[Molecular imaging of beta-amyloid plaques in the brain]

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia, cognitive impairment, and memory loss. Postmortem brains of AD patients reveal neuropathological features; the presence of beta-amyloid plaques and neurofibrillary tangles, which contain beta-amyloid peptides (Abeta) and highly phosphorylated tau proteins. Increases in the concentration of Abeta in the course of the disease lead to gradual increase in the load of beta-amyloid plaques, which is thought to be an initial neuropathological change in AD brains. Thus, the development of radiotracers for in vivo imaging beta-amyloid plaques in the aging human brain is an important and active area of molecular imaging. When used in combination with positron emission tomography (PET) or single photon emission computed tomography (SPECT), amyloid imaging agents could serve as surrogate markers in early diagnosis and neuropathogenesis studies of AD. Furthermore, quantitative evaluation of beta-amyloid plaques in the brain could allow facilitate the evaluation of the efficacy of anti-amyloid therapies that are currently being investigated. A number of groups have worked to develop radiolabeled amyloid imaging agents, and clinical trials in AD patients have been reported with several agents including [18F]FDDNP, [11C]PIB, [11C]SB-13 and [123I]IMPY, indicating that detecting beta-amyloid plaques in the living human brain with amyloid imaging agents is potentially feasible. More recently, we have reported additional promising compounds such as flavone or chalcone derivatives. The combination of relatively high binding affinity to Abeta and high brain uptake and good clearance in mice of these flavonoid derivatives provides a series of potential amyloid imaging agents for PET and SPECT. In this manuscript, recent progress in amyloid imaging studies is reviewed with the development of amyloid imaging agents.