New PET Tracer Allows Visualization of Synucleinopathies

Chinese Academy of Sciences

Brain imaging scans are powerful tools for diagnosing Parkinson's disease (PD) and ruling out other motor disorders. In PD, the presence of α-synuclein (α-Syn) in Lewy bodies and Lewy neurites in the brain, particularly the substantia nigra, distinguishes it from other parkinsonisms. Unfortunately, there is currently no effective α-Syn PET tracer available.

Now, a research team led by Prof. YE Keqiang from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has discovered a promising compound called F0502B for imaging α-Syn and aiding in the diagnosis of synucleinopathies.

The study was published in Cell on July 7.

The researchers found that in monkey PD models, when [18F]-labeled, F0502B specifically bound to α-Syn fibrils with high affinity, distinguishing them from Aβ and Tau fibrils.

PET imaging in monkey models showed that [18F]-F0502B specifically detected α-Syn aggregates. The levels of aggregated α-Syn may increase over time, leading to elevated PET-specific binding signals.

F0502B can act as neuroimaging radiotracer due to its certain chemical and pharmacological properties, including high permeability through the blood-brain barrier, rapid clearance from normal brain tissue and blood, and high-affinity binding and selectivity for the target.

"Our findings demonstrate that F0502B acts as a specific PET tracer by selectively binding to aggregated α-Syn," said Prof. YE, corresponding author of the study. "This could enhance our understanding of disease progression and potentially facilitate monitoring therapeutic efficacy in clinical trials."

The discovery of F0502B represents a promising lead compound for imaging α-synuclein inclusions in synucleinopathies (Image by YE Keqiang)
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