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

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

Target

TSPO

Mechanism

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

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication

Diagnostic agentsNeuropsychiatric syndromeAlzheimer Disease+ [1]

Inactive Indication

AIDS Dementia ComplexAtherosclerosisBrain Injuries, Traumatic+ [5]

Originator Organization

The Trustees of Columbia University in The City of New York

Active Organization

University of Texas Health Science Center at Houston

The Trustees of Columbia University in The City of New York

University of Pennsylvania

Inactive Organization

National Institute of Mental Health

AstraZeneca PLC

AbbVie, Inc.

+ [1]

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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]

NCT04490096 / TerminatedPhase 1IIT

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)

Start Date25 Feb 2021

Sponsor / Collaborator

University of Pennsylvania

[+2]

NCT04274998 / RecruitingEarly Phase 1IIT

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.

Start Date03 Mar 2020

Sponsor / Collaborator

University of Pennsylvania

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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14

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

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 ; 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.

01 Nov 2022·Drug Development Research

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

Review

Author: 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.

01 Feb 2022·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

Author: 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 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
Diagnostic agents	Phase 2	-	The Trustees of Columbia University in The City of New York	-
Alzheimer Disease	Preclinical	US	The Brigham & Women's Hospital, Inc.	02 May 2016
Multiple Sclerosis	Preclinical	US	The Brigham & Women's Hospital, Inc.	02 May 2016
Multiple Sclerosis	Preclinical	US	The Brigham & Women's Hospital, Inc.	02 May 2016
Parkinson Disease	Preclinical	SE	AstraZeneca PLC	01 Apr 2012
Brain Injuries, Traumatic	Preclinical	US	National Institute of Mental Health	20 Jan 2012
Inflammation	Preclinical	US	National Institute of Mental Health	20 Jan 2012
Atherosclerosis	Preclinical	US	National Institute of Mental Health	01 Oct 2007
Neurocysticercosis	Preclinical	US	National Institute of Mental Health	04 Sep 2007
Neuroinflammation	Preclinical	US	National Institute of Mental Health	28 Nov 2006

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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)	iekbpylocp(wnawznkntk) = uofmyekdyk ivyrhqdpgp (dsbmqinuii, ltaaoidhmx - vnvvizbdlp) View more	-	30 Jul 2021
				[11C]PBR28 (Repeat Brain PET in Acute TBI Patient)	iekbpylocp(wnawznkntk) = evusvkzaax ivyrhqdpgp (dsbmqinuii, ctfkntleyk - emnqgvenro) View more
Pubmed \| Neurobiol Aging	Not Applicable	Alzheimer Disease 18 kDa translocator protein (TSPO)	-	11C-PBR28	mtufbfckjx(tyurpkckfo) = kamoiciwoa legiqeslsq (gleqrmvset )	-	01 Aug 2016
				11C-PBR28	mtufbfckjx(tyurpkckfo) = rkqaijdqwt legiqeslsq (gleqrmvset )