Binding of the synaptic vesicle radiotracer [¹¹C]UCB-J is unchanged during functional brain activation using a visual...

The positron emission tomography radioligand [¹¹C]UCB-J binds to synaptic vesicle glycoprotein 2 A (SV2A), a regulator of vesicle release. Increased neuronal firing could potentially affect tracer concentrations if binding site availability is altered during vesicle exocytosis. This study assessed whether physiological brain activation induces changes in [¹¹C]UCB-J tissue influx (K₁), volume of distribution (V_T), or binding potential (BP_ND). Healthy volunteers (n = 7) underwent 60-min [¹¹C]UCB-J PET scans at baseline and during intermittent presentation of 8-Hz checkerboard visual stimulation. Sensitivity to intermittent changes in kinetic parameters was assessed in simulations, and visual stimulation was repeated using functional magnetic resonance imaging to characterize neural responses. V_T  and K₁ were determined using the one-tissue compartment model and BP_ND using the simplified reference tissue model. In primary visual cortex, K₁ increased 34.3 ± 15.5% (p = 0.001) during stimulation, with no change in other regions (ps > 0.12). K₁ change was correlated with fMRI BOLD response (r = 0.77, p = 0.043). There was no change in V_T (-3.9 ± 8.8%, p = 0.33) or BP_ND (-0.2 ± 9.6%, p = 0.94) in visual cortex nor other regions (ps > 0.19). Therefore, despite robust increases in regional tracer influx due to blood flow increases, binding measures were unchanged during stimulation. [¹¹C]UCB-J V_T and BP_ND are likely to be stable in vivo measures of synaptic density.