Metal complexes for the visualisation of amyloid peptides

Abstract

Amyloid forms of many different proteins have been long identified as relevant biomarkers in important pathologies with high societal impact, including Aβ in Alzheimer's disease, amylin in type 2 diabetes, α-synuclein in Parkinson's disease, etc. With over eighty novel complexes reported in the last six years, metal-based agents designed for the detection of such amyloid fibrils represent a rapidly growing field in molecular imaging. While the majority of these examples are radiocomplexes for nuclear imaging and focus on the detection of Aβ in Alzheimer's disease, there is increasing interest in other peptides and pathologies, and few studies are also directed at magnetic resonance imaging probes. In this review, we survey the recent literature according to the chemical nature of the amyloid recognition moieties, most of which are derived from a few basic structures, including benzothiazole, benzofuran or stilbene. Relationships between chemical structure and amyloid binding properties and biodistribution, in particular brain delivery and brain clearance, are outlined in order to help further work in this emerging area of research.