Synthesis and biological evaluation of radioiodinated 2,5-diphenyl-1,3,4-oxadiazoles for detecting beta-amyloid plaques in the brain.
This paper describes the synthesis and biological evaluation of a new series of 2,5-diphenyl-1,3,4-oxadiazole (1,3,4-DPOD) derivatives for detecting beta-amyloid plaques in Alzheimer's brains. The affinity for beta-amyloid plaques was assessed by an in vitro binding assay using pre-formed synthetic Abeta42 aggregates. The new series of 1,3,4-DPOD derivatives showed affinity for Abeta42 aggregates with K(i) values ranging from 20 to 349 nM. The 1,3,4-DPOD derivatives clearly stained beta-amyloid plaques in an animal model of Alzheimer's disease, reflecting the affinity for Abeta42 aggregates in vitro. Compared to 3,5-diphenyl-1,2,4-oxadiazole (1,2,4-DPOD) derivatives, they displayed good penetration of and fast washout from the brain in biodistribution experiments using normal mice. The novel radioiodinated 1,3,4-DPOD derivatives may be useful probes for detecting beta-amyloid plaques in the Alzheimer's brain.
Watanabe
Hiroyuki
H
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Ono
Masahiro
M
Ikeoka
Ryoichi
R
Haratake
Mamoru
M
Saji
Hideo
H
Nakayama
Morio
M
D000544:Alzheimer Disease / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology*; D007457:Iodine Radioisotopes / Q000737:chemistry; D051379:Mice; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D058225:Plaque, Amyloid / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D010069:Oxadiazoles; D019275:Radiopharmaceuticals