Binding of the radioligand SIL23 to α-synuclein fibrils in Parkinson disease brain tissue establishes feasibility and screening approaches for developing a Parkinson disease imaging agent

PLoS One. 2013;8(2):e55031. doi: 10.1371/journal.pone.0055031. Epub 2013 Feb 6.


Accumulation of α-synuclein (α-syn) fibrils in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson disease (PD). Ligands that bind α-syn fibrils could be utilized as imaging agents to improve the diagnosis of PD and to monitor disease progression. However, ligands for α-syn fibrils in PD brain tissue have not been previously identified and the feasibility of quantifying α-syn fibrils in brain tissue is unknown. We report the identification of the (125)I-labeled α-syn radioligand SIL23. [(125)I]SIL23 binds α-syn fibrils in postmortem brain tissue from PD patients as well as an α-syn transgenic mouse model for PD. The density of SIL23 binding sites correlates with the level of fibrillar α-syn in PD brain tissue, and [(125)I]SIL23 binding site densities in brain tissue are sufficiently high to enable in vivo imaging with high affinity ligands. These results identify a SIL23 binding site on α-syn fibrils that is a feasible target for development of an α-syn imaging agent. The affinity of SIL23 for α-syn and its selectivity for α-syn versus Aβ and tau fibrils is not optimal for imaging fibrillar α-syn in vivo, but we show that SIL23 competitive binding assays can be used to screen additional ligands for suitable affinity and selectivity, which will accelerate the development of an α-syn imaging agent for PD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Diagnostic Imaging / methods
  • Female
  • Humans
  • Iodine Isotopes*
  • Male
  • Mice
  • Mice, Transgenic
  • Parkinson Disease / diagnosis
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / metabolism
  • Radioligand Assay / methods
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • alpha-Synuclein / metabolism*
  • tau Proteins / metabolism


  • Iodine Isotopes
  • Radiopharmaceuticals
  • alpha-Synuclein
  • tau Proteins