Kinetic modelling of [(11)C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis
| Autor: | Federico Roncaroli, Dominic Mosses, Deborah Jones, Alessandra Bertoldo, Nisha Singh, Federico Turkheimer, Gaia Rizzo, Erjon Agushi, Tiago Reis Marques, Mattia Veronese, Peter S. Bloomfield, Oliver D. Howes |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty endothelium Endothelium Pyridines Central nervous system Models Neurological Administration Oral 03 medical and health sciences 0302 clinical medicine Receptors GABA Cerebellum Acetamides Journal Article medicine Translocator protein Humans Radioactive Tracers [11C]PBR28 Neuroinflammation Microglia biology medicine.diagnostic_test Original Articles Compartmentalization (psychology) Middle Aged Ligand (biochemistry) 3D modelling Frontal Lobe Kinetics 030104 developmental biology medicine.anatomical_structure Neurology Positron emission tomography Purines immunohistochemistry kinetic modelling TSPO XBD173 Neurology (clinical) Cardiology and Cardiovascular Medicine Positron-Emission Tomography biology.protein Biophysics 030217 neurology & neurosurgery |
| Zdroj: | Veronese, M, Reis Marques, T, Bloomfield, P S, Rizzo, G, Singh, N, Jones, D, Agushi, E, Mosses, D, Bertoldo, A, Howes, O, Roncaroli, F & Turkheimer, F E 2017, ' Kinetic modelling of [(11)C]PBR28 for 18 kDa translocator protein PET data : A validation study of vascular modelling in the brain using XBD173 and tissue analysis ', Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism . https://doi.org/10.1177/0271678X17712388 |
| DOI: | 10.1177/0271678X17712388 |
| Popis: | 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 [11C]PBR28 and [11C]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 [11C]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. |
| Databáze: | OpenAIRE |
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