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

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 w...

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Bibliographic Details
Published in:	Journal of cerebral blood flow and metabolism 2021-05, Vol.41 (5), p.1067-1079
Main Authors:	Smart, Kelly, Liu, Heather, Matuskey, David, Chen, Ming-Kai, Torres, Kristen, Nabulsi, Nabeel, Labaree, David, Ropchan, Jim, Hillmer, Ansel T, Huang, Yiyun, Carson, Richard E
Format:	Article
Language:	eng
Subjects:	Adult Brain - diagnostic imaging Brain - metabolism Brain - physiology Brain Mapping - methods Cerebrovascular Circulation - physiology Female Humans Magnetic Resonance Imaging - methods Male Membrane Glycoproteins - metabolism Middle Aged Nerve Tissue Proteins - metabolism Original Photic Stimulation - adverse effects Photic Stimulation - methods Positron-Emission Tomography - methods Protein Binding - radiation effects Radiopharmaceuticals - metabolism Synaptic Vesicles - metabolism
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Summary:	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.
ISSN:	0271-678X 1559-7016