Abstract
The vesicular acetylcholine transporter (VAChT) is a glycoprotein responsible for the accumulation of acetylcholine into pre-synaptic vesicules of cholinergic neurons. Cholinergic innervation has been shown to be decreased at the earlier stages of Alzheimer's disease (AD). Thus, the expression of VAChT has been correlated with the severity of the dementia and has been considered as a significant diagnostic target for AD. To this end numerous radioligands based on the vesamicol scaffold have been developed for imaging the VAChT using positron emission tomography (PET). Among the various radioligands only a small number have been evaluated in vivo in non-human primate and human. Despite promising in vitro, ex vivo and first in vivo studies, most of them are unsuitable for clinical use in humans due to poor selectivity over σ receptors, low extraction from the blood, slow brain kinetics or fast metabolism. To date (-)-[11C]OMV (1), (-)-[11C]MABV (2), (-)-[18F]-FEOBV (6), (-)-trans-2-hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidine) tetralin (8) and [18F]FBMV (12) are promising radioligands for the VAChT, though further validation is required to confirm their clinical usefulness.
Keywords: VAChT, Alzheimer’s disease, benzovesamicol, positron emission tomography, fluorine-18, carbon-11, PET.
Current Topics in Medicinal Chemistry
Title: PET Radioligands for the Vesicular Acetylcholine Transporter (VAChT)
Volume: 10 Issue: 15
Author(s): Nicolas Giboureau, Ian Mat Som, Aurelie Boucher-Arnold, Denis Guilloteau and Michael Kassiou
Affiliation:
Keywords: VAChT, Alzheimer’s disease, benzovesamicol, positron emission tomography, fluorine-18, carbon-11, PET.
Abstract: The vesicular acetylcholine transporter (VAChT) is a glycoprotein responsible for the accumulation of acetylcholine into pre-synaptic vesicules of cholinergic neurons. Cholinergic innervation has been shown to be decreased at the earlier stages of Alzheimer's disease (AD). Thus, the expression of VAChT has been correlated with the severity of the dementia and has been considered as a significant diagnostic target for AD. To this end numerous radioligands based on the vesamicol scaffold have been developed for imaging the VAChT using positron emission tomography (PET). Among the various radioligands only a small number have been evaluated in vivo in non-human primate and human. Despite promising in vitro, ex vivo and first in vivo studies, most of them are unsuitable for clinical use in humans due to poor selectivity over σ receptors, low extraction from the blood, slow brain kinetics or fast metabolism. To date (-)-[11C]OMV (1), (-)-[11C]MABV (2), (-)-[18F]-FEOBV (6), (-)-trans-2-hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidine) tetralin (8) and [18F]FBMV (12) are promising radioligands for the VAChT, though further validation is required to confirm their clinical usefulness.
Export Options
About this article
Cite this article as:
Giboureau Nicolas, Mat Som Ian, Boucher-Arnold Aurelie, Guilloteau Denis and Kassiou Michael, PET Radioligands for the Vesicular Acetylcholine Transporter (VAChT), Current Topics in Medicinal Chemistry 2010; 10 (15) . https://dx.doi.org/10.2174/156802610793176846
DOI https://dx.doi.org/10.2174/156802610793176846 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Complex Actions of Statins in Brain and their Relevance for Alzheimer`s Disease Treatment: An Analytical Review
Current Alzheimer Research Meet the Editorial Board:
Letters in Drug Design & Discovery O-GlcNAc Modification and the Tauopathies: Insights from Chemical Biology
Current Alzheimer Research Molecular Chaperones as Rational Drug Targets for Parkinsons Disease Therapeutics
CNS & Neurological Disorders - Drug Targets Decoding the Inter-Relationship between Sleep Disorders and Alzheimer’s Disease Pathogenesis
CNS & Neurological Disorders - Drug Targets On the Analysis of Fingertip Photoplethysmogram Signals
Current Cardiology Reviews Preface
Current Enzyme Inhibition The Contribution of Proteinase-Activated Receptors to Intracellular Signaling, Transcellular Transport and Autophagy in Alzheimer´s Disease
Current Alzheimer Research Energy Expenditure of Hunter-Gatherers: When Statistics Turns to be Unreliable
Endocrine, Metabolic & Immune Disorders - Drug Targets Editorial - Progress of Current Alzheimer Research
Current Alzheimer Research Microwave Assisted One-pot Three Component Synthesis of Novel 2-(5- Aryloxymethyl-1,3,4-thiadiazolo)-3-aryl-4-thiazolidinones
Letters in Organic Chemistry Flavonoids Health Benefits and Their Molecular Mechanism
Mini-Reviews in Medicinal Chemistry Scientific Basis for the Use of Indian Ayurvedic Medicinal Plants in the Treatment of Neurodegenerative Disorders: 1. Ashwagandha
Central Nervous System Agents in Medicinal Chemistry New Trends in the Design of Drugs Against Alzheimers Disease
Current Medicinal Chemistry Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Recent Patents on CNS Drug Discovery (Discontinued) Transcranial Magnetic Stimulation on Rodent Models
CNS & Neurological Disorders - Drug Targets Novel Therapies for Schizophrenia: Understanding the Glutamatergic Synapse and Potential Targets for Altering N-methyl-D-aspartate Neurotransmission
Recent Patents on CNS Drug Discovery (Discontinued) Development of Computer-AidedCognitive Training Program for Elderly and Its Effectivenessthrougha 6 Months Group Intervention Study
Current Alzheimer Research Coarse Classification to Region-Scalable Refining for White Matter Lesions Segmentation in Multi-Channel MRI
CNS & Neurological Disorders - Drug Targets Safety and Efficacy of Duloxetine in the Treatment of Diabetic Peripheral Neuropathic Pain in Older Patients
Current Drug Safety