Project 1: Alpha Synuclein

Development of Alpha Synuclein PET Radioligands for Imaging Synucleinopathies

Project Leads: Robert H. Mach PhD, Kelvin Luk, PhD, Virginia M.-Y. Lee PhD, Paul T. Kotzbauer MD, PhD, Zhude Tu, PhD

This Project will conduct a series of in vitro binding studies, in vivo brain uptake and PET imaging studies in the process of evaluating radiotracers for imaging aggregated alpha synuclein (Asyn) in the synucleinopathies, which include Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).  The compounds evaluated in this project will be identified via in silico ultrahigh throughput screening and traditional structure-activity relationship (SAR) studies conducted in the MCRC Core. Compounds with a high affinity for Asyn and good selectivity versus other proteinopathies (Abeta, tau and TDP43) will be advanced to a series of in vitro autoradiography and in vivo studies as a means of identifying a suitable candidate(s) for translational imaging studies in humans. The ultimate goal of the research described in Project 1 is to identify radiotracers for the different synucleinopathies that will be conducted in translational imaging studies described in the Clinical Core.