[11C]PBR-28([11C]PBR-28) - 药物靶点：TSPO_在研适应症：诊断试剂，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

其他疾病神经系统疾病

在研适应症

诊断试剂神经精神综合征阿尔茨海默症+ [1]

非在研适应症

艾滋病痴呆复合征动脉粥样硬化创伤性脑损伤+ [5]

原研机构

The Trustees of Columbia University in The City of New York

在研机构

University of Texas Health Science Center at Houston

The Trustees of Columbia University in The City of New York

University of Pennsylvania

非在研机构

National Institute of Mental Health

AstraZeneca PLC

AbbVie, Inc.

+ [1]

最高研发阶段临床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

分子式C21H20N2O3

InChIKeyDHZBNHMEIOBPAE-JVVVGQRLSA-N

CAS号1005325-43-8

关联

13

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]

NCT04490096 / Terminated临床1期IIT

Multimodal Imaging Outcome Measures for ALS (Image ALS)

The primary aim of this study is to determine whether longitudinal neuroimaging acquired across multiple research and clinical centers is a feasible biomarker to use as an outcome measure for clinical trials in amyotrophic lateral sclerosis (ALS)

开始日期2021-02-25

申办/合作机构

University of Pennsylvania

[+2]

NCT04274998 / Recruiting早期临床1期IIT

Evaluation of in Vivo Neuroinflammation in Alzheimer's Disease Using Novel Positron Emission Tomography (PET/CT) Imaging

This research study is being done to learn more about inflammation in the brain using Positron Emission Tomography/Computed Tomography (PET/CT) imaging in people with Alzheimer's Disease/Mild Cognitive Impairment or healthy controls.
If the subject agrees to be in this study, she/ he will have a PET/CT scan using the investigational radiotracer [18F]NOS. A subject with a specific genetic polymorphism may also agree to be in the sub-study in which she/he will have another PET/CT scan using the investigational tracer [11C]PBR28 for comparison with the FNOS [18F]NOS scan. For subjects who agree to this sub-study they may undergo the brain PET/CT scan with [11C]PBR28 either on the same day as the [18F]NOS PET/CT or on another day. The subject may have a screening visit before the PET/CT scan visit if the investigator needs to confirm the subject is able to be in the study.
A blood sample will be taken before the scans. Additional blood samples will be taken during the PET scans. Subjects must also agree to have an MRI scan for this research study if she/he has not had a recent scan that the study doctor decides can be used for this study.

开始日期2020-03-03

申办/合作机构

University of Pennsylvania

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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14

项与 [11C]PBR-28 相关的文献（医药）

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 ; Makary, Meena M ; Mainero, Caterina ; Sloane, Jacob A ; Kinkel, Revere P ; Magliozzi, Roberta ; 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.

2022-11-01·Drug Development Research

Acetamidobenzoxazolone scaffold as a promising translocator protein (18 kDa, TSPO) marker for neuroinflammation imaging: Advancement in last decennial period

Review

作者: Tiwari, Anjani Kumar ; Zhang, Ming‐Rong ; Adhikari, Anupriya

AbstractInflammation has been linked to the onset and progression of a wide range of neuropathological disorders. The well‐conserved outer mitochondrial membrane 18 kDa translocator protein (TSPO) is perceived as an in vivo neuroinflammation marker. A dearth of a reference region, genetic disparity influencing the ligand's affinity for TSPO, and a substantial signal in the endothelium of the brain veins contributes toward complications in quantifying TSPO positron emission tomography (PET) image. Up to the present time several radiotracers based on different pharmacophore such as (R)[11C]PK11195, [18F]DPA714, [11C]PBR28, [11C]ER176, and many more have been recognized for envisaging the prominent TSPO level observed in neurological conditions. Recently acetamidobenzoxazolone (ABO) scaffold, a bicyclic ring system composed of a phenyl ring fused to a carbamate and its substituted radiolabelled analogues especially at C‐5 position has evidenced encouraging outcomes as next generation of TSPO PET ligands. Diverse ABO framework‐based TSPO ligands have been designed embracing imperative aspects such as lipophilicity, metabolic profile, and capability to penetrate the blood–brain barrier apart from least effect of polymorphism (rs6971). Over the years numerous systematic literature reviews compiling different structural class of TSPO ligands characterized on the grounds of their binding affinity and metabolite profile have been reported but none is especially focused toward a fascinating benzoxazolone scaffold. This review exclusively bestows an overview of the recent advancements on ABO derivatives with neuroinflammation imaging potential and emphases on the structural features accountable for visualizing TSPO in‐vivo with collation of published reports during last 10 years.

