18 F-PBR111 PET Imaging in Healthy Controls and Schizophrenia: Test-Retest Reproducibility and Quantification of Neuroinflammation.

Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. ¹⁸ F-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 ¹⁸ F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min ¹⁸ F-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 (V _T ) 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 V _T 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 (V _{T-60 min} versus V _{T-90 min} ) was determined based on Pearson r. Data were mean ± SD. Results: Mean absolute variability in V _T 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 V _T of HABs was 31% ± 8% (HC: 17% ± 5%, SP: 61% ± 14%) higher than MABs. Across all clinical groups, V _{T-60 min} and V _{T-90 min} were strongly correlated ( r > 0.7, P < 0.0001). Conclusion: ¹⁸ F-PBR111 can be used for monitoring of TSPO binding, as shown by medium test-retest variability and reliability of V _T in HCs. Microglial activation is present in SPs depending on age and needs to be adjusted for genotype.
(© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)