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Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task
- Source :
- J Cereb Blood Flow Metab
- Publication Year :
- 2020
- Publisher :
- SAGE Publications, 2020.
-
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.
- 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
Subjects
Details
- ISSN :
- 15597016 and 0271678X
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Accession number :
- edsair.doi.dedup.....575cd00928aa02292925e3fb7b6ded87