Study of Biodistribution, Metabolism, Excretion and Brain Uptake11C-M503

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 11C-M503. The goal of this radiotracer is to quantify alpha-synuclein that is abnormally deposited in the brain of people with Parkinson's disease (PD). Investigators will compare uptake in participants with PD versus participants with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as well as non-Parkinsonism volunteers. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt) (non-clinical site) Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites. Participating clinical sites will recruit up to 20 people with PD, 20 with MSA, 10 with PSP and 20 healthy controls across sites with all participants ranging from 40-85 years old. Investigators will encourage equal participation of males and females. This protocol will include up to 70 participants across all clinical sites (note that some of these participant scans performed at Penn may be used to calculate whole body biodistribution (BioD) and dosimetry. Investigators anticipate enrollment of up to 15-20 participants at each clinical site, who will undergo up to 120 minutes of dynamic brain PET scanning (with or without torso imaging, depending on the clinical site). A second IV or an arterial line may be placed, preferably in the arm contralateral to the side of injection, for blood metabolite analysis and/or radioactive counts at various times during the scanning session. These blood draw collections can be omitted at the discretion of the investigator. For participants at Penn that may be part of BioD analysis, urine may be collected at the end of the scan session. Participants will also undergo a research brain MRI that may be on a separate day from the PET. PET imaging sessions will include an injection of ≤ 15 mCi (approximate range for most studies is anticipated to be 8 - 15 mCi at sites with a standard PET scanner or 3 - 15 at sites with a high sensitivity scanner) of 11C-M503. Biodistribution, metabolism, excretion and pilot brain uptake data will be collected and human dosimetry will be calculated from participants scanned at Penn who have whole body scans. PET scans will be collected to evaluate image quality and collect preliminary information on brain uptake of 11C-M503 in the disease cohorts and healthy controls. The safety of 11C-M503 will also be evaluated in all participants. Some participants (usually those with positive 11C-M503 PET scan) may also be asked to have an amyloid-beta (Aβ) PET scan to investigate specificity of 11C-M503.