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Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease

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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.

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Acknowledgments

Many thanks to Julia George, University of Illinois, for the H3C Antibody and to Eliezer Masliah, UCSD, for the Syn-GFP mouse model.

Funding

Michael J. Fox Foundation and NIH AG026240.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. MassGeneral Institute of Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street, Charlestown, MA, 02129, USA

    Krista L. Neal, Naomi B. Shakerdge, Steven S. Hou & Brian J. Bacskai

  2. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15260, USA

    William E. Klunk & Chester A. Mathis

  3. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Evgueni E. Nesterov & Timothy M. Swager

  4. Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA

    Pamela J. McLean

  5. Department of Chemistry, Louisiana State University, Baton Rouge, LA, 70803, USA

    Evgueni E. Nesterov

Authors
  1. Krista L. Neal
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  2. Naomi B. Shakerdge
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  3. Steven S. Hou
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  4. William E. Klunk
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  5. Chester A. Mathis
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  6. Evgueni E. Nesterov
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  7. Timothy M. Swager
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  8. Pamela J. McLean
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  9. Brian J. Bacskai
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Corresponding author

Correspondence to Brian J. Bacskai.

Additional information

Krista L. Neal and Naomi B. Shakerdge contributed equally to this work.

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Neal, K.L., Shakerdge, N.B., Hou, S.S. et al. Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson’s Disease. Mol Imaging Biol 15, 585–595 (2013). https://doi.org/10.1007/s11307-013-0634-y

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  • DOI: https://doi.org/10.1007/s11307-013-0634-y

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