Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 38, Issue 11, Pages 2041-2052Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X17724947
Keywords
Brain imaging; kinetic modeling; neurodegeneration; positron emission tomography; synapses/dendrites
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Funding
- UCB Pharma
- Swedish Research Council
- CTSA from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH) [UL1 TR000142]
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Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [C-11]UCB-J in humans. Five volunteers were examined twice on the HRRT after bolus injection of [C-11]UCB-J. Arterial blood samples were collected for measurements of radiometabolites and free fraction. Regional time-activity curves were analyzed with 1-tissue (1T) and 2-tissue (2T) compartment models to estimate volumes of distribution (V-T). Parametric maps were generated using the 1T model. [C-11]UCB-J metabolized fairly quickly, with parent fraction of 36 +/- 13% at 15 min after injection. Plasma free fraction was 32 +/- 1%. Regional time-activity curves displayed rapid kinetics and were well described by the 1T model, except for the cerebellum and hippocampus. V-T values estimated with the 2T model were similar to 1T values. Parametric maps were of high quality and V-T values correlated well with time activity curve (TAC)-based estimates. Shortening of acquisition time from 120 min to 60 min had a negligible effect on V-T values. The mean absolute test-retest reproducibility for V-T was 3-9% across regions. In conclusion, [C-11]UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative disorders.
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