Abstract for presentation at 38th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine 2008

Characterization of F18-BF227 Binding to α-synuclein

  • Dr Michelle Fodero-Tavoletti, Bio21 Molecular and Biotechnology Institute, University of Melbourne, Australia
  • Dr Rachel Mulligan, Department of Nuclear Medicine, Centre for P.E.T., Austin Health, Melbourne, Australia
  • Dr Nobuyuki Okamura, Department of Pharmacology, Tohoku University, Sendai, Japan
  • Dr Shozo Furumoto, Biomedical Engineering Research Organization, Tohoku University, Sendai, Japan
  • Prof Christopher Rowe, Department of Nuclear Medicine, Centre for P.E.T., Austin Health, Melbourne, Australia
  • Prof Yukitsuka Kudo, Biomedical Engineering Research Organization, Tohoku University, Sendai, Japan
  • Prof Kazuhiko Yanai, Department of Pharmacology, Tohoku University, Sendai, Japan
  • Dr Victor Villemagne, Department of Nuclear Medicine, Centre for P.E.T., Austin Health, Melbourne, Australia

    • Objectives : Aβ plaques are a pathological hallmark of Alzheimer’s disease (AD), but also occur in Dementia with Lewy Bodies (DLB). C11-PiB-PET studies have shown that the pattern of C11-PiB retention in DLB is similar to that observed for AD patients. As F18-BF227 binds with high affinity to Aβ plaques and shares some structural similarities to C11-PIB, we characterized the in vitro binding properties of F18-BF227 to Aβ42 and α-synuclein (α-syn) fibrils and AD, DLB and control brain homogenates, to investigate whether F18-BF227 binds to α-syn containing Lewy bodies, in addition to Aβ plaques.
    Methods: In vitro saturation studies comprising F18-BF227 (2-250nM) and either 200 nM α-syn or Aβ42 fibrils or 100μg of brain homogenates (AD, DLB, healthy control) were conducted. Non-specific binding was established with PiB (1μM).
    Results : In vitro binding assays indicated that F18-BF227 binds to Aβ42 and α-syn fibrils in a saturable manner. F18-BF227 exhibited affinities in the nanomolar range for Aβ42 (KD=2nM) and subnanomolar range for α-syn (KD=0.54nM). Binding of F18-BF227 to brain homogenates is currently under review.
    Conclusions : In vitro binding studies suggest that F18-BF227 may not be a very specific ligand for Aβ although the α-syn concentrations used in these studies are well above the physiological range. Further evaluation of the ligand in Parkinson’s disease brains is warranted.

    Conference Organiser - ICMS Pty Ltd