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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]

Alzheimer's disease (AD) is a debilitating neurodegenerative dementia that involves substantial neuronal loss. Extracellular deposition of neurotoxic β -amyloid (A β ) plaques in the brain has been recognized as the central histological characteristic of AD. In the past decade, precise detection of the A β plaques at preclinical AD with positron emission tomography (PET) or single photon emission computed tomography (SPECT) has achieved continued development. A big category of A β imaging agents was benzoheterocycles which derived from Thioflavin-T (ThT), a traditional amyloid binding dye. This review summarizes the past and current status of radioactive benzoheterocycles designed to selectively bind to A β plaques. Separate sections discuss the chemical synthesis, in vitro and in vivo investigations of radiolabeled benzothiazole, benzoxazole, benzofuran, benzothiophene, indole, imidazopyridine and quinoxaline analogs to act as PET/SPECT candidates for imaging A β plaques. [ABSTRACT FROM AUTHOR]