Delving into the Latest Updates on [11C]PBR-28 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

Target

TSPO

Action

inhibitors, enhancers

Mechanism

TSPO inhibitors(Translocator protein inhibitors), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesNervous System Diseases+ [2]

Active Indication

AIDS Dementia ComplexNeuropsychiatric syndromeAlzheimer Disease+ [1]

Inactive Indication

AtherosclerosisBrain Injuries, TraumaticCarotid Artery Diseases+ [3]

Originator Organization

The Trustees of Columbia University in The City of New York

Active Organization

National Institutes of Health

University of Pennsylvania

University of Texas Health Science Center at Houston

Inactive Organization

AstraZeneca PLC

National Institute of Mental Health

AbbVie, Inc.

+ [1]

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC21H20N2O3

InChIKeyDHZBNHMEIOBPAE-JVVVGQRLSA-N

CAS Registry1005325-43-8

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).

Start Date17 May 2023

Sponsor / Collaborator

Yale University

[+2]

NCT05205291

/ RecruitingNot ApplicableIIT

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.

Start Date28 Feb 2022

Sponsor / Collaborator

The University of Exeter

NCT04398719

/ RecruitingEarly Phase 1IIT

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.

Start Date07 May 2021

Sponsor / Collaborator

Yale University

[+1]

100 Clinical Results associated with [11C]PBR-28

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100 Translational Medicine associated with [11C]PBR-28

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100 Patents (Medical) associated with [11C]PBR-28

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119

Literatures (Medical) associated with [11C]PBR-28

27 Aug 2024·Proceedings of the National Academy of Sciences

Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia

Article

Author: 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.

05 Jul 2024·Brain

Characterization of cortico-meningeal translocator protein expression in multiple sclerosis

Article

Author: 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.

01 Jul 2024·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

Author: 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 Deals associated with [11C]PBR-28

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 3	United States	The Brigham & Women's Hospital, Inc.	02 May 2016
Multiple Sclerosis	Phase 3	United States	The Brigham & Women's Hospital, Inc.	02 May 2016
Parkinson Disease	Phase 3	Sweden	AstraZeneca PLC	01 Apr 2012
Brain Injuries, Traumatic	Phase 3	United States	National Institute of Mental Health	20 Jan 2012
Inflammation	Phase 3	United States	National Institute of Mental Health	20 Jan 2012
Carotid Artery Diseases	Phase 3	United States	National Institute of Mental Health	01 Oct 2007
Neurocysticercosis	Phase 3	United States	National Institute of Mental Health	04 Sep 2007
Neuroinflammation	Phase 3	United States	National Institute of Mental Health	28 Nov 2006
AIDS Dementia Complex	Phase 2	United States	National Institutes of Health	17 May 2023
Multiple Sclerosis	Preclinical	United States	The Brigham & Women's Hospital, Inc.	02 May 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01547780 (CTgov)	Phase 1/2	Inflammation \| Brain Injuries, Traumatic	52	[11C]PBR28 (Baseline Brain PET in Acute TBI Patient)	qcvqtxqnhh(zvcyurtwev) = cgzqhwszfd wymwcdnxwa (jbtfukpljc, ujdfklcvpe - cfjvbnrfko) View more	-	30 Jul 2021
				[11C]PBR28 (Repeat Brain PET in Acute TBI Patient)	qcvqtxqnhh(zvcyurtwev) = cwdotmfnxb wymwcdnxwa (jbtfukpljc, ebfvrykjfl - igtqcaxklc) View more
ECTRIMS2018	Not Applicable	Multiple Sclerosis TSPO \| rs6971 genotypes	-	[18F]GE-180 ([18F]GE-180)	vpiedwgrfe(jdqiprdokt) = sfjuoxcaon qplptojqep (fxpqpabbcg, 0.02 - 0.16) View more	-	09 Oct 2018
				[11C]PBR28 ([11C]PBR28)	vpiedwgrfe(jdqiprdokt) = alogxtujvy qplptojqep (fxpqpabbcg, 3.02 - 4.21) View more
NCT00955422 \| NCT00613119 (Pubmed \| Neurobiol Aging)	Not Applicable	Alzheimer Disease 18 kDa translocator protein (TSPO)	-	11C-PBR28	vgoofftlcj(awwxzpdfiw) = caybzqzcku nafykyaghu (wlgkkxdcym )	-	01 Aug 2016
				11C-PBR28	vgoofftlcj(awwxzpdfiw) = rjzqgjnkdx nafykyaghu (wlgkkxdcym )
AAI2015	Not Applicable	Pancreatic Cancer	-	[11C]PBR28 (Wild-type mice)	mfjxfehwol(bhybfkejtw) = ywymdtnqyc roiovsvaig (ifghnsghcs )	-	01 May 2015
SNMMI2014	Not Applicable	Epilepsy	-	[11C]DPA-713	vmvnhvoise(qurpvbfsbe) = dfulwjtoiv hkusozpvdk (actidcxfvz )	-	05 Nov 2014
				[11C]PBR28[11C]DPA-713 ([11C]PBR28)	vmvnhvoise(qurpvbfsbe) = fgyepbsnum hkusozpvdk (actidcxfvz )