18F-labeled flavones for in vivo imaging of beta-amyloid plaques in Alzheimer's brains.
In vivo imaging of beta-amyloid (Abeta) aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. The purpose of this study was to develop novel (18)F-labeled amyloid-imaging probes based on flavones as a core structure. Fluoropegylated (FPEG) flavone derivatives were designed and synthesized. The affinity of the derivatives for Abeta aggregates varied from 5 to 321nM. In brain sections of AD model mice, FPEG flavones with the dimethylamino group intensely stained beta-amyloid plaques. In biodistrubution experiments using normal mice, they displayed high uptake in the brain ranging from 2.9 to 4.2%ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (1.3-2.0%ID/g at 30 min), which is highly desirable for beta-amyloid imaging agents. FPEG flavones may be potential PET imaging agents for beta-amyloid plaques in Alzheimer's brains.
Ono
Masahiro
M
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Watanabe
Rumi
R
Kawashima
Hidekazu
H
Kawai
Tomoki
T
Watanabe
Hiroyuki
H
Haratake
Mamoru
M
Saji
Hideo
H
Nakayama
Morio
M
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D051379:Mice; D023421:Models, Animal; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D047309:Flavones; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols