Novel anilinophthalimide derivatives as potential probes for beta-amyloid plaque in the brain.
A group of novel 4,5-dianilinophthalimide derivatives has been synthesized in this study for potential use as beta-amyloid (Abeta) plaque probes. Staining of hippocampus tissue sections from Alzheimer's disease (AD) brain with the representative compound 9 indicated selective labeling of it to Abeta plaques. The binding affinity of radioiodinated [(125)I]9 for AD brain homogenates was 0.21 nM (K(d)), and of other derivatives ranged from 0.9 to 19.7 nM, except for N-methyl-4,5-dianilinophthalimide (K(i)>1000 nM). [(125)I]9 possessed the optimal lipophilicity with LogP value of 2.16, and its in vivo biodistribution in normal mice exhibited excellent initial brain uptake (5.16% ID/g at 2 min after injection) and a fast washout rate (0.56% ID/g at 60 min). The encouraging results suggest that this novel derivative of [(123)I]9 may have potential as an in vivo SPECT probe for detecting amyloid plaques in the brain.
Duan
Xin-Hong
XH
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, PR China.
Qiao
Jin-Ping
JP
Yang
Yang
Y
Cui
Meng-Chao
MC
Zhou
Jiang-Ning
JN
Liu
Bo-Li
BL
D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D010797:Phthalimides / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D010797:Phthalimides; C037431:phthalimide