To evaluate region-specific microglial activation in Multiple System Atrophy (MSA) using [F-18]PBR06 -PET targeting 18kiloDalton-translocator protein (TSPO) and examine its association with clinical severity, regional atrophy, and survival.

MSA lacks fully validated in-vivo biomarkers for disease staging or progression monitoring. Microglial activation and neuroinflammation are consistently observed in postmortem cohorts and experimental models of MSA. Second-generation TSPO ligands such as [F-18]PBR06 enable sensitive, regional quantification of neuroinflammation in vivo.

Cross-sectional study of 18 MSA (MSA-C=12; MSA-P=6) and 9 controls. TSPO genotyping excluded low-affinity binders. [F-18]PBR06 PET images were co-registered to brain MRI and globally-normalized 60-90 minute standardized-uptake-value ratios (SUVRs) were calculated. Regional analyses used nonparametric-tests and voxel-wise statistical parametrical mapping (SPM) adjusting for age, sex, and TSPO affinity. Disease severity was assessed with the Unified MSA rating scale (UMSARS).

Compared with controls, MSA showed elevated [F-18]PBR06 uptake in the putamen (+14.1%, p=0.01), pallidum (+12.5%, p=0.006), cerebellar white matter (CWM; +9%, p=0.03), and hippocampus (+8%, p=0.04), all with large effect sizes. After covariate adjustment, differences in the putamen and pallidum remained significant. Voxel-wise SPM confirmed widespread increases across the thalamus, hippocampus, basal ganglia, and midbrain (p<0.05). Putaminal uptake correlated with both UMSARS Part II (R=0.57) and total scores (R=0.56). Regions showing elevated PET signal also exhibited marked atrophy on MRI (putamen −43%; CWM −45%), and CWM PET-uptake inversely correlated with its volume (ρ=−0.61, p=0.04). Receiver-operating-curve analyses demonstrated good discrimination between MSA and controls (AUC: pallidum 0.85; putamen 0.82). Higher putaminal SUVRs showed a trend for predicting shorter survival (HR = 1.85 per 0.1 SUVR, p=0.051)

[F-18]PBR06 TSPO-PET identifies region-specific neuroinflammation in MSA correlates with clinical severity, regional atrophy, and may have predictive value for disease course, supporting it as a promising biomarker for MSA. Larger, longitudinal studies of [F-18]PBR06-PET in MSA are warranted.