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+ [1]

Active Indication

AIDS Dementia ComplexNeuropsychiatric syndrome

Inactive Indication

Alzheimer DiseaseAtherosclerosisCarotid Artery Diseases+ [4]

Originator Organization

The Trustees of Columbia University in The City of New York

Active Organization

National Institutes of Health

University of Texas Health Science Center at Houston

Inactive Organization

AstraZeneca PLC

AbbVie, Inc.

National Institute of Mental Health

+ [1]

License Organization-

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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118

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 ; Makary, Meena M ; Mainero, Caterina ; 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

Mild and deep hypothermia differentially affect cerebral neuroinflammatory and cold shock response following cardiopulmonary bypass in rat

Article

Author: Jongman, Rianne M ; Nieuwenhuijs-Moeke, Gertrude J ; Bosch, Dirk J ; Henning, R H ; Doorduin, Janine ; Jainandunsing, Jayant ; Stern, Manon ; Absalom, Anthony R ; Kok, Wendelinde F

INTRODUCTIONTargeted temperature management (TTM) is considered to be a neuroprotective strategy during cardiopulmonary bypass (CPB) assisted procedures, possibly through the activation of cold shock proteins. We therefore investigated the effects of mild compared with deep hypothermia on the neuroinflammatory response and cold shock protein expression after CPB in rats.METHODSWistar rats were subjected to 1 hr of mild (33 °C) or deep (18 °C) hypothermia during CPB or sham procedure. PET scan analyses using TSPO ligand [¹¹C]PBR28 were performed on day 1 (short-term) or day 3 and 7 post-procedure (long-term) to assess neuroinflammation. Hippocampal and cortical samples were obtained at day 1 in the short-term group and at day 7 in the long-term group. mRNA expression of M1 and M2 microglia associated cytokines was analysed with RT-PCR. Cold shock protein RNA-binding motive 3 (RBM3) and tyrosine receptor kinase B (TrkB) receptor protein expression were determined with Western Blot and quantified.RESULTSIn both groups target temperature was reached within an hour. Standard uptake values (SUV) of [¹¹C]PBR28 in CPB rats at 1 day and 3 days were similar to that of sham animals. At 7 days after CPB the SUV was significantly higher in amygdala and hippocampal regions of the CPB 18 °C group as compared to the CPB 33 °C group. No differences were observed in the expression of M1 and M2 microglia-related cytokines between TTM 18 °C and 33 °C. RBM3 protein levels in cortex and hippocampus were significantly higher in CPB 33 °C compared to CPB 18 °C and sham 33 °C, at day 1 and day 7, respectively.CONCLUSIONSTTM at 18 °C increased the neuroinflammatory response in amygdala and hippocampus compared to TTM at 33 °C in rats undergoing a CPB procedure. Additionally, TTM at 33 °C induced increased expression of TrkB and RBM3 in cortex and hippocampus of rats on CPB compared to TTM at 18 °C. Together, these data indicate that neuroinflammation is alleviated by TTM at 33 °C, possibly by recruiting protective mechanisms through cold shock protein induction.

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
Atherosclerosis	Phase 3	United States	National Institute of Mental Health	01 Oct 2007
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
Neuropsychiatric syndrome	Phase 1	United States	University of Texas Health Science Center at Houston	01 May 2017
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)	ydkuxgfubw(dkbfjdxans) = oozlspwnom aqfkeiggnm (lfkydaosrv, kxmhobrkwx - rjggnirctr) View more	-	30 Jul 2021
				[11C]PBR28 (Repeat Brain PET in Acute TBI Patient)	ydkuxgfubw(dkbfjdxans) = rdaulaqjrj aqfkeiggnm (lfkydaosrv, lzyqwrysnf - nacydcohvc) View more
ECTRIMS2018	Not Applicable	Multiple Sclerosis TSPO \| rs6971 genotypes	-	[18F]GE-180 ([18F]GE-180)	uyenfwfoxi(kcbtnczana) = lskdutmxxb vyplpuktak (velkdskxzo, 0.02 - 0.16) View more	-	09 Oct 2018
				[11C]PBR28 ([11C]PBR28)	uyenfwfoxi(kcbtnczana) = oijwyxyecy vyplpuktak (velkdskxzo, 3.02 - 4.21) View more
AAI2015	Not Applicable	Pancreatic Cancer	-	[11C]PBR28 (Wild-type mice)	byhvwbxzsm(bubflhmoyn) = rjailzgxlz cllgsjyhvn (scuiolppwg )	-	01 May 2015
SNMMI2014	Not Applicable	Epilepsy	-	[11C]DPA-713	qjldehvwog(cntfvfiynm) = ijlvecdpyl dfxnukoqzl (znkrowuzai )	-	05 Nov 2014
				[11C]PBR28[11C]DPA-713 ([11C]PBR28)	qjldehvwog(cntfvfiynm) = yqymwkrjff dfxnukoqzl (znkrowuzai )