title: Development and screening of contrast agents for in vivo imaging of Parkinson's disease.
abstract: OBJECTIVE
  The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson's disease (PD) pathology, and be detectable with one or more imaging modalities.
  
  
  METHODS
  A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson's and Alzheimer's disease tissue, alpha-synuclein oligomers and inclusions in two cell culture models, and alpha-synuclein aggregates in cortical neurons of a transgenic mouse model. Finally, compounds were tested for blood-brain barrier permeability using intravital microscopy.
  
  
  RESULTS
  Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer's pathology. The cell culture models and transgenic mouse models that exhibit alpha-synuclein aggregation did not prove predictive for ligand binding. The compounds had favorable physicochemical properties, and several were brain permeable.
  
  
  CONCLUSIONS
  Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology.
authors.affiliation: MassGeneral Institute of Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street, Charlestown, MA, 02129, USA.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Neal
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Shakerdge
authors.forename: Steven S
authors.initials: SS
authors.lastname: Hou
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: Evgueni E
authors.initials: EE
authors.lastname: Nesterov
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Swager
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: McLean
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000473:pathology; D002478:Cells, Cultured; D003199:Computer Systems; D003287:Contrast Media / Q000032:analysis* / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D010300:Parkinson Disease / Q000175:diagnosis* / Q000473:pathology; D010539:Permeability; D013194:Staining and Labeling; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003287:Contrast Media; D008164:Luminescent Proteins; D051844:alpha-Synuclein; C054562:yellow fluorescent protein, Bacteria