Imaging Agents

The ability to monitor alpha-synuclein fibril levels in living individuals with PD will be essential to guide the development of therapeutics that target the abnormal alpha-synuclein accumulation. We hypothesize that ligands that bind alpha-synuclein fibrils could be utilized as imaging agents to improve both the diagnosis of PD, as well as to monitor disease progression. To promote the development of these high affinity alpha-synuclein ligands, we have developed methods to characterize the binding of several classes of small molecule compounds to alpha-synculein fibrils in postmortem PD brain tissue. We are currently screening additional ligands as part of the Michael J. Fox Foundation Alpha-Synuclein Imaging Consortium, and have identified several promising compounds for potential use as PD imaging agents. 

Additionally, we are also in the process of identifying imaging agents for amyloid beta (Abeta) fibrils, which will be valuable not only for PD, but also for Alzheimer's disease. Utilizing the methods we developed for screening alpha-synuclein ligands in PD, we are collaborating with Dr. Vijay Sharma at Washington University to identify sensitive novel Abeta imaging agents in order to detect early accumulation of Abeta.

 

SELECT Publications

  1. Sundaram GS, Dhavale DD, Prior JL, Yan P, Cirrito J, Rath NP, Laforest R, Cairns NJ, Lee JM, Kotzbauer PT, Sharma V. (2016). Fluselenamyl: A Novel Benzoselenazole Derivative for PET Detection of Amyloid Plaques (Aβ) in Alzheimer's Disease. Sci Rep. 6:35636. PubMed PMID: 27805057.
     
  2. Sundaram GS, Dhavale D, Prior JL, Sivapackiam J, Laforest R, Kotzbauer P, Sharma V. (2015). Synthesis, characterization, and preclinical validation of a PET radiopharmaceutical for interrogating Aβ (β-amyloid) plaques in Alzheimer's disease. EJNMMI Res. 5(1):112. PubMed PMID: 26061601.
     
  3. Chu W, Zhou D, Gaba V, Liu J, Li S, Peng X, Xu J, Dhavale D, Bagchi DP, d'Avignon A, Shakerdge NB, Bacskai BJ, Tu Z, Kotzbauer PT, Mach RH. (2015). Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for α-Synuclein Fibrils. J Med Chem. 58(15):6002-3017. PubMed PMID: 26177091.
     
  4. Bagchi DP, Yu L, Perlmutter JS, Xu J, Mach RH, Tu Z, Kotzbauer PT. (2013). Binding of the radioligand SIL23 to α-synuclein fibrils in Parkinson disease brain tissue establishes feasibility and screening approaches for developing a Parkinson disease imaging agent. PLoS One. 8(2):e55031. PubMed PMID: 23405108.