Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs), ubiquitously distributed in the human brain, are implicated in various neurophysiological processes and in the pathophysiology and/or treatment strategies of Alzheimers and Parkinsons diseases, Tourettes syndrome, epilepsy, schizophrenia, depression, and anxiety, as well as being particularly affected in tobacco dependence/withdrawal. In the past two decades, researchers have developed an extensive series of radioligands for the assessment of nAChRs in vivo through emission tomography, PET and SPECT. Several radioligands, derivatives of A-85380: 2-[18F]FA, 6-[18F]FA and 5-[123I]IA, are now being employed for the evaluation of nAChR in humans with PET and SPECT. Displaying better imaging properties than 11C-nicotine and a better toxicity profile than epibatidine analogs, they have allowed quantification of thalamic nAChR in the human brain. Nevertheless, A-85380 derivatives still exhibit slow brain kinetics and a moderate signal-to-noise ratio. Current research efforts on the part of PET/SPECT radiochemists, therefore, have focused on development of new, highly specific and highly selective nAChR radioligands with improved brain kinetics that are able to localize high-affinity nAChRs in vivo. Key examples of new PET/SPECT ligands that are derived from several different structural classes are discussed along with a review of their chemical as well as their in vitro and/or in vivo properties. In particular, new PET nAChR radioligands will be examined that either present faster brain kinetics allowing simple and reliable quantification approaches or higher binding potentials suitable for the evaluation of extrathalamic nAChR.
Keywords: Neurodegenerative Diseases, positron emission tomography (PET), Brain Receptor Density, BBB transport, PET-labeled epibatidine
Current Pharmaceutical Design
Title: The Quest for Eldorado: Development of Radioligands for In Vivo Imaging of Nicotinic Acetylcholine Receptors in Human Brain
Volume: 12 Issue: 30
Author(s): Andrew G. Horti and Victor L. Villemagne
Affiliation:
Keywords: Neurodegenerative Diseases, positron emission tomography (PET), Brain Receptor Density, BBB transport, PET-labeled epibatidine
Abstract: Neuronal nicotinic acetylcholine receptors (nAChRs), ubiquitously distributed in the human brain, are implicated in various neurophysiological processes and in the pathophysiology and/or treatment strategies of Alzheimers and Parkinsons diseases, Tourettes syndrome, epilepsy, schizophrenia, depression, and anxiety, as well as being particularly affected in tobacco dependence/withdrawal. In the past two decades, researchers have developed an extensive series of radioligands for the assessment of nAChRs in vivo through emission tomography, PET and SPECT. Several radioligands, derivatives of A-85380: 2-[18F]FA, 6-[18F]FA and 5-[123I]IA, are now being employed for the evaluation of nAChR in humans with PET and SPECT. Displaying better imaging properties than 11C-nicotine and a better toxicity profile than epibatidine analogs, they have allowed quantification of thalamic nAChR in the human brain. Nevertheless, A-85380 derivatives still exhibit slow brain kinetics and a moderate signal-to-noise ratio. Current research efforts on the part of PET/SPECT radiochemists, therefore, have focused on development of new, highly specific and highly selective nAChR radioligands with improved brain kinetics that are able to localize high-affinity nAChRs in vivo. Key examples of new PET/SPECT ligands that are derived from several different structural classes are discussed along with a review of their chemical as well as their in vitro and/or in vivo properties. In particular, new PET nAChR radioligands will be examined that either present faster brain kinetics allowing simple and reliable quantification approaches or higher binding potentials suitable for the evaluation of extrathalamic nAChR.
Export Options
About this article
Cite this article as:
Horti Andrew G. and Villemagne Victor L., The Quest for Eldorado: Development of Radioligands for In Vivo Imaging of Nicotinic Acetylcholine Receptors in Human Brain, Current Pharmaceutical Design 2006; 12 (30) . https://dx.doi.org/10.2174/138161206778559605
DOI https://dx.doi.org/10.2174/138161206778559605 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Therapeutic Potential of Metabotropic GABA (GABAB) Receptors and their Effector Ion Channels
Central Nervous System Agents in Medicinal Chemistry Recent Progress in Biological Activities of Indole and Indole Alkaloids
Mini-Reviews in Medicinal Chemistry Inhalational Anesthetic Sevoflurane Rescues Retina Function in Alzheimer’s Disease Transgenic Drosophila
Current Alzheimer Research Neurogenic Drugs and Compounds to Treat CNS Diseases and Disorders
Central Nervous System Agents in Medicinal Chemistry Emerging Evidence for the Role of Neurotransmitters in the Modulation of T Cell Responses to Cognate Ligands
Central Nervous System Agents in Medicinal Chemistry Receptor to Glutamate NMDA-Type: The Functional Diversity of the NR1 Isoforms and Pharmacological Properties
Current Pharmaceutical Design The Design of Multi-target Drugs to Treat Cardiovascular Diseases: Two (or more) Birds on One Stone
Current Topics in Medicinal Chemistry Classification of Normal and Epileptic EEG Signals Using Adaptive Neuro-Fuzzy Network Based on Time Series Prediction
Neuroscience and Biomedical Engineering (Discontinued) The Potentials of Uncariae Ramulus Cum Uncis for the Treatment of Migraine: Targeting CGRP in the Trigeminovascular System
Current Neuropharmacology Modulation and Absorption of Xenobiotics: The Synergistic Role of CYP450 and P-gp Activities in Cancer and Neurodegenerative Disorders
Current Drug Metabolism From Axonal Transport to Mitochondrial Trafficking: What Can We Learn from Manganese-Enhanced MRI Studies in Mouse Models of Alzheimers Disease?
Current Medical Imaging Cognitive Impairment and Mossy Fiber Sprouting in a Rat Model of Drug-resistant Epilepsy Induced by Lithium-pilocarpine
Current Neurovascular Research The Neurotachykinin NK1 Receptor – A Novel Target for Diagnostics and Therapy
Current Molecular Imaging (Discontinued) Nanoparticulate Drug Delivery in Pregnancy: Placental Passage and Fetal Exposure
Current Pharmaceutical Biotechnology Hallucinations Associated with Topiramate Therapy: A Case Report and Review of the Literature
Current Drug Safety Substituted Aminobenzothiazole Derivatives of Tacrine: Synthesis and Study on Learning and Memory Impairment in Scopolamine-Induced Model of Amnesia in Rat
Mini-Reviews in Medicinal Chemistry Cerebroprotective Functions of HO-2
Current Pharmaceutical Design Zinc-Permeable Ion Channels: Effects on Intracellular Zinc Dynamics and Potential Physiological/Pathophysiological Significance
Current Medicinal Chemistry Principles and Applications of Diffuse Optical Imaging for the Brain
Current Medical Imaging Recent Inventions on Receptor Tyrosine Kinase RET Modulation
Recent Patents on Biotechnology