Heterocyclic molecules for biomedical imaging and therapeutic applications

Abstract

Probes which target diffuse and fibrillar forms of amyloid beta (Aβ) are described. These probes demonstrate high initial brain penetration and facile clearance from non-targeted regions. The agents can be used to image amyloid quantitatively for monitoring efficacy of Aβ-modifying therapeutics and assist in premortem diagnosis of Alzheimer's disease (AD). Disclosed probes can bind Aβ aggregates of preformed Aβ1-42 fibrils in vitro and can be used to image fibrillar and diffuse plaques ex vivo in brain sections. Disclosed probes can be used to determine Aβ burden in early stages of AD. These probes can be used for multimodality imaging of Aβ. F-AI-187 (1 μM) can detect Aβ plaques in brain sections of APP/PS1 mice. F-AI-187 (10 μM) can detect Aβ plaques in the frontal lobe in a brain section of a patient with confirmed AD. Some probes can be used for fluorescence imaging of plaque.

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