1. Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task
- Author
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Kristen Torres, Ansel T. Hillmer, Nabeel Nabulsi, Ming-Kai Chen, David Matuskey, Heather Liu, Jim Ropchan, Yiyun Huang, David Labaree, Kelly Smart, and Richard E. Carson
- Subjects
Adult ,Male ,Regulator ,Nerve Tissue Proteins ,Stimulation ,Synaptic vesicle ,03 medical and health sciences ,0302 clinical medicine ,Radioligand ,medicine ,Humans ,030304 developmental biology ,SV2A ,chemistry.chemical_classification ,Brain Mapping ,0303 health sciences ,Membrane Glycoproteins ,medicine.diagnostic_test ,Chemistry ,Vesicle ,Brain ,Original Articles ,Middle Aged ,Magnetic Resonance Imaging ,Neurology ,Positron emission tomography ,Cerebrovascular Circulation ,Positron-Emission Tomography ,Biophysics ,Female ,Synaptic Vesicles ,Neurology (clinical) ,Radiopharmaceuticals ,Cardiology and Cardiovascular Medicine ,Glycoprotein ,Photic Stimulation ,030217 neurology & neurosurgery ,Protein Binding - Abstract
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 ( VT), or binding potential ( BPND). 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. VT and K1 were determined using the one-tissue compartment model and BPND 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 VT (−3.9 ± 8.8%, p = 0.33) or BPND (−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 VT and BPND are likely to be stable in vivo measures of synaptic density.
- Published
- 2020