Development of alkoxy styrylchromone derivatives for imaging of cerebral amyloid-β plaques with SPECT. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Fuchigami, Takeshi; Ogawa, Ayaka; Yamashita, Yuki; Haratake, Mamoru; Watanabe, Hiroyuki; Ono, Masahiro; Kawasaki, Masao; Yoshida, Sakura; Nakayama, Morio
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3363
• Page End: 3367
• Publication Date: 2015-08-15
• Subjects: Alzheimer's disease -- Amyloid-β plaque -- Styrylchromone -- Single photon emission computed tomography (SPECT); Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.048
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: We report here radioiodinated alkoxy styrylchromone derivatives as new SPECT imaging probes for β -amyloid plaques. 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 (A β ) plaques. Among the derivatives, the methoxy derivative14 and the dimethoxy derivative15 displayed relatively high affinity for the A β (1–42) aggregates with K i values of 22 and 46 nM, respectively. Fluorescent imaging demonstrated that14 and15 clearly labeled thioflavin-S positive A β 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 derivative15 may be a potential scaffold for the development of in vivo imaging probes targeting A β plaques in the brain. In particular, further structural modifications are required to improve the compounds binding affinity for A β .