Development and Screening of Contrast Agents for In Vivo Imaging of PD
Critical Challenges in PD: Alpha-synuclein Neuroimaging, 2009
The research from this grant has continued with the supplementary grant:
This project aims to develop reagents to image alpha-synuclein pathology in the brains of living patients as a PD specific biomarker.
Using a library of small molecule fluorescent compounds with properties compatible with crossing the blood-brain barrier, we will develop cell and tissue based screens to determine the suitability of using these molecules as markers of Parkinson’s pathology in the brain. Using optical approaches, we will determine which, if any, of these compounds bind to relevant alpha-synuclein aggregates in vitro, and then begin the characterization of how well the compounds enter the brain in vivo. Further characterization will include determining specificity and sensitivity, as well as toxicity. Candidate compounds would ultimately be optimized for use in clinical PET scanners.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Using clinical imaging as a biomarker of the disease will allow early detection as well as provide relevant endpoints to evaluate effectiveness of experimental drugs in clinical trials.
Our goal is to have identified several candidate compounds that bind to Parkinson’s pathology and cross blood-brain barrier. These compounds will then be developed into probes suitable for imaging with PET to allow diagnostic imaging of PD in patients.
Our goal was to screen a library of small molecule fluorescent agents as potential molecular imaging probes for PD. We employed cell culture models of alpha-synuclein aggregation and immunohistochemistry-based validation of Lewy bodies in human tissue sections. We identified several lead compounds that require further characterization. Our next steps will be to expand our screen to larger libraries of fluorescent compounds and to test the ability of our lead compounds to cross the blood-brain barrier. Once this difficult hurdle is crossed, the compounds will be evaluated in pre-clinical models of alpha-synuclein aggregation. Ultimately, the compounds will be radiolabeled and evaluated as PET agents for non-invasive imaging.
Assistant in Neurology at Massachusetts General Hospital/Harvard Medical School
Associate Professor at Mayo Clinic Jacksonville
Location: Jacksonville, Florida, United States