Preclinical PET Studies of [11C]UCB-J Binding in Minipig Brain

Purpose Loss of neuronal synapse function is associated with a number of brain disorders. The [ 11 C]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...

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Published inMolecular imaging and biology Vol. 22; no. 5; pp. 1290 - 1300
Main Authors Thomsen, Majken Borup, Schacht, Anna Christina, Alstrup, Aage Kristian Olsen, Jacobsen, Jan, Lillethorup, Thea Pinholt, Bærentzen, Simone Larsen, Noer, Ove, Orlowski, Dariusz, Elfving, Betina, Müller, Heidi Kaastrup, Brooks, David J., Landau, Anne M.
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.10.2020
Springer Nature B.V
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Summary:Purpose Loss of neuronal synapse function is associated with a number of brain disorders. The [ 11 C]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 characterise [ 11 C]UCB-J imaging in Göttingen 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 [ 11 C]UCB-J PET imaging to in vitro autoradiography, Western blotting and real-time quantitative polymerase chain reaction. Results The uptake kinetics of [ 11 C]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 [ 11 C]UCB-J binding estimates, while it was not possible to use centrum semiovale white matter as a non-specific reference region. Brain [ 11 C]UCB-J PET signals correlated well with [ 3 H]UCB-J autoradiography and SV2A protein levels. Conclusions [ 11 C]UCB-J PET is a valid in vivo marker of synaptic density 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.
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ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-020-01506-8