Julie Ottoy1, Livia De Picker2,3, Jeroen Verhaeghe1, Steven Deleye1, Leonie Wyffels4, Lauren Kosten1, Bernard Sabbe2,3, Violette Coppens2,3, Maarten Timmers5,6, Luc van Nueten5, Sarah Ceyssens4, Sigrid Stroobants4, Manuel Morrens2,3, Steven Staelens7. 1. Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium. 2. Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium. 3. University Department of Psychiatry, Campus Duffel, Duffel, Belgium. 4. Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium. 5. Janssen Research and Development, Janssen Pharmaceutica N.V., Beerse, Belgium; and. 6. Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. 7. Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium steven.staelens@uantwerpen.be.
Abstract
Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation PET ligand that specifically binds the TSPO, allowing in vivo visualization and quantification of neuroinflammation. The aim of this study was to evaluate whether the test-retest variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F-PBR111 scans were obtained in 17 healthy male controls (HCs) and 11 male schizophrenia patients (SPs) during a psychotic episode. Prior genotyping for the rs6917 polymorphism distinguished high-affinity binders (HABs) and mixed-affinity binders (MABs). Total volume of distribution (VT) was determined from 2-tissue-compartment modeling with vascular trapping and a metabolite-corrected plasma input function. A subgroup of HCs (n = 12; 4 HABs and 8 MABs) was scanned twice to assess absolute test-retest variability and intraclass correlation coefficients of the regional VT values. Differences in TSPO binding between HC and SP were assessed using mixed model analysis adjusting for age, genotype, and age*cohort. The effect of using different scan durations (VT-60 min versus VT-90 min) was determined based on Pearson r. Data were mean ± SD. Results: Mean absolute variability in VT ranged from 16% ± 14% (19% ± 20% HAB; 15% ± 11% MAB) in the cortical gray matter to 22% ± 15% (23% ± 15% HAB; 22% ± 16% MAB) in the hippocampus. Intraclass correlation coefficients were consistently between 0.64 and 0.82 for all tested regions. TSPO binding in SP compared with HC depended on age (cohort*age: P < 0.05) and was increased by +14% ± 4% over the regions. There was a significant effect of genotype on TSPO binding, and VT of HABs was 31% ± 8% (HC: 17% ± 5%, SP: 61% ± 14%) higher than MABs. Across all clinical groups, VT-60 min and VT-90 min were strongly correlated (r > 0.7, P < 0.0001). Conclusion: 18F-PBR111 can be used for monitoring of TSPO binding, as shown by medium test-retest variability and reliability of VT in HCs. Microglial activation is present in SPs depending on age and needs to be adjusted for genotype.
Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation PET ligand that specifically binds the TSPO, allowing in vivo visualization and quantification of neuroinflammation. The aim of this study was to evaluate whether the test-retest variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F-PBR111 scans were obtained in 17 healthy male controls (HCs) and 11 male schizophreniapatients (SPs) during a psychotic episode. Prior genotyping for the rs6917 polymorphism distinguished high-affinity binders (HABs) and mixed-affinity binders (MABs). Total volume of distribution (VT) was determined from 2-tissue-compartment modeling with vascular trapping and a metabolite-corrected plasma input function. A subgroup of HCs (n = 12; 4 HABs and 8 MABs) was scanned twice to assess absolute test-retest variability and intraclass correlation coefficients of the regional VT values. Differences in TSPO binding between HC and SP were assessed using mixed model analysis adjusting for age, genotype, and age*cohort. The effect of using different scan durations (VT-60 min versus VT-90 min) was determined based on Pearson r. Data were mean ± SD. Results: Mean absolute variability in VT ranged from 16% ± 14% (19% ± 20% HAB; 15% ± 11% MAB) in the cortical gray matter to 22% ± 15% (23% ± 15% HAB; 22% ± 16% MAB) in the hippocampus. Intraclass correlation coefficients were consistently between 0.64 and 0.82 for all tested regions. TSPO binding in SP compared with HC depended on age (cohort*age: P < 0.05) and was increased by +14% ± 4% over the regions. There was a significant effect of genotype on TSPO binding, and VT of HABs was 31% ± 8% (HC: 17% ± 5%, SP: 61% ± 14%) higher than MABs. Across all clinical groups, VT-60 min and VT-90 min were strongly correlated (r > 0.7, P < 0.0001). Conclusion: 18F-PBR111 can be used for monitoring of TSPO binding, as shown by medium test-retest variability and reliability of VT in HCs. Microglial activation is present in SPs depending on age and needs to be adjusted for genotype.
Authors: Jeffrey H Meyer; Simon Cervenka; Min-Jeong Kim; William C Kreisl; Ioline D Henter; Robert B Innis Journal: Lancet Psychiatry Date: 2020-10-21 Impact factor: 27.083
Authors: Kornelis S M van der Geest; Maria Sandovici; Pieter H Nienhuis; Riemer H J A Slart; Peter Heeringa; Elisabeth Brouwer; William F Jiemy Journal: Front Med (Lausanne) Date: 2022-06-06
Authors: Pontus Plavén-Sigray; Granville J Matheson; Jennifer M Coughlin; Sina Hafizi; Heikki Laurikainen; Julie Ottoy; Livia De Picker; Pablo Rusjan; Jarmo Hietala; Oliver D Howes; Romina Mizrahi; Manuel Morrens; Martin G Pomper; Simon Cervenka Journal: Biol Psychiatry Date: 2020-07-15 Impact factor: 13.382