DAT SPECT is a known diagnostic tool for Parkinsonian syndromes, showing strong effects in the striatum over the natural course of the disease, corresponding to a reduction in dopamine transporter density and therefore correlated with dopaminergic neuronal loss. A relatively recent alternative using PET utilizes a different radiotracer that targets VMAT2, which is responsible for packaging neurotransmitters (e.g. dopamine) into presynaptic vesicles. An aim of this work has been to compare DAT SPECT with VMAT2 PET using data from the Parkinson's Progression Markers Initiative (PPMI) study. Another aim has been to look at the natural history of the disease using those imaging methods in known affected striatum regions to determine the sample sizes needed to run a therapeutic clinical using those biomarkers.

By using both the exploratory voxel-wise and regional SBR analyses, we have shown:

• The effects observed with DAT SPECT, while strong, have much lower spatial resolution than VMAT2 PET and have greater variability.
• Despite not showing significant voxelwise effects after 12 months, VMAT2 PET regional SBR analysis detected significant effects after 12 months, as early as DAT SPECT, and in both cases effects were strongest in the putamen.
• With 12 to 24 months of follow-up, sample sizes estimated to be needed in a clinical trial are less than 50 participants per arm for DAT SPECT, and as little as 10 subjects per arm with VMAT2 PET.