Delving into the Latest Updates on [18F]-PBR-06 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

+ [1]

Target

TSPO

Action

inhibitors

Mechanism

TSPO inhibitors(Translocator protein inhibitors)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesOther Diseases

Active Indication

Multiple sclerosis relapseAlzheimer Disease

Inactive Indication

Amyotrophic Lateral SclerosisCarotid Artery DiseasesMultiple System Atrophy+ [5]

Originator Organization

The Brigham & Women's Hospital, Inc.

Active Organization

National Institute of Mental Health

The Brigham & Women's Hospital, Inc.

Inactive Organization

Molecular NeuroImaging LLC

Institute for Neurodegenerative Disorders

Centre Hospitalier Universitaire de Bordeaux

+ [1]

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H22FNO4

InChIKeyNSOMTOOLHNHIJA-MIGPCILRSA-N

CAS Registry1003581-94-9

The purpose of this protocol is to create an active natural history cohort of patients with degenerative movement disorders, tracked in a clinical setting with clinical rating scales and neuroimaging. The overarching rationale is that neurodegenerative diseases may be heterogeneous, complex disorders. A new way of performing clinical trials in these patients may be in order and this protocol aims to build a longitudinally tracked clinical trial-ready cohort of patients. The purpose of this protocol is to establish an active natural history cohort of patients with neurodegenerative movement disorders who are deeply phenotyped and "clinical trial ready" across Mass General Brigham.
After a thorough clinical diagnostic evaluation (this may include clinically indicated testing, for example MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, inflammatory tests, skin biopsy) the investigators aim to achieve this through:
Longitudinal tracking of clinical progression through use of clinical scales including at the present time: UMSARS, BARS, MoCA and UPSIT, PROM, MDS-NMS, UPDRS, and SARA
Longitudinal tracking of disease progression through use of neuroimaging including at the present time: TSPO-PET and 3D MRI (see section 1.3)
This is a pilot study designed to track patients with neurodegenerative movement disorders across Mass General Brigham through MRI and PET imaging modalities and clinical measures. Figure 5 represents the study design in detail. In short, subjects will be asked to visit Mass General Brigham every 6-9 months over the course of 18 months for imaging and clinical evaluation.

Start Date01 Mar 2023

Sponsor / Collaborator

The Brigham & Women's Hospital, Inc.

NCT05269446

/ CompletedNot Applicable

Total-body 18F-PBR06 PET/CT to Evaluate Systemic Inflammation and Perfusion in STEMI and SA Patients Receiving PCI

The study will use 18F-PBR06/uExplorer to study the activation of macrophages and systemic perfusion in patients with ST-segment elevation myocardial infarction (STEMI) or stable angina (SA). Participants will receive the total-body PET/CT scan on the seventh day (Day 7, D7) and D180 of enrolment.

Start Date08 Jul 2022

Sponsor / Collaborator

Shanghai Renji Hospital Management Co., Ltd.

NCT04616456

/ CompletedEarly Phase 1IIT

Effect of Verdiperstat on Microglial Activation in Well-characterized MSA Patients

