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Lookup NU author(s): Professor David BrooksORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Springer, 2020.
For re-use rights please refer to the publisher's terms and conditions.
Purpose: Loss of neuronal synapse function is associated with a number of brain disorders. The [11C]UCB-J positron emission tomography (PET) tracer allows for in vivo examination of synaptic density, as it binds to synaptic vesicle glycoprotein 2A (SV2A) expressed in presynaptic terminals. Here we characterize [11C]UCB-J imaging in G.ttingen minipigs. Procedures: Using PET imaging, we examined tracer specificity and compared kinetic models. We explored the use of a standard blood curve and centrum semiovale white matter as a reference region. We compared in vivo [11C]UCBJ PET imaging to in vitro autoradiography, Western blotting and real-time quantitative polymerase chain reaction. Results: The uptake kinetics of [11C]UCB-J could be described using a 1-tissue compartment model and blocking of SV2A availability with levetiracetam showed dose-dependent specific binding. Population-based blood curves resulted in reliable [11C]UCB-J binding estimates, while it was not possible to use centrum semiovale white matter as a non-specific reference region. Brain [11C]UCB-J PET signals correlated well with [3H]UCB-J autoradiography and SV2A protein levels. Conclusions: [11C]UCB-J PET is a valid in vivo marker of synaptic integrity in the minipig brain, with binding values close to those reported for humans Minipig models of disease could be valuable for investigating the efficacy of putative neuroprotective agents for preserving synaptic function in future non-invasive, longitudinal studies. .
Author(s): Thomsen MB, Schacht MC, Alstrup AKO, Lillethorup TP, Baerentzen SL, Noer O, Brooks DJ, Landau AM
Publication type: Article
Publication status: Published
Journal: Molecular Imaging and Biology
Year: 2020
Volume: 22
Pages: 1290-1300
Print publication date: 01/10/2020
Online publication date: 08/06/2020
Acceptance date: 06/05/2020
Date deposited: 06/05/2020
ISSN (print): 1536-1632
ISSN (electronic): 1860-2002
Publisher: Springer
URL: https://doi.org/10.1007/s11307-020-01506-8
DOI: 10.1007/s11307-020-01506-8
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