Tracer development for PET imaging of proteinopathies

Abstract

This review outlines small molecule radiotracers developed for positron emission tomography (PET) imaging of proteinopathies, neurodegenerative diseases characterised by accumulation of malformed proteins, over the last two decades with the focus on radioligands that have progressed to clinical studies. Introduction provides a short summary of proteinopathy targets used for PET imaging, including vastly studied proteins Aβ and tau and emerging α-synuclein. In the main section, clinically relevant Aβ and tau radioligand classes and their properties are discussed, including an overview of lead compounds and radioligand candidates studied as α-synuclein imaging agents in the early discovery and preclinical development phase. Lastly, the specific challenges and future directions in proteinopathy radioligand development are summarized.