# In Vitro and In Vivo Characterization of Alpha-Synuclein PET Radiotracers

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2020 · $1,069,406

## Abstract

PROJECT 1: Development of Alpha Synuclein PET Radioligands for Imaging Synucleinopathies
The goal of Project 1 is to 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 Medicinal
Chemistry and Radiochemistry (MCRC) Core. The in vitro binding assays described in this project will consist
of three different types: 1) screening of “in silico hits” in Asyn fibrils using radioligands for the different binding
sites with the goal of identifying “fibril confirmed hits”; 2) in vitro binding assays of the fibril confirmed hits to
identify new lead compounds having an affinity for ASyn in PD and MSA tissue of <50 nM; and, 3) indirect and
direct binding assays of compounds developed as part of the SAR studies in the MCRC Core targeting or more
of the binding sites in Asyn fibrils. Compounds having 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. Another
function of Project 1 is to cross-validate potential PET radiotracers having a high affinity for 4R tau developed by
the MCRC Core and evaluated in Project 2. The successful accomplishment of the research objectives of this
U19 Center will require the frequent communication between the members of the MCRC Core, Project 1 and
Project 2. This will be accomplished by through the series of bi-weekly teleconference calls and meetings of the
Center Steering Committee, External Liaison Committee, and NINDS program staff as outlined in the
administrative Core. 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.

## Key facts

- **NIH application ID:** 10023219
- **Project number:** 5U19NS110456-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ROBERT H MACH
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,069,406
- **Award type:** 5
- **Project period:** 2019-09-24 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023219

## Citation

> US National Institutes of Health, RePORTER application 10023219, In Vitro and In Vivo Characterization of Alpha-Synuclein PET Radiotracers (5U19NS110456-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10023219. Licensed CC0.

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