title: Homoisoflavonoids as potential imaging agents for β-amyloid plaques in Alzheimer's disease.
abstract: A series of homoisoflavonoids [(E)-3-benzylidenechroman-4-ones, 3a-l] as novel potential diagnostic imaging agents targeting β-amyloid (Aβ) plaques in Alzheimer's disease (AD) were synthesized and evaluated. In vitro binding studies using Aβ₁₋₄₀ aggregates with [(125)I]IMPY as the reference ligand showed that these compounds demonstrated high to low binding affinities at the K(i) values ranged from 9.10 to 432.03 nM, depending on the substitution of the phenyl ring. Fluorescent staining in vitro indicated that one compound with a N,N-dimethylamino group intensely stained Aβ plaques within brain sections of postmortem AD patients. Biodistribution studies in normal mice after i.v. injection of the radioiodinated homoisoflavonoid displayed good initial brain uptake (2.61% ID/g at 2 min postinjection) and rapid clearance from the brain (0.18% ID/g at 60 min), which is desirable for amyloid imaging agents. The results strongly suggest that these derivatives are worthy of further study and may be useful amyloid imaging agents for early detection of amyloid plaques in the brain of AD.
authors.affiliation: Engineering Research Center of Bio-process of Ministry of Education, Hefei University of Technology, Hefei, Anhui 230009, PR China. Electronic address: gancs7894@163.com.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Gan
authors.affiliation: Engineering Research Center of Bio-process of Ministry of Education, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Dou-Dou
authors.initials: DD
authors.lastname: Nan
authors.affiliation: Engineering Research Center of Bio-process of Ministry of Education, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Yin
authors.affiliation: Engineering Research Center of Bio-process of Ministry of Education, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hu
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D000818:Animals; D005419:Flavonoids / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008813:Mice, Inbred ICR; D058225:Plaque, Amyloid / Q000175:diagnosis*; D011869:Radioligand Assay; D014018:Tissue Distribution
chemical_list: D005419:Flavonoids; D007457:Iodine Radioisotopes
keywords: Alzheimer's disease; Amyloid; Binding assay; Homoisoflavonoid; Imaging agent