Synthesis and characterization of novel phenylindoles as potential probes for imaging of β-amyloid plaques in the brain.
We synthesized a novel series of phenylindole (PI) derivatives and evaluated their biological activities as probes for imaging Aβ plaques in vivo. The affinity for Aβ plaques was assessed by an in vitro-binding assay using pre-formed synthetic Aβ aggregates. 2-phenyl-1H-indole (2-PI) derivatives showed high affinity for Aβ42 aggregates with K(i) values ranging from 4 to 32 nM. 2-PI derivatives clearly stained Aβ plaques in an animal model of AD. In biodistribution experiments using normal mice, 2-PI derivatives displayed sufficient uptake for imaging, ranging from 1.1% to 2.6% ID/g. Although additional modifications are necessary to improve uptake by and clearance from the brain, 2-PI derivatives may be useful as a backbone structure to develop novel Aβ imaging agents.
Watanabe
Hiroyuki
H
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Ono
Masahiro
M
Haratake
Mamoru
M
Kobashi
Nobuya
N
Saji
Hideo
H
Nakayama
Morio
M
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D007211:Indoles; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C075222:amyloid beta-protein (1-42)