Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-ß imaging in Alzheimer's disease.

ABSTRACT

Non-invasive detection for amyloid-ß peptide (Aß) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aß 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aß plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aß deposition in AD brain.