Abstract
Lipophilic analogs of thioflavin S were synthesized and radiolabeled with positron or single photon emitting radionuclides. The binding affinity for Aβ was evaluated using isolated amyloid fibrils from human brain tissue. Binding specificity was assessed using fluorescent tissue staining. In vivo brain uptake was evaluated in mice. Following synthesis, neutral analogs of thioflavin S capable of radiolabeling with 11C or 125I, were found to bind isolated human Aβ with affinities in the nanomolar range. Fluorescent tissue staining showed selective binding to Aβ deposits in vitro. Biodistribution of selected compounds displayed high brain permeability at early time points. At later points, the compounds were cleared from the normal brain, indicating low non-specific binding in vivo. These studies indicated that novel amyloid imaging probes can be developed based on thioflavin S that readily entered the brain and selectively bound to Aβ deposits and neurofibrilary tangles. Potential applications of these amyloid binding agents include facilitating drug screening in animal models and use as in vivo markers of early and definitive diagnosis of AD.
Keywords: Amyloid-β, Alzheimer's disease, Thioflavin S, PET, SPECT, Imaging
Current Alzheimer Research
Title: Lipophilic Analogs of Thioflavin S as Novel Amyloid-Imaging Agents
Volume: 3 Issue: 3
Author(s): Chunying Wu, Lisheng Cai, Jingjun Wei, Victor W. Pike and Yanming Wang
Affiliation:
Keywords: Amyloid-β, Alzheimer's disease, Thioflavin S, PET, SPECT, Imaging
Abstract: Lipophilic analogs of thioflavin S were synthesized and radiolabeled with positron or single photon emitting radionuclides. The binding affinity for Aβ was evaluated using isolated amyloid fibrils from human brain tissue. Binding specificity was assessed using fluorescent tissue staining. In vivo brain uptake was evaluated in mice. Following synthesis, neutral analogs of thioflavin S capable of radiolabeling with 11C or 125I, were found to bind isolated human Aβ with affinities in the nanomolar range. Fluorescent tissue staining showed selective binding to Aβ deposits in vitro. Biodistribution of selected compounds displayed high brain permeability at early time points. At later points, the compounds were cleared from the normal brain, indicating low non-specific binding in vivo. These studies indicated that novel amyloid imaging probes can be developed based on thioflavin S that readily entered the brain and selectively bound to Aβ deposits and neurofibrilary tangles. Potential applications of these amyloid binding agents include facilitating drug screening in animal models and use as in vivo markers of early and definitive diagnosis of AD.
Export Options
About this article
Cite this article as:
Wu Chunying, Cai Lisheng, Wei Jingjun, Pike W. Victor and Wang Yanming, Lipophilic Analogs of Thioflavin S as Novel Amyloid-Imaging Agents, Current Alzheimer Research 2006; 3 (3) . https://dx.doi.org/10.2174/156720506777632862
DOI https://dx.doi.org/10.2174/156720506777632862 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Future Targeted Disease Modifying Drugs for Alzheimer's Disease
Recent Patents on CNS Drug Discovery (Discontinued) ABC Subfamily D Proteins and Very Long Chain Fatty Acid Metabolism as Novel Targets in Adrenoleukodystrophy
Current Drug Targets Serum Cytokine Profile in Alzheimer's Disease Patients After Ingestion of an Antioxidant Beverage
CNS & Neurological Disorders - Drug Targets Human Urotensin II Promotes Hypertension and Atherosclerotic Cardiovascular Diseases
Current Medicinal Chemistry Recent Developments in Tau-Based Therapeutics for Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) The Role of Nuclear Medicine in Vascular Dementia
Vascular Disease Prevention (Discontinued) MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders
Current Genomics A<sub>3</sub> Adenosine Receptor: A Plausible Therapeutic Target for Cardio-Protection in Diabetes
Recent Patents on Cardiovascular Drug Discovery APP Transgenic Mouse Models and their Use in Drug Discovery to Evaluate Amyloid-β Lowering Therapeutics
CNS & Neurological Disorders - Drug Targets Nanotechnology Advances in Brain Tumors: The State of the Art
Recent Patents on Anti-Cancer Drug Discovery Kinetic Study on the Effects of Extremely Low Frequency Electromagnetic Field on Catalase, Cytochrome P450 and Inducible Nitric Oxide Synthase in Human HaCaT and THP-1 Cell Lines
CNS & Neurological Disorders - Drug Targets Impaired Neurovascular Coupling in the APPxPS1 Mouse Model of Alzheimer’s Disease
Current Alzheimer Research DNAJ Proteins and Protein Aggregation Diseases
Current Topics in Medicinal Chemistry Role of Physician Gender in the Quality of Care of Cardiometabolic Diseases
Current Pharmaceutical Design Hyperglycemia, Hypoglycemia and Dementia: Role of Mitochondria and Uncoupling Proteins
Current Molecular Medicine Non-Coding RNA in Brain Development and Disorder
Current Medicinal Chemistry Induced Pluripotent Stem Cell-Based Studies of Parkinson's Disease: Challenges and Promises
CNS & Neurological Disorders - Drug Targets Oxidative Stress, Antioxidants and Neurodegenerative Diseases
Current Pharmaceutical Design FDG-PET/CT for Systemic Infections
Current Molecular Imaging (Discontinued) The Panomics Approach in Neurodegenerative Disorders
Current Medicinal Chemistry