Fluoro-pegylated chalcones as positron emission tomography probes for in vivo imaging of beta-amyloid plaques in Alzheimer's disease.
This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of beta-amyloid (Abeta) plaques in patients with Alzheimer's disease (AD). FPEG chalcone derivatives were prepared by the aldol condensation reaction. In binding experiments conducted in vitro using Abeta(1-42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher Ki values (20-50 nM) than those having a monomethylamino or a primary amine group. When the biodistribution of 11C-labeled FPEG chalcone derivatives having a dimethyamino group was examined in normal mice, all four derivatives were found to display sufficient uptake for imaging Abeta plaques in the brain. 18F-labeled 7c also showed good uptake by and clearance from the brain, although a slight difference between the 11C and 18F tracers was observed. When the labeling of Abeta plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled Abeta plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting Abeta plaques in the brain of patients with AD.
Ono
Masahiro
M
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ono@pharm.kyoto-u.ac.jp
Watanabe
Rumi
R
Kawashima
Hidekazu
H
Cheng
Yan
Y
Kimura
Hiroyuki
H
Watanabe
Hiroyuki
H
Haratake
Mamoru
M
Saji
Hideo
H
Nakayama
Morio
M
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D015195:Drug Design; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D054879:Halogenation; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D047188:Chalcones; D005462:Fluorine Radioisotopes; D011092:Polyethylene Glycols