[11C]PBR-28([11C]PBR-28) - 药物靶点：TSPO_在研适应症：艾滋病痴呆复合征，神经精神综合征，阿尔茨海默症_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

靶点

TSPO

作用方式

抑制剂、增强剂

作用机制

TSPO抑制剂(TSPO蛋白抑制剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

免疫系统疾病感染神经系统疾病+ [2]

在研适应症

艾滋病痴呆复合征神经精神综合征阿尔茨海默症+ [1]

非在研适应症

动脉粥样硬化创伤性脑损伤颈动脉疾病+ [3]

原研机构

The Trustees of Columbia University in The City of New York

在研机构

National Institutes of Health

University of Pennsylvania

University of Texas Health Science Center at Houston

非在研机构

AstraZeneca PLC

National Institute of Mental Health

AbbVie, Inc.

+ [1]

最高研发阶段临床1/2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C21H20N2O3

InChIKeyDHZBNHMEIOBPAE-JVVVGQRLSA-N

CAS号1005325-43-8

关联

17

项与 [11C]PBR-28 相关的临床试验

NCT05586581

/ Recruiting临床1/2期IIT

PET Imaging of Synaptic Density Combined with Neuroimmunologic Measures to Reveal Mechanisms of HIV Neuropathogenesis During ART

The purpose of this study is to longitudinally characterize and evaluate changes in synaptic density in the brain using novel positron-emission tomography (PET) scans; magnetic resonance imaging (MRI), and clinical laboratory markers associated with HIV-related injury in the central nervous system. This study will test hypotheses relating to the presence and mechanisms of aberrant brain structure at the synaptic level in living humans with virologically controlled HIV on antiretroviral therapy. To evaluate associations between PET imaging radiotracers [11C]UCB-J, a ligand for presynaptic vesicle protein 2A (SV2A), a vesicle membrane protein expressed in synapses, and PET [11C]PBR28 a measure of microglia function in the brain, the Yale PET center has developed an advanced approach of combining multiple distinct ligands in coordinated same-day PET imaging. Additionally, the study will evaluate the associations of this novel synaptic density marker with well-established clinical measures of neurocognitive performance and laboratory measures of blood and cerebrospinal fluid (CSF).

开始日期2023-05-17

申办/合作机构

Yale University

[+2]

NCT05205291

/ RecruitingN/AIIT

Molecular Imaging of LPS-induced Microglial Activation in Parkinson's Disease (PD). a TSPO PET-MR Imaging Study

It is not known what causes Parkinson's disease and what makes it worsen over time. Research conducted in the past few years has highlighted the possible role of inflammation on this process but its actual mechanisms are still obscure.
In this study, the investigators aim to gain understanding on how inflammation is increased in Parkinson's disease and what are its mechanisms, by performing two Positron Emission Tomography (PET) scans using the tracer [11C]PBR28, that takes pictures of the brain highlighting the areas of inflammation, before and after the administration of a compound called Lipopolysaccharide or LPS, that is known to cause a mild degree of inflammation. The investigators will couple this study with two venous blood draws to measure the levels of circulating molecules of inflammation.

开始日期2022-02-28

申办/合作机构

The University of Exeter

NCT04398719

/ Recruiting早期临床1期IIT

Effect of Cannabidiol on Microglial Activation and Central Pain-Sensitization

This study aims to examine the effect of cannabidiol (CBD) pre-treatment on brain microglial activation in healthy human subjects. Secondarily, this study aims to examine the effect of cannabidiol (CBD) pre-treatment on central pain-sensitization in healthy human subjects.

开始日期2021-05-07

申办/合作机构

Yale University

[+1]

100 项与 [11C]PBR-28 相关的临床结果

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100 项与 [11C]PBR-28 相关的转化医学

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100 项与 [11C]PBR-28 相关的专利（医药）

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119

项与 [11C]PBR-28 相关的文献（医药）

2024-08-27·Proceedings of the National Academy of Sciences

Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia

Article

作者: Davis, Margaret T. ; Huang, Yiyun ; Cosgrove, Kelly P. ; Esterlis, Irina ; Hillmer, Ansel T. ; Bhatt, Shivani ; Krystal, John H. ; Woodcock, Eric ; Nabulsi, Nabeel ; Bonomi, Robin ; Angarita, Gustavo A. ; Rusowicz, Aleksandra ; Pietrzak, Robert H. ; Carson, Richard E.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [ 11 C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls. The PTSD group exhibited a significantly lower magnitude LPS-induced increase in TSPO availability in an a priori prefrontal-limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte–macrophage colony-stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self-reported sickness symptoms did not differ between groups; these findings highlight group differences in central–peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia-mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease.

2024-07-05·Brain

Characterization of cortico-meningeal translocator protein expression in multiple sclerosis

Article

作者: Treaba, Constantina A ; Klawiter, Eric C ; Babu, Suma ; Mainero, Caterina ; Makary, Meena M ; Sloane, Jacob A ; Magliozzi, Roberta ; Kinkel, Revere P ; Ouellette, Russell ; Catana, Ciprian ; Mastantuono, Marina ; Herranz, Elena ; Barletta, Valeria T ; Magon, Stefano ; Hooker, Jacob M ; Nicholas, Richard ; Loggia, Marco L ; Ionete, Carolina ; Mehndiratta, Ambica

AbstractCompartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry.Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60–90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors.Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis.Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease.

2024-07-01·Brain, Behavior, and Immunity

Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures

Article

作者: Bues, Hannah F ; Dougherty, Darin D ; Loggia, Marco L ; Saadi, Deena ; Ratai, Eva-Maria ; VanElzakker, Michael B ; Brusaferri, Ludovica ; Kim, Minhae

The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [¹¹C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.

100 项与 [11C]PBR-28 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
阿尔茨海默症	临床3期	美国	The Brigham & Women's Hospital, Inc.	2016-05-02
多发性硬化症	临床3期	美国	The Brigham & Women's Hospital, Inc.	2016-05-02
帕金森病	临床3期	瑞典	AstraZeneca PLC	2012-04-01
创伤性脑损伤	临床3期	美国	National Institute of Mental Health	2012-01-20
炎症	临床3期	美国	National Institute of Mental Health	2012-01-20
颈动脉疾病	临床3期	美国	National Institute of Mental Health	2007-10-01
神经系统囊虫病	临床3期	美国	National Institute of Mental Health	2007-09-04
神经炎症	临床3期	美国	National Institute of Mental Health	2006-11-28
艾滋病痴呆复合征	临床2期	美国	National Institutes of Health	2023-05-17
多发性硬化症	临床前	美国	The Brigham & Women's Hospital, Inc.	2016-05-02

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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


NCT01547780 (CTgov)	临床1/2期	炎症 \| 创伤性脑损伤	52	[11C]PBR28 (Baseline Brain PET in Acute TBI Patient)	鬱鹹艱醖網範齋窪鹹憲(繭糧範築鬱膚醖餘衊憲) = 衊廠襯夢窪鑰齋蓋餘衊顧遞選築願觸築鹽廠鹹 (襯廠鏇餘顧蓋範糧選醖, 窪網餘觸壓獵膚鬱網觸 ~ 觸鏇願蓋膚構範繭餘糧) 更多	-	2021-07-30
				[11C]PBR28 (Repeat Brain PET in Acute TBI Patient)	鬱鹹艱醖網範齋窪鹹憲(繭糧範築鬱膚醖餘衊憲) = 齋觸艱網餘築獵蓋遞鬱顧遞選築願觸築鹽廠鹹 (襯廠鏇餘顧蓋範糧選醖, 艱鹹鬱鏇鹹淵蓋夢鬱觸 ~ 蓋鹽膚鬱衊糧蓋鹽醖淵) 更多
ECTRIMS2018	N/A	多发性硬化症 TSPO \| rs6971 genotypes	-	[18F]GE-180 ([18F]GE-180)	積鑰鹽鏇蓋觸觸廠獵夢(範窪觸夢網繭窪膚廠遞) = 淵鹽壓願鏇範鹹齋鹽艱願築網餘遞顧齋窪窪鹹 (齋獵鑰顧顧齋積範醖艱, 0.02 ~ 0.16) 更多	-	2018-10-09
				[11C]PBR28 ([11C]PBR28)	積鑰鹽鏇蓋觸觸廠獵夢(範窪觸夢網繭窪膚廠遞) = 齋遞鏇積願網獵獵願淵願築網餘遞顧齋窪窪鹹 (齋獵鑰顧顧齋積範醖艱, 3.02 ~ 4.21) 更多
NCT00955422 \| NCT00613119 (Pubmed \| Neurobiol Aging)	N/A	阿尔茨海默症 18 kDa translocator protein (TSPO)	-	11C-PBR28	壓廠積襯積構繭餘願獵(蓋製糧鑰鬱蓋淵鹹膚範) = 鬱鹽願願築蓋範壓鑰艱顧顧醖衊鑰繭網膚餘醖 (艱餘蓋鬱簾艱窪築網壓 )	-	2016-08-01
				11C-PBR28	壓廠積襯積構繭餘願獵(蓋製糧鑰鬱蓋淵鹹膚範) = 糧觸觸觸選糧醖鏇膚壓顧顧醖衊鑰繭網膚餘醖 (艱餘蓋鬱簾艱窪築網壓 )
AAI2015	N/A	胰腺癌	-	[11C]PBR28 (Wild-type mice)	衊淵淵衊鹹網糧網鹽觸(鏇膚顧鑰醖鬱鏇遞獵淵) = 淵鹹範繭窪艱艱鏇顧範繭範鹽壓齋願醖範醖餘 (廠襯獵憲顧衊壓衊顧願 )	-	2015-05-01
SNMMI2014	N/A	癫痫	-	[11C]DPA-713	遞鑰鏇觸鑰鑰齋蓋遞選(蓋糧壓繭構願鹽觸糧膚) = 夢艱糧襯選顧憲衊餘鹹膚顧蓋顧膚憲製餘夢壓 (積淵醖鏇糧繭淵鹹憲鑰 )	-	2014-11-05
				[11C]PBR28[11C]DPA-713 ([11C]PBR28)	遞鑰鏇觸鑰鑰齋蓋遞選(蓋糧壓繭構願鹽觸糧膚) = 範構製顧齋願餘憲觸憲膚顧蓋顧膚憲製餘夢壓 (積淵醖鏇糧繭淵鹹憲鑰 )