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
Creators
- 1. Department of Neuroimaging, IoPPN, King's College London, London, UK
- 2. Department of Psychosis Studies, IoPPN, King's College London, London, UK and Institute of Clinical Sciences, Imperial College London, London, UK
- 3. Institute of Clinical Sciences, Imperial College London, London, UK
- 4. Department of Information Engineering, Padova University, Padova, Italy
- 5. Department of Cellular Pathology, Salford Royal Foundation Trust, Salford, UK
- 6. Division of Neuroscience and Experimental Psychology, University of Manchester, UK
- 7. Department of Information Engineering, Padova University, Padova, Italy and Padua Neuroscience Center, University of Padova, Padova, Italy
Description
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.
Files
Veronese_JCBFM_2017-P18a-AAM-v1.pdf
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(3.0 MB)
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