Study Rationale: We developed [11C]SY08 for alpha-synuclein PET imaging. Our early findings in people showed increased brainstem binding and a trend towards increased cortical binding in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), yet limited binding in multiple systems atrophy (MSA) participants, compared to aged-matched healthy control (HC) participants. Here, we will build on our early experience to evaluate whether [11C]SY08 PET imaging will distinguish DLB, PD, and MSA from HC and will determine whether binding in DLB and PD will be higher than in MSA.
Hypothesis: We seek to determine whether [11C]SY08 PET imaging will distinguish DLB, PD, and MSA from HC and will determine whether binding in DLB and PD will be higher than in MSA.
Study Design: We will recruit PD, DLB, MSA, and HC participants to achieve sample sizes of 10 per diagnostic group. Participants will meet current clinical criteria for these diseases and will undergo skin biopsy for phosphorylated alpha-synuclein if not already acquired. Participants will undergo clinical evaluation followed by [11C]SY08 PET and simultaneous MRI. We will acquire arterial data where possible. We will pursue PET data analyses to compare uptake of [11C]SY08 across the diagnostic groups.
Impact on Diagnosis/Treatment of Parkinson’s Disease: We currently lack tools to quantitatively measure brain alpha-synuclein pathological burden in life needed for staging and for clinical trials in Parkinson’s and related synucleinopathies. We also lack tools to differentiate PD and DLB from MSA. [11C]SY08 PET has the potential to meet these needs.
Next Steps for Development: If results of this study show that [11C]SY08 PET can differentiate PD, DLB, and MSA from HC and possibly from each other, we will evaluate its binding in Alzheimer’s disease (where amyloid and 3R/4R PHF tau deposit) and PSP (where 4R tau deposits). We will also evaluate [18F]SY08 PET, as an F18 radioligand will enable multicenter studies.
Trial Phase: 0