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Title
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Validation and noninvasive kinetic modeling of UCB-J PET imaging in mice
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Author
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Abstract
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| Synaptic pathology is associated with several brain disorders, thus positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) using the radioligand [C-11]UCB-J may provide a tool to measure synaptic alterations. Given the pivotal role of mouse models in understanding neuropsychiatric and neurodegenerative disorders, this study aims to validate and characterize [C-11]UCB-J in mice. We performed a blocking study to verify the specificity of the radiotracer to SV2A, examined kinetic models using an image-derived input function (IDIF) for quantification of the radiotracer, and investigated the in vivo metabolism. Regional TACs during baseline showed rapid uptake of [C-11]UCB-J into the brain. Pretreatment with levetiracetam confirmed target engagement in a dose-dependent manner. V-T (IDIF) values estimated with one- and two-tissue compartmental models (1TCM and 2TCM) were highly comparable (r=0.999, p < 0.0001), with 1TCM performing better than 2TCM for K-1 (IDIF). A scan duration of 60 min was sufficient for reliable V-T (IDIF) and K-1 (IDIF) estimations. In vivo metabolism of [C-11]UCB-J was relatively rapid, with a parent fraction of 22.5 +/- 4.2% at 15 min p.i. In conclusion, our findings show that [C-11]UCB-J selectively binds to SV2A with optimal kinetics in the mouse representing a promising tool to noninvasively quantify synaptic density in comparative or therapeutic studies in neuropsychiatric and neurodegenerative disorder models. |
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Language
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English
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Source (journal)
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Journal of cerebral blood flow and metabolism. - New York, N.Y., 1981, currens
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Publication
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Thousand oaks
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Sage publications inc
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2019
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ISSN
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0271-678X
[print]
1559-7016
[online]
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DOI
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10.1177/0271678X19864081
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Volume/pages
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12 p.
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Article Reference
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UNSP 0271678X19864081
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ISI
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000479494700001
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Pubmed ID
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31307287
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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