| First Author | Xiang J | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 16 | Pages | 3350-3367.e19 |
| PubMed ID | 37421950 | Mgi Jnum | J:339320 |
| Mgi Id | MGI:7518073 | Doi | 10.1016/j.cell.2023.06.004 |
| Citation | Xiang J, et al. (2023) Development of an alpha-synuclein positron emission tomography tracer for imaging synucleinopathies. Cell 186(16):3350-3367.e19 |
| abstractText | Synucleinopathies are characterized by the accumulation of alpha-synuclein (alpha-Syn) aggregates in the brain. Positron emission tomography (PET) imaging of synucleinopathies requires radiopharmaceuticals that selectively bind alpha-Syn deposits. We report the identification of a brain permeable and rapid washout PET tracer [(18)F]-F0502B, which shows high binding affinity for alpha-Syn, but not for Abeta or Tau fibrils, and preferential binding to alpha-Syn aggregates in the brain sections. Employing several cycles of counter screenings with in vitro fibrils, intraneuronal aggregates, and neurodegenerative disease brain sections from several mice models and human subjects, [(18)F]-F0502B images alpha-Syn deposits in the brains of mouse and non-human primate PD models. We further determined the atomic structure of the alpha-Syn fibril-F0502B complex by cryo-EM and revealed parallel diagonal stacking of F0502B on the fibril surface through an intense noncovalent bonding network via inter-ligand interactions. Therefore, [(18)F]-F0502B is a promising lead compound for imaging aggregated alpha-Syn in synucleinopathies. |
