Synthesis and biological evaluation of (E)-3-styrylpyridine derivatives as amyloid imaging agents for Alzheimer's disease.
A new series of (E)-3-styrylpyridine derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and examined. When in vitro binding studies using AD brain homogenates were carried out with a series of styrylpyridine derivatives, (E)-2-Bromo-5-(4-dimethylaminostyryl)pyridine (7) with a dimethylamino group showed the highest binding affinity. Compound 7 intensely stained neuritic and diffused plaques and cerebrovascular amyloids on postmortem AD brain sections. (E)-2-Iodo-5-(4-dimethylaminostyryl)pyridine, the iodo derivative of compound 7, also stained senile plaques in human AD sections. The radioiodinated ligand [125I] was successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives using hydrogen peroxide as the oxidant in high yields and with high radiochemical purity. A biodistribution study in normal mice after an intravenous injection of [125I] displayed high brain uptake and fast washout. Taken together, the data suggest that the new radio tracer, [125I], may be useful as a radioiodinated imaging agent for mapping A beta plaques in the brains of patients with AD.
Ono
Masahiro
M
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan. mono@net.nagasaki-u.ac.jp
Haratake
Mamoru
M
Nakayama
Morio
M
Kaneko
Yoshikazu
Y
Kawabata
Koichi
K
Mori
Hiroshi
H
Kung
Mei-Ping
MP
Kung
Hank F
HF
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008657:Metabolic Clearance Rate; D051379:Mice; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals