Development of alkoxy styrylchromone derivatives for imaging of cerebral amyloid-β plaques with SPECT

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Fuchigami, Takeshi¹  Ogawa, Ayaka¹  Yamashita, Yuki¹  Haratake, Mamoru^1,2  Watanabe, Hiroyuki³  Ono, Masahiro³  Kawasaki, Masao¹  Yoshida, Sakura¹  Nakayama, Morio¹ 

[1] Nagasaki Univ, Grad Sch Biomed Sci, Dept Hygien Chem, Nagasaki 8528521, Japan

[2] Sojo Univ, Fac Pharmaceut Sci, Kumamoto 8600082, Japan

[3] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

关键词: Alzheimer's disease;    Amyloid-beta plaque;    Styrylchromone;    Single photon emission computed tomography (SPECT);   

DOI  :  10.1016/j.bmcl.2015.05.048

来源: Elsevier

【 摘 要 】

We report here the development of radioiodinated styrylchromone derivatives with alkoxy groups as single photon emission computed tomography (SPECT) imaging probes for cerebral amyloid-beta (A beta) plaques. Among the derivatives, the methoxy derivative 14 and the dimethoxy derivative 15 displayed relatively high affinity for the A beta(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 A beta plaques in the brain sections of Tg2576 transgenic mice. In the in vivo studies, [I-125]14 and [I-125]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 [I-125]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 A beta plaques in the brain. In particular, further structural modifications are required to improve the compounds binding affinity for A beta. (C) 2015 Elsevier Ltd. All rights reserved.

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