[18F]SynVest-1 PET imaging in people with Parkinson's disease.

The [¹⁸F]SynVest-1 radiotracer targets the synaptic vesicle glycoprotein 2A (SV2A) and is a proxy of presynaptic density. Parkinson's disease is associated with synaptic dysfunction. Here we investigated synaptic density via the [¹⁸F]SynVest-1 radiotracer in people with PD compared with healthy controls, with reference to how it compares to the previous SV2A radiotracer, [11C]UCB-J. Ten Parkinson's patients and 12 healthy subjects underwent a [¹⁸F]SynVest-1 PET scan. We compared non-displaceable binding potential via voxel-wise and volume of interest analysis to investigate group differences. Volume-of-interest-analyses reported lower non-displaceable binding potential in key a priori regions associated with Parkinson's disease, namely the substantia nigra and caudate nucleus (P < 0.05). Follow-up exploratory volume-of-interest-analyses reported widespread reduction in non-displaceable binding potential within all brain lobes, cerebellum, hippocampus, thalamus and insula; however, these findings did not survive correction for multiple comparisons (P < 0.004). In addition, voxel-wise analyses with family-wise error correction, highlighted significantly lower non-displaceable binding potential in the PD cohort within the putamen and cerebellum. We did not observe any relationships between clinical metrics and non-displaceable binding potential. The results are in line with differences observed using the [¹¹C]UCB-J radiotracer. The [¹⁸F]SynVest-1 radiotracer confirmed lower synaptic density in the Parkinson's disease cohort and adds to the growing evidence of synaptic dysfunction in Parkinson's disease pathology.