This study will comprise of two phases, an observational phase and a treatment phase.
In the observational phase the specific aims are: 1. To determine the presence and regional distribution of microglial activation, as assessed by 18F-PBR06 PET, in subjects with MSA as compared to healthy controls, at baseline and at 6-9 months' follow-up.
2. To assess the relationship between microglial activation and clinical progression at baseline and follow-up.
In the treatment phase the specific aims of the study are:
The specific aims of the study are:
To assess whether verdiperstat (BHV-3241) reduces 18F-PBR06 PET signal, and thus microglial activation and inflammation, in well-characterized MSA patients.
To assess the relationship between PET changes and clinical progression at baseline and follow-up in patients treated with verdiperstat.
To assess the relationship between PET changes and volumetric brain MRI at baseline and follow-up in patients treated with verdiperstat.
Currently there is no known disease modifying therapy for MSA. Recently, the drug verdiperstat (BHV-3241) has appeared in the investigational arena specifically for the indication of Multiple System Atrophy. Verdiperstat (BHV-3241) is currently being used in a phase 3 active drug trial at Massachusetts Hospital. Verdiperstat (BHV-3241) is known to target Myeloperoxidase, an enzyme implicated in neuroinflammation, a major driver in disease pathogenesis. Our previous study (IRB protocol #2016P002373) demonstrated that applying TSPO (translator protein) PET imaging enabled us to track changes in neuroinflammation and thus provide a viable biomarker for disease progression.
In this pilot study, the investigators aim to assess the effect of an investigational drug, verdiperstat (BHV-3241) on microglial activation in MSA patients using [F-18]PBR06 and to link it with clinical and morphometric MRI brain changes following treatment.

Start Date30 Dec 2020

Sponsor / Collaborator

The Brigham & Women's Hospital, Inc.

[+1]

100 Clinical Results associated with [18F]-PBR-06

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100 Translational Medicine associated with [18F]-PBR-06

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100 Patents (Medical) associated with [18F]-PBR-06

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19

Literatures (Medical) associated with [18F]-PBR-06

01 Jan 2023·Journal of Chromatography A

A rapid and systematic approach for the optimization of radio thin-layer chromatography resolution

Article

Author: Rios, Alejandra ; Laferriere-Holloway, Travis S ; van Dam, R Michael ; Lu, Yingqing ; Okoro, Chelsea C

Radiopharmaceutical analysis is limited by conventional methods. Radio-HPLC may be inaccurate for some compounds (e.g., ¹⁸F-radiopharmaceuticals) due to radionuclide sequester. Radio-TLC is simpler, faster, and detects all species but has limited resolution. Imaging-based readout of TLC plates (e.g., using Cerenkov luminescence imaging) can improve readout resolution, but the underlying chromatographic separation efficiency may be insufficient to resolve chemically similar species such as product and precursor-derived impurities. This study applies a systematic mobile phase optimization method, PRISMA, to improve radio-TLC resolution. The PRISMA method optimizes the mobile phase by selecting the correct solvent, optimizing solvent polarity, and optimizing composition. Without prior knowledge of impurities and by simply observing the separation resolution between a radiopharmaceutical and its nearest radioactive or non-radioactive impurities (observed via UV imaging) for different mobile phases, the PRISMA method enabled the development of high-resolution separation conditions for a wide range of ¹⁸F-radiopharmaceuticals ( [¹⁸F]PBR-06, [¹⁸F]FEPPA, [¹⁸F]Fallypride, [¹⁸F]FPEB, and [¹⁸F]FDOPA). Each optimization required a single batch of crude radiopharmaceutical and a few hours. Interestingly, the optimized TLC method provided greater accuracy (compared to other published TLC methods) in determining the product abundance of one radiopharmaceutical studied in more depth ( [¹⁸F]Fallypride) and was capable of resolving a comparable number of species as isocratic radio-HPLC. We used the PRISMA-optimized mobile phase for [¹⁸F]FPEB in combination with multi-lane radio-TLC techniques to evaluate reaction performance during high-throughput synthesis optimization of [¹⁸F]FPEB. The PRISMA methodology, in combination with high-resolution radio-TLC readout, enables a rapid and systematic approach to achieving high-resolution and accurate analysis of radiopharmaceuticals without the need for radio-HPLC.

01 Dec 2021·EJNMMI ResearchQ3 · MEDICINE

In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease

Q3 · MEDICINE

ArticleOA

Author: Zhang, Andrea ; Innis, Robert B ; Schollhammer, Romain ; Sibon, Igor ; Rullier, Anne ; Zanotti-Fregonara, Paolo ; Vimont, Delphine ; Fujita, Masahiro ; Morgat, Clément ; Lepreux, Sébastien ; Barthe, Nicole ; Berard, Xavier ; Kimura, Yasuyuki

AbstractBackgroundInflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28.ResultsAll in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants.ConclusionDespite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease.Trial registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov.

