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

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

FLUORINE-18 PBR 06, [18F]-FBR-06, [18F]PBR06

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Target

TSPO

Mechanism

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

Therapeutic Areas

Nervous System Diseases

Active Indication

Alzheimer Disease

Inactive Indication

Amyotrophic Lateral SclerosisMultiple SclerosisMultiple System Atrophy

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

Novartis AG

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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.

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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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2

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

PloS oneQ3 · CROSS-FIELD

Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study

Q3 · CROSS-FIELD

ArticleOA

Author: Harty, James P ; Cooper, Michael K ; Thompson, Reid C ; Buck, Jason R ; McKinley, Eliot T ; Abel, Ty W ; Manning, H Charles ; Watchmaker, Jennifer M ; Fu, Allie ; Chambless, Lola

Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes.

Molecules (Basel, Switzerland)

Rapid Purification and Formulation of Radiopharmaceuticals via Thin-Layer Chromatography

Article

Author: van Dam, R Michael ; Laferriere-Holloway, Travis S ; Rios, Alejandra ; Carlucci, Giuseppe

Before formulating radiopharmaceuticals for injection, it is necessary to remove various impurities via purification. Conventional synthesis methods involve relatively large quantities of reagents, requiring high-resolution and high-capacity chromatographic methods (e.g., semi-preparative radio-HPLC) to ensure adequate purity of the radiopharmaceutical. Due to the use of organic solvents during purification, additional processing is needed to reformulate the radiopharmaceutical into an injectable buffer. Recent developments in microscale radiosynthesis have made it possible to synthesize radiopharmaceuticals with vastly reduced reagent masses, minimizing impurities. This enables purification with lower-capacity methods, such as analytical HPLC, with a reduction of purification time and volume (that shortens downstream re-formulation). Still, the need for a bulky and expensive HPLC system undermines many of the advantages of microfluidics. This study demonstrates the feasibility of using radio-TLC for the purification of radiopharmaceuticals. This technique combines high-performance (high-resolution, high-speed separation) with the advantages of a compact and low-cost setup. A further advantage is that no downstream re-formulation step is needed. Production and purification of clinical scale batches of [18F]PBR-06 and [18F]Fallypride are demonstrated with high yield, purity, and specific activity. Automating this radio-TLC method could provide an attractive solution for the purification step in microscale radiochemistry systems.

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	Phase 3	US	Novartis AG	21 Sep 2020
Multiple System Atrophy	Phase 2	US	The Brigham & Women's Hospital, Inc.	24 Mar 2017
Alzheimer Disease	Phase 2	-	National Institute of Mental Health	-
Alzheimer Disease	Phase 2	-	The Brigham & Women's Hospital, Inc.	-
Amyotrophic Lateral Sclerosis	Phase 1	US	Molecular NeuroImaging LLC	28 Jun 2016

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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)	xyxwbwbqon(jtwrcqrfgn) = qicfkhqgqz gamkhiyvtm (mzscuencup ) View more	Positive	07 Dec 2020
				[f-18]pbr06 (Healthy Control)	xyxwbwbqon(jtwrcqrfgn) = pzsrqarnnk gamkhiyvtm (mzscuencup ) View more