$^{18}F-PBR111$ PET imaging in healthy controls and schizophrenia

Ondertitel:test retest reproducibility and quantification of neuroinflammation

Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation positron emission tomography (PET) ligand that specifically binds the TSPO, allowing in-vivo visualization and quantification of neuroinflammation. The aim of this study is to evaluate if 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 (HC) and 11 male schizophrenia patients during a psychotic episode (SP). Prior genotyping for the rs6917 polymorphism distinguished high- (HAB) and mixed-affinity binders (MAB). Total volume of distribution (VT) was determined from two-tissue compartment modeling with vascular trapping and a metabolite-corrected plasma input function. A subgroup of HCs (n = 12; 4 HAB and 8 MAB) was scanned twice to assess absolute test-retest variability and intraclass correlation coefficients (ICC) 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-60min versus VT-90min) was determined based on Pearsons r. Data was presented as 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. ICCs were consistently between 0.64 0.82 for all tested regions. TSPO binding in SP compared to 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 30 ± 8% (HC: 17 ± 5%, SP: 55 ± 13%) higher than MABs. Across all clinical groups, VT-60min and VT-90min 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.

Jaar van publicatie:2018

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:10

CSS-citation score:2

Authors from:Higher Education

Toegankelijkheid:Closed