Development and screening of contrast agents for in vivo imaging of Parkinson's disease

Krista L. Neal, Naomi B. Shakerdge, Steven S. Hou, William E. Klunk, Chester A. Mathis, Evgueni E. Nesterov, Timothy M. Swager, Pamela J. McLean, Brian J. Bacskai

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)585-595
Number of pages11
JournalMolecular Imaging and Biology
Volume15
Issue number5
DOIs
StatePublished - Oct 1 2013

Keywords

  • Alpha-Synuclein
  • Blood-brain barrier
  • Dementia with Lewy bodies
  • In vivo imaging
  • Lewy Neurites
  • Lewy bodies
  • Molecular imaging
  • PET
  • Parkinson's disease

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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  • Cite this

    Neal, K. L., Shakerdge, N. B., Hou, S. S., Klunk, W. E., Mathis, C. A., Nesterov, E. E., Swager, T. M., McLean, P. J., & Bacskai, B. J. (2013). Development and screening of contrast agents for in vivo imaging of Parkinson's disease. Molecular Imaging and Biology, 15(5), 585-595. https://doi.org/10.1007/s11307-013-0634-y