 (CTgov)	临床1/2期	抑郁症	3	[C-11]T-1650+BPN14770 (Brain PET Scan With 11C-T-1650 and Blocking With BPN14770)	衊觸壓簾艱窪廠淵艱簾(襯遞艱鬱憲範糧積鏇膚) = 願艱鬱壓淵遞觸範齋範積網廠鹽製獵餘餘憲廠 (餘鏇遞簾醖鏇鏇觸蓋製, 0.91) 更多	-	2021-02-12
				[C-11]T-1650 (Whole Body PET Scan With Intravenous 11C-T-1650)	鬱淵願構壓繭繭網醖積(齋壓襯願簾觸鬱鏇齋積) = 鏇夢鏇選糧壓淵鏇鹽構獵艱壓遞鏇鏇齋襯鑰膚 (艱網鹽願製簾鬱積範繭, 繭廠蓋衊餘觸夢觸獵糧 ~ 壓積網衊夢範鹽顧夢鹽) 更多