Binding of the PET Radiotracer [18F]BF227 Does not Reflect the Presence of Alpha-Synuclein Aggregates in Transgenic Mice

Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of many neurodegenerative diseases, collectively termed synucleinopathies. There is currently no pre-mortem diagnosis tool for these diseases. Although some compounds have been described as potential ligands for α-syn aggregates, no specific PET radiotracer of aggregated α-syn is currently available. Recently, [18F]BF227 has been proposed as an α-syn PET radiotracer in the absence of other specific candidates. We proposed here, for the first time, to use this radiotracer in an accelerated mouse model of synucleinopathy presenting α-syn depositions in brainstem and thalamus. Our in vivo and in vitro studies showed that [18F]BF227 does not bind to α-syn aggregates. These results highlight the fact that [18F]BF227 PET has no suitable characteristics for monitoring this experimental synucleinopathy, justifying the need to develop alternative α-syn PET radiotracers.