title: Development of alkoxy styrylchromone derivatives for imaging of cerebral amyloid-β plaques with SPECT.
abstract: We report here the development of radioiodinated styrylchromone derivatives with alkoxy groups as single photon emission computed tomography (SPECT) imaging probes for cerebral amyloid-β (Aβ) plaques. Among the derivatives, the methoxy derivative 14 and the dimethoxy derivative 15 displayed relatively high affinity for the Aβ(1-42) aggregates with K(i) values of 22 and 46 nM, respectively. Fluorescent imaging demonstrated that 14 and 15 clearly labeled thioflavin-S positive Aβ plaques in the brain sections of Tg2576 transgenic mice. In the in vivo studies, [(125)I]14 and [(125)I]15 showed high initial brain uptake expressed as the percentage of the injected dose per gram (2.25% and 2.49% ID/g at 2 min, respectively) with favorable clearance (0.12% and 0.20% ID/g at 180 min, respectively) from the brain tissue of normal mice. Furthermore, in vitro autoradiography confirmed that [(125)I]15 binds thioflavin-S positive regions in Tg2576 mouse brain sections. The derivative 15 may be a potential scaffold for the development of in vivo imaging probes targeting Aβ plaques in the brain. In particular, further structural modifications are required to improve the compounds binding affinity for Aβ.
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. Electronic address: t-fuchi@nagasaki-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fuchigami
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ogawa
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan; Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Haratake
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Sakura
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. Electronic address: morio@nagasaki-u.ac.jp.
authors.forename: Morio
authors.initials: M
authors.lastname: Nakayama
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000473:pathology*; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D058225:Plaque, Amyloid / Q000175:diagnosis*; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C552759:5-hydroxy-2-styrylchromone; D000438:Alcohols; D002867:Chromones; D013343:Styrenes; C059688:alkoxyl radical
keywords: Alzheimer’s disease; Amyloid-β plaque; Single photon emission computed tomography (SPECT); Styrylchromone