title: Synthesis and biological evaluation of (E)-3-styrylpyridine derivatives as amyloid imaging agents for Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan. mono@net.nagasaki-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Mamoru
authors.initials: M
authors.lastname: Haratake
authors.forename: Morio
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Mei-Ping
authors.initials: MP
authors.lastname: Kung
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals