Translocator Protein 18kDa (TSPO) Expression in Patients with Clinically Diagnosed Progressive Supranuclear Palsy

Objectives: Progressive supranuclear palsy (PSP) is a 4R tauopathy with a severe clinical course, lacking sufficient treatment options. Microglial activation occurs in PSP as one pathophysiological hallmark of the disease and may serve as a therapeutic target. Therefore, we aimed to study microglial activation by the third generation 18kD translocator protein (TSPO) PET ligand [18F]GE180.

Methods: Five patients (age 68±8y, 3F) with probable PSP according to current diagnostic criteria underwent TSPO PET scanning. PET scans were acquired 60-80 min p. i. and were coregistered to the individual MRI. Seven healthy age-matched individuals (HC) served as controls. Standardized uptake value ratios (SUVR) in predefined brain regions were generated using the cerebellar cortex as reference region. The coefficient of variance (CoV) was calculated to investigate homogeneity of PET findings. Additionally, disease severity measured by the PSP Rating Scale (PSPRS) and disease duration were obtained and correlated with PET findings. Results: Significantly increased [18F]GE180 binding in PSP versus HC was found in the frontal lobe (+29%, p < 0.005), globus pallidus (+20%, p < 0.01), and the midbrain (+17%, p < 0.05). The signal increase was very homogeneous in the frontal lobe (CoV: 5%), whereas globus pallidus and the midbrain indicated a larger heterogeneity (CoV: 11-12%). Visual analysis mirrored this finding as only two subjects presented with a clear delineation of microglial activity in the midbrain. The observed heterogeneity was not associated with PSPRS or disease duration in this limited dataset. Conclusions: In this ongoing study TSPO PET binding patterns correlated well with brain regions known to be affected by PSP at autopsy. Midbrