Rhodanine and thiohydantoin derivatives for detecting tau pathology in Alzheimer's brains.
A novel series of rhodanin (RH) and thiohydantoin (TH) derivatives were designed and synthesized for detecting tau pathology in the brains of patients with Alzheimer's disease (AD). In experiments in vitro using tau and β-amyloid (Aβ) aggregates, the TH derivative, TH2, showed high specific binding to tau aggregates. In hippocampal sections obtained from AD patients, TH2 intensely stained neurofibrillary tangles. In experiments using normal mice, [(125)I]TH2 showed good uptake (1.54%ID/g, 2 min postinjection) into and a rapid washout (0.25%ID/g, 60 min postinjection) from the brain. [(123)I]TH2 should be further investigated as a potential imaging agent for detecting tau pathology.
Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. ono@pharm.kyoto-u.ac.jp
Masahiro
M
Ono
Shun
S
Hayashi
Kenji
K
Matsumura
Hiroyuki
H
Kimura
Yoko
Y
Okamoto
Masafumi
M
Ihara
Ryosuke
R
Takahashi
Hiroshi
H
Mori
Hideo
H
Saji
D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D000818:Animals; D001345:Autoradiography / Q000379:methods; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D016874:Neurofibrillary Tangles; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D012236:Rhodanine / Q000138:chemical synthesis* / Q000737:chemistry; D024801:Tauopathies / Q000000981:diagnostic imaging*; D013844:Thiazoles / Q000037:antagonists & inhibitors; D013867:Thiohydantoins / Q000138:chemical synthesis* / Q000737:chemistry; D014018:Tissue Distribution
D052160:Benzothiazoles; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D013844:Thiazoles; D013867:Thiohydantoins; C009462:thioflavin T; D012236:Rhodanine