Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease
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11307_2013_Article_634.pdf
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Author(s)
Neal, Krista L.
Shakerdge, Naomi B.
Hou, Steven S.
Klunk, William E.
Mathis, Chester A.
McLean, Pamela J.
Bacskai, Brian J.
Nesterov, Evgueni
Swager, Timothy M
Date Issued
April 2013
Journal
Molecular Imaging and Biology
Publisher
Springer US
Citation
Neal, Krista L. et al. “Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease.” Molecular Imaging and Biology 15.5 (2013): 585–595.
Version
Author's final manuscript
Abstract
Purpose: 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.
Procedure: 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1007/s11307-013-0634-y