01 Aug 2019·Molecular Imaging and BiologyQ3 · MEDICINE

Monitoring the Progression of Chronic Liver Damage in Rats Using [18F]PBR06

Q3 · MEDICINE

Article

Author: Guo, Jun ; Li, Chao ; Liang, Sheng ; Wang, Hui ; Wu, Shuqi ; Huang, Shuo ; Zhang, Linlin

PURPOSEAccurate and rapid assessment of liver condition is the key to therapy for hepatitis patients. This study aim is to evaluate the peripheral benzodiazepine receptor (PBR) radioligand [¹⁸F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([¹⁸F]PBR06) as a positron emission tomography (PET) imaging tracer of chronic liver damage in a rat model.PROCEDURESA rat model of liver damage was made by bile duct ligation (BDL), which initiates a complex cascade of pathological events that leads to cholestasis and inflammation, eventually resulting in a severe fibrotic and severe hepatocyte injury. PET scanning, immunofluorescence staining, H&E staining, Masson's staining, and Quantitative real time polymerase chain reaction(qRT-PCR) were performed to elucidate the correlation among the expression level of PBR, radioactivity uptake, and the level of liver damage in the rat model of chronic inflammatory.RESULTSAlanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) increased after BDL and peaked in 1 week, then gradually decreased over the following 3 weeks, although still higher than that of control (all P < 0.05). Histological analysis demonstrated chronic severe damage in rat livers after BDL. The uptake of [¹⁸F]PBR06 increased in livers and was correlated with severity of liver damage. Further, the mRNA level of PBR was obviously higher compared to controls.CONCLUSIONS[¹⁸F]PBR06 can serve as a sensitive probe to monitor the progression of inflammation in liver. [¹⁸F]PBR06 imaging may be used to accurately assess liver damage degree and guide the therapeutic schedule, especially for those patients with severe liver inflammation and damage but with normal or mildly elevated serum ALT and AST. As a non-invasive diagnostic application, [¹⁸F]PBR06 PET scan could be an alternative for patients who is unwilling to perform liver biopsy.

100 Deals associated with [18F]-PBR-06

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple sclerosis relapse	Phase 3	United States	The Brigham & Women's Hospital, Inc.	21 Sep 2020
Alzheimer Disease	Phase 2	-	The Brigham & Women's Hospital, Inc.	-
Alzheimer Disease	Phase 2	-	National Institute of Mental Health	-
Multiple Sclerosis	Phase 1	United States	Novartis AG	21 Sep 2020
Multiple System Atrophy	Phase 1	United States	The Brigham & Women's Hospital, Inc.	24 Mar 2017
Amyotrophic Lateral Sclerosis	Phase 1	United States	Molecular NeuroImaging LLC	28 Jun 2016
Multiple Sclerosis	Preclinical	United States	Novartis AG	21 Sep 2020
Carotid Artery Diseases	Preclinical	France	Centre Hospitalier Universitaire de Bordeaux	18 Sep 2017
Stroke	Preclinical	France	Centre Hospitalier Universitaire de Bordeaux	18 Sep 2017
Parkinson Disease	Preclinical	United States	Institute for Neurodegenerative Disorders	01 Nov 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ECTRIMS2020	Not Applicable	Multiple Sclerosis [F-18]PBR06-Positron Emission Tomography (PET)	22	[f-18]pbr06 (Multiple Sclerosis)	rqrtwzdbba(zfjpwqxqpt) = gzefyfdzxl nytxksotdt (nnfpredaji ) View more	Positive	07 Dec 2020
				[f-18]pbr06 (Healthy Control)	rqrtwzdbba(zfjpwqxqpt) = mbcotrnlhr nytxksotdt (nnfpredaji ) View more