α-Synuclein Radiotracer Development & In Vivo Imaging


α-Symptoms and pathological markers of α-synucleinopathies such as idiopathic Parkinson’s disease, dementia with Lewy bodies, and multiple systems atrophy are similar. α-synucleinopathies are characterized by selective neurodegeneration and Lewy pathology. No imaging biomarker could be used to make a definite early diagnosis of α-synucleinopathies. Although dopaminergic deficits detected with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers can aid clinical diagnosis by confirming the presence of dopaminergic neurodegeneration, dopaminergic imaging cannot visualize the preceding disease process or distinguish α-synucleinopathies from tauopathies with dopaminergic neurodegeneration, especially in the early stages of disease when the clinical presentation is unclear. Because aggregation of α-synuclein (αSyn) and Lewy disease is an early driver of α-synucleinopathies pathogenesis, it might be a viable imaging biomarker in α-synucleinopathies. 

Several antibodies and small molecule drugs that target aggregated αSyn were also being developed for treatment. However, there is no way to know if or how much they reduce aggregated αSyn levels in the brain. There was a definite unmet diagnostic and therapeutic medical need. Because of the inadequate binding qualities &/or physicochemical features of existing radiotracers, aggregated αSyn & Lewy pathologies inclusion bodies cannot be evaluated ante-mortem using SPECT/PET imaging. 

For a study, researchers sought to highlight the suitability of aggregated Syn as an imaging biomarker in α-synucleinopathies, current limitations, and lessons learned from αSyn radiotracer development, and finally propose antibody-based ligands for imaging αSyn aggregates as a complementary tool rather than a replacement for small molecule ligands.

Reference: movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28984



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