PET tracer development for imaging α-synucleinopathies

Abstract

Abnormal α-synuclein aggregation is a key neuropathological hallmark of α-synucleinopathies, such as Parkinson's disease (PD), multiple system atrophy (MSA), and several other neurological disorders, and closely contributes to pathogenesis. The primary characteristics of α-synucleinopathies are selective targeted neurodegeneration and the accumulation of Lewy pathologies. Specifically, α-synuclein positron emission tomography (PET) radiotracers target the fibrillar forms of the protein, thus enhancing early diagnosis and the evaluation of treatment effectiveness for various α-synucleinopathies. Therefore, in vivo detection of α-synuclein aggregates using targeted radiolabeled probes would aid in drug development, early diagnosis, and ongoing disease monitoring. As such, no promising α-synuclein biomarkers suitable for clinical applications have been reported. PET is a valuable non-invasive technique for imaging drug distribution in tissues and receptor occupancy at target sites in living animals and humans. Advances in PET biomarkers have significantly enhanced our understanding of the mechanisms underlying PD. This review summarizes recent ongoing efforts in the development of selective PET tracers for α-synuclein and discusses future perspectives.

Keywords: Neurodegeneration; Parkinson’s disease; Radiotracer; α-Synuclein aggregates; α-Synucleinopathies.