Veronese, Mattia
Reis Marques, Tiago
Bloomfeld, Peter S
Rizzo, Gaia
Singh, Nisha
Jones, Deborah
Agushi, Erjon
Mosses, Dominic
Bertoldo, Allessandra
Howes, Oliver
Roncaroli, Federico
Turkheimer, Frederico F
2017-06-05
<p>The 18 kDa translocator protein (TSPO) is a marker of microglia activation in the central nervous system and represents the main target of radiotracers for the in vivo quantification of neuroinflammation with positron emission tomography (PET). TSPO PET is methodologically challenging given the heterogeneous distribution of TSPO in blood and brain. Our previous studies with the TSPO tracers [<sup>11</sup>C]PBR28 and [<sup>11</sup>C]PK11195 demonstrated that a model accounting for TSPO binding to the endothelium improves the quantification of PET data. Here, we performed a validation of the kinetic model with the additional endothelial compartment through a displacement study. Seven subjects with schizophrenia, all high-affinity binders, underwent two [<sup>11</sup>C]PBR28 PET scans before and after oral administration of 90 mg of the TSPO ligand XBD173. The addition of the endothelial component provided a signal compartmentalization much more consistent with the underlying biology, as only in this model, the blocking study produced the expected reduction in the tracer concentration of the specific tissue compartment, whereas the non-displaceable compartment remained unchanged. In addition, we also studied TSPO expression in vessels using 3D reconstructions of histological data of frontal lobe and cerebellum, demonstrating that TSPO positive vessels account for 30% of the vascular volume in cortical and white matter.</p>
https://doi.org/10.1177/0271678X17712388
oai:zenodo.org:906142
Zenodo
https://zenodo.org/communities/inmind
https://zenodo.org/communities/eu
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
Journal of Cerebral Blood Flow and Metabolism, (2017-06-05)
3D modelling
TSPO
XBD173
[11C]PBR28
endothelium
immunohistochemistry
kinetic modelling
Kinetic modelling of [11C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis
info:eu-repo/semantics/article