Development and Screening of Contrast Agents for In Vivo Imaging of Parkinson%26apos;s Disease

作者：Neal Krista L; Shakerdge Naomi B; Hou Steven S; Klunk William E; Mathis Chester A; Nesterov Evgueni E; Swager Timothy M; McLean Pamela J; Bacskai Brian J^*

来源：Molecular Imaging and Biology, 2013, 15(5): 585-595.

DOI：10.1007/s11307-013-0634-y

• Parkinson%26apos
• s disease
• Dementia with Lewy bodies
• Lewy bodies
• Lewy Neurites
• Alpha-Synuclein
• Blood-brain barrier
• In vivo imaging
• Molecular imaging
• PET

The goal was to identify molecular imaging probes that would enter the brain, selectively bind to Parkinson%26apos;s disease (PD) pathology, and be detectable with one or more imaging modalities. %26lt;br%26gt;A library of organic compounds was screened for the ability to bind hallmark pathology in human Parkinson%26apos;s and Alzheimer%26apos;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. %26lt;br%26gt;Several lead compounds were identified that bound the human PD pathology, and some showed selectivity over Alzheimer%26apos;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. %26lt;br%26gt;Future experiments will focus on more extensive evaluation of the lead compounds as PET ligands for clinical imaging of PD pathology.

• 出版日期2013-10