Lipophilic Analogs of Thioflavin S as Novel Amyloid-Imaging Agents

Authors: Wu, Chunying; Cai, Lisheng; Wei, Jingjun; Pike, Victor W.; Wang, Yanming

Source: Current Alzheimer Research, Volume 3, Number 3, July 2006 , pp. 259-266(8)

Publisher: Bentham Science Publishers

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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

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156720506777632862

Affiliations: 1: College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.

Publication date: 2006-07-01

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Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

Lipophilic Analogs of Thioflavin S as Novel Amyloid-Imaging Agents

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