A novel 18F-labeled pyridyl benzofuran derivative for imaging of β-amyloid plaques in Alzheimer's brains.
A potential probe for PET targeting β-amyloid plaques in Alzheimer's disease (AD) brain, FPYBF-1 (5-(5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N,N-dimethylpyridin-2-amine), was synthesized and evaluated. In experiments in vitro, FPYBF-1 displayed high affinity for Aβ(1-42) aggregates (K(i)=0.9 nM), and substantial labeling of β-amyloid plaques in sections of postmortem AD brains but not control brains. In experiments in vivo, [(18)F]FPYBF-1 displayed good initial uptake (5.16%ID/g at 2 min postinjection) and rapid washout from the brain (2.44%ID/g at 60 min postinjection) in normal mice, and excellent binding to β-amyloid plaques in a murine model of AD. Furthermore, the specific labeling of plaques labeling was observed in autoradiographs of autopsied AD brain sections. [(18)F]FPYBF-1 may be a useful probe for imaging β-amyloid plaques in living brain tissue.
Cheng
Yan
Y
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Ono
Masahiro
M
Kimura
Hiroyuki
H
Kagawa
Shinya
S
Nishii
Ryuichi
R
Saji
Hideo
H
D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001344:Autopsy; D001345:Autoradiography; D001572:Benzofurans / Q000737:chemistry; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry
D016229:Amyloid beta-Peptides; D001572:Benzofurans; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C105430:benzofuran