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Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study
OBJECTIVE: The mitochondrial 18-kDa translocator protein (TSPO) is expressed by activated microglia and positron emission tomography enables the measurement of TSPO levels in the brain. Findings in schizophrenia have shown to vary depending on the outcome measure used and this discrepancy in TSPO re...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440284/ https://www.ncbi.nlm.nih.gov/pubmed/33825022 http://dx.doi.org/10.1007/s00259-021-05327-x |
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author | Marques, Tiago Reis Veronese, Mattia Owen, David R. Rabiner, Eugenii A. Searle, Graham E. Howes, Oliver D. |
author_facet | Marques, Tiago Reis Veronese, Mattia Owen, David R. Rabiner, Eugenii A. Searle, Graham E. Howes, Oliver D. |
author_sort | Marques, Tiago Reis |
collection | PubMed |
description | OBJECTIVE: The mitochondrial 18-kDa translocator protein (TSPO) is expressed by activated microglia and positron emission tomography enables the measurement of TSPO levels in the brain. Findings in schizophrenia have shown to vary depending on the outcome measure used and this discrepancy in TSPO results could be explained by lower non-displaceable binding (V(ND)) in schizophrenia, which could obscure increases in specific binding. In this study, we have used the TSPO ligand XBD173 to block the TSPO radioligand [(11)C]-PBR28 and used an occupancy plot to quantify V(ND) in patients with schizophrenia. METHODS: A total of 7 patients with a diagnosis of schizophrenia were recruited for this study. Each patient received two separate PET scans with [(11)C]PBR28, one at baseline and one after the administration of the TSPO ligand XBD173. All patients were high-affinity binders (HABs) for the TSPO gene. We used an occupancy plot to quantify the non-displaceable component (V(ND)) using 2TCM kinetic estimates with and without vascular correction. Finally we computed the V(ND) at a single subject level using the SIME method. RESULTS: All patients showed a global and generalized reduction in [(11)C]PBR28 uptake after the administration of XBD173. Constraining the V(ND) to be equal for all patients, the population V(ND) was estimated to be 1.99 mL/cm(3) (95% CI 1.90 to 2.08). When we used vascular correction, the fractional TSPO occupancy remained similar. CONCLUSIONS: In schizophrenia patients, a substantial component of the [(11)C]PBR28 signal represents specific binding to TSPO. Furthermore, the V(ND) in patients with schizophrenia is similar to that previously reported in healthy controls. These results suggest that changes in non-specific binding between schizophrenia patients and healthy controls do not account for discrepant PET findings in this disorder. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05327-x. |
format | Online Article Text |
id | pubmed-8440284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-84402842021-10-01 Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study Marques, Tiago Reis Veronese, Mattia Owen, David R. Rabiner, Eugenii A. Searle, Graham E. Howes, Oliver D. Eur J Nucl Med Mol Imaging Original Article OBJECTIVE: The mitochondrial 18-kDa translocator protein (TSPO) is expressed by activated microglia and positron emission tomography enables the measurement of TSPO levels in the brain. Findings in schizophrenia have shown to vary depending on the outcome measure used and this discrepancy in TSPO results could be explained by lower non-displaceable binding (V(ND)) in schizophrenia, which could obscure increases in specific binding. In this study, we have used the TSPO ligand XBD173 to block the TSPO radioligand [(11)C]-PBR28 and used an occupancy plot to quantify V(ND) in patients with schizophrenia. METHODS: A total of 7 patients with a diagnosis of schizophrenia were recruited for this study. Each patient received two separate PET scans with [(11)C]PBR28, one at baseline and one after the administration of the TSPO ligand XBD173. All patients were high-affinity binders (HABs) for the TSPO gene. We used an occupancy plot to quantify the non-displaceable component (V(ND)) using 2TCM kinetic estimates with and without vascular correction. Finally we computed the V(ND) at a single subject level using the SIME method. RESULTS: All patients showed a global and generalized reduction in [(11)C]PBR28 uptake after the administration of XBD173. Constraining the V(ND) to be equal for all patients, the population V(ND) was estimated to be 1.99 mL/cm(3) (95% CI 1.90 to 2.08). When we used vascular correction, the fractional TSPO occupancy remained similar. CONCLUSIONS: In schizophrenia patients, a substantial component of the [(11)C]PBR28 signal represents specific binding to TSPO. Furthermore, the V(ND) in patients with schizophrenia is similar to that previously reported in healthy controls. These results suggest that changes in non-specific binding between schizophrenia patients and healthy controls do not account for discrepant PET findings in this disorder. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05327-x. Springer Berlin Heidelberg 2021-04-06 2021 /pmc/articles/PMC8440284/ /pubmed/33825022 http://dx.doi.org/10.1007/s00259-021-05327-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Marques, Tiago Reis Veronese, Mattia Owen, David R. Rabiner, Eugenii A. Searle, Graham E. Howes, Oliver D. Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study |
title | Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study |
title_full | Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study |
title_fullStr | Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study |
title_full_unstemmed | Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study |
title_short | Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study |
title_sort | specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11c]-pbr28 blocking study |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440284/ https://www.ncbi.nlm.nih.gov/pubmed/33825022 http://dx.doi.org/10.1007/s00259-021-05327-x |
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