2022-02-01·Molecular Imaging and Biology

Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls

Article

作者: Krzyczmonik, Anna ; Damont, Annelaure ; Bocancea, Diana ; Dollé, Frédéric ; Helin, Jatta S ; Helin, Semi ; López-Picón, Francisco R ; Solin, Olof ; Keller, Thomas ; Haaparanta-Solin, Merja ; Rinne, Juha O

AbstractPurposeIn this study we compared the recently developed TSPO tracer [18F]F-DPA, with [18F]DPA-714 and [11C]PBR28 by performing in vivo PET imaging on the same Alzheimer’s disease mouse model APP/PS1-21 (TG) and wild-type (WT) mice with all three radiotracers.ProceduresTo compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVRCB), and voxel-wise analyses were performed.ResultsThe peak uptake of [18F]F-DPA was higher than 4.3% ID/mL, while [18F]DPA-714 reached just over 3% ID/mL, and [11C]PBR28 was over 4% ID/mL in only one brain region in the WT mice. The peak/60-min uptake ratios of [18F]F-DPA were significantly higher (p < 0.001) than those of [18F]DPA-714 and [11C]PBR28. The differences in [18F]F-DPA SUVRCB between WT and TG mice were highly significant (p < 0.001) in the three studied time periods after injection. [18F]DPA-714 uptake was significantly higher in TG mice starting in the 20–40-min timeframe and increased thereafter, whereas [11C]PBR28 uptake became significant at 10–20 min (p < 0.05). The voxel-wise analysis confirmed the differences between the radiotracers.Conclusions[18F]F-DPA displays higher brain uptake, higher TG-to-WT SUVRCB ratios, and faster clearance than [18F]DPA-714 and [11C]PBR28, and could prove useful for detecting low levels of inflammation and allow for shorter dynamic PET scans.

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
诊断试剂	临床2期	-	The Trustees of Columbia University in The City of New York	-
阿尔茨海默症	临床前	美国	The Brigham & Women's Hospital, Inc.	2016-05-02
多发性硬化症	临床前	美国	The Brigham & Women's Hospital, Inc.	2016-05-02
多发性硬化症	临床前	美国	The Brigham & Women's Hospital, Inc.	2016-05-02
帕金森病	临床前	瑞典	AstraZeneca PLC	2012-04-01
创伤性脑损伤	临床前	美国	National Institute of Mental Health	2012-01-20
炎症	临床前	美国	National Institute of Mental Health	2012-01-20
动脉粥样硬化	临床前	美国	National Institute of Mental Health	2007-10-01
神经系统囊虫病	临床前	美国	National Institute of Mental Health	2007-09-04
神经炎症	临床前	美国	National Institute of Mental Health	2006-11-28

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临床结果

适应症

分期

评价

查看全部结果

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)	鹹積衊觸遞築鬱鏇獵網(遞選製構鹽網鹹築糧夢) = 構蓋網鹹膚膚夢鹹醖鹹鏇糧鹹夢顧餘製蓋襯衊 (壓遞壓積觸顧醖壓醖鹹, 糧夢夢餘醖繭願窪夢網 ~ 憲廠廠齋壓遞網壓鏇製) 更多	-	2021-07-30
				[11C]PBR28 (Repeat Brain PET in Acute TBI Patient)	鹹積衊觸遞築鬱鏇獵網(遞選製構鹽網鹹築糧夢) = 鹽衊網餘膚齋窪遞觸糧鏇糧鹹夢顧餘製蓋襯衊 (壓遞壓積觸顧醖壓醖鹹, 廠蓋窪憲鏇遞淵廠鏇遞 ~ 構鹹願鏇窪襯鬱膚網糧) 更多
Pubmed \| Neurobiol Aging	N/A	阿尔茨海默症 18 kDa translocator protein (TSPO)	-	11C-PBR28	膚築遞艱範簾襯觸鏇遞(齋遞選鏇鏇窪蓋夢鑰範) = 顧衊網築築製鹹醖壓窪齋鹹範獵鏇觸膚鬱簾窪 (壓衊夢願選鬱顧廠觸衊 )	-	2016-08-01
				11C-PBR28	膚築遞艱範簾襯觸鏇遞(齋遞選鏇鏇窪蓋夢鑰範) = 遞鹽蓋鬱鏇簾齋觸鏇膚齋鹹範獵鏇觸膚鬱簾窪 (壓衊夢願選鬱顧廠觸衊 )