Abstract
The development of radioligands to image β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (PET) or single photon emission computed tomography (SPECT), amyloid-imaging tracers could facilitate the evaluation of the efficacy of anti-amyloid therapies currently under intense development by many major pharmaceutical companies throughout the world. Amyloid-imaging agents could also serve as surrogate markers in early diagnosis and neuropathogenesis studies of Alzheimers disease and other aging-related neurodegenerative disorders. In this review article, the design and biological evaluation of amyloid-imaging agents are discussed. The structures of these agents vary from large proteins and peptides such as radiolabeled Aβ peptides and monoclonal antibodies to small molecules derived from Congo red, Chrysamine-G, thioflavin-T, and Acridine Orange. In vitro studies indicate that amyloid plaques contain multiple binding sites that can accommodate structurally diverse compounds, providing flexibility for radiopharmaceutical design of amyloid imaging agents. Compared to large biomolecules, small molecule radiotracers are often readily accessible through chemical synthesis and can display superior brain permeability. Several small molecule amyloid-imaging radioligands display high binding affinities to Aβ and sufficient brain penetration for imaging studies. Recent studies demonstrate the feasibility of imaging amyloid plaques in vivo in human subjects with PET. Imaging NFTs, separately or in concert with Ab plaques, is not as far advanced as imaging Aβ plaques and remains to be fully characterized and demonstrated.
Keywords: amyloid, neurofibrillary tangles, imaging, pet, spect, alzheimer disease
Current Pharmaceutical Design
Title: Imaging β-Amyloid Plaques and Neurofibrillary Tangles in the Aging Human Brain
Volume: 10 Issue: 13
Author(s): C. A. Mathis, Y. Wang and W. E. Klunk
Affiliation:
Keywords: amyloid, neurofibrillary tangles, imaging, pet, spect, alzheimer disease
Abstract: The development of radioligands to image β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (PET) or single photon emission computed tomography (SPECT), amyloid-imaging tracers could facilitate the evaluation of the efficacy of anti-amyloid therapies currently under intense development by many major pharmaceutical companies throughout the world. Amyloid-imaging agents could also serve as surrogate markers in early diagnosis and neuropathogenesis studies of Alzheimers disease and other aging-related neurodegenerative disorders. In this review article, the design and biological evaluation of amyloid-imaging agents are discussed. The structures of these agents vary from large proteins and peptides such as radiolabeled Aβ peptides and monoclonal antibodies to small molecules derived from Congo red, Chrysamine-G, thioflavin-T, and Acridine Orange. In vitro studies indicate that amyloid plaques contain multiple binding sites that can accommodate structurally diverse compounds, providing flexibility for radiopharmaceutical design of amyloid imaging agents. Compared to large biomolecules, small molecule radiotracers are often readily accessible through chemical synthesis and can display superior brain permeability. Several small molecule amyloid-imaging radioligands display high binding affinities to Aβ and sufficient brain penetration for imaging studies. Recent studies demonstrate the feasibility of imaging amyloid plaques in vivo in human subjects with PET. Imaging NFTs, separately or in concert with Ab plaques, is not as far advanced as imaging Aβ plaques and remains to be fully characterized and demonstrated.
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Cite this article as:
Mathis A. C., Wang Y. and Klunk E. W., Imaging β-Amyloid Plaques and Neurofibrillary Tangles in the Aging Human Brain, Current Pharmaceutical Design 2004; 10 (13) . https://dx.doi.org/10.2174/1381612043384772
DOI https://dx.doi.org/10.2174/1381612043384772 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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