1. Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography.
- Author
-
Yang, Yanping, Fu, Hualong, Cui, Mengchao, Peng, Cheng, Liang, Zhigang, Dai, Jiapei, Zhang, Zhiyong, Lin, Chunping, and Liu, Boli
- Subjects
- *
BENZENE synthesis , *AMYLOID plaque , *POSITRON emission tomography , *MOLECULAR docking , *AUTORADIOGRAPHY , *ALZHEIMER'S patients - Abstract
A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of A β plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Val18_Phe20 cleft on the flat spine of the A β fiber, in a manner similar to that of IMPY molecule. The most potent probe, [ 18 F] 9a , exhibited a combination of high binding affinity to A β aggregates ( K i = 21.0 ± 4.9 nM), high initial brain uptake (9.14% ID/g at 2 min), fast clearance from normal brain tissue (1.79% ID/g at 60 min), and satisfactory in vivo biostability in the brain (95% of intact form at 2 min). [ 18 F] 9a clearly labeled A β plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [ 18 F] 9a did penetrate the intact BBB and specifically bind to A β plaques in vivo . Overall, [ 18 F] 9a may be a potential PET probe for imaging A β plaques in AD brains. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF