Novel indanone derivatives as potential imaging probes for β-amyloid plaques in the brain.
Molecular imaging probes to detect senile plaques (SPs) might help the early diagnosis of Alzheimer's disease (AD). In this study, a novel series of indanone derivatives were synthesized and characterized. In in vitro binding studies, compound 2e exhibited a K(i) value of 16 nM with a human AD brain homogenate. Although they displayed relatively low affinities for 2i and 2j--with K(i) values of 99 and 237 nM, respectively--the SPs in AD brain sections were positively stained by 2j. A method for in situ micro-autoradiography of AD brain was developed in this study and showed clear labeling of SPs by [(125)I]2i and [(125)I]2j. Both [(125)I]2i and [(125)I]2j had suitable lipophilicities and displayed high initial uptake and rapid clearance from the mouse brains. Furthermore, [(125)I]2i and [(125)I]2j were more stable in human brain homogenates than in mouse brain homogenates. These data suggest that such indanone derivatives might represent potential amyloid imaging agents for the detection of SPs in AD.
CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Room 729, Huangshan Road, Hefei, Anhui, 230027, PR China.
Jin-Ping
JP
Qiao
Chang-Sheng
CS
Gan
Chen-Wei
CW
Wang
Jin-Fang
JF
Ge
Dou-Dou
DD
Nan
Jian
J
Pan
Jiang-Ning
JN
Zhou
D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000473:pathology; D006801:Humans; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D058225:Plaque, Amyloid / Q000175:diagnosis* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D007189:Indans; D015335:Molecular Probes; D019275:Radiopharmaceuticals; C013352:indacrinone