Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography

A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and evaluated as PET probes for early detection of A beta plaques. Molecular docking revealed that all of the flexible benzyloxybenzenes inserted themselves into the hydrophobic Va118_Phe20 cleft on the flat spine of the A beta fiber, in a manner similar to that of IMPY molecule. The most potent probe, [F-18]9a, exhibited a combination of high binding affinity to A beta 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). [F-18]9a clearly labeled A beta plaques in in vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex vivo autoradiography further demonstrated that [F-18]9a did penetrate the intact BBB and specifically bind to A beta plaques in vivo. Overall, [F-18]9a may be a potential PET probe for imaging A beta plaques in AD brains. (C) 2015 Elsevier Masson SAS. All rights reserved.