Multidentate 18F-Polypegylated Styrylpyridines As Imaging Agents for Aβ Plaques in Cerebral Amyloid Angiopathy (CAA)
- 19 October 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 54 (23), 8085-8098
- https://doi.org/10.1021/jm2009106
Abstract
β-Amyloid plaques (Aβ plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the Aβ plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of 18F styrylpyridine derivatives with high molecular weights for selectively targeting Aβ plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a–c, display high binding affinities and specificity to Aβ plaques (Ki = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [18F]8a shows labeling of β-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [18F]8a may be a useful PET imaging agent for selectively detecting Aβ plaques associated with cerebral vessels in the living human brain.Keywords
This publication has 47 references indexed in Scilit:
- Cerebral Microbleeds in the ElderlyStroke, 2010
- High-definition characterization of cerebral β-amyloid angiopathy in Alzheimer's diseaseHuman Pathology, 2010
- Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's diseaseBrain, 2010
- Spatial relation between microbleeds and amyloid deposits in amyloid angiopathyAnnals of Neurology, 2010
- PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptidesEuropean Journal of Nuclear Medicine and Molecular Imaging, 2010
- In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18F-AV-45 (Flobetapir F 18)Journal of Nuclear Medicine, 2010
- 18F Stilbenes and Styrylpyridines for PET Imaging of Aβ Plaques in Alzheimer’s Disease: A MiniperspectiveJournal of Medicinal Chemistry, 2009
- Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the BrainJournal of Nuclear Medicine, 2009
- Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer diseaseAlzheimer's Research & Therapy, 2009
- Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's diseaseBrain, 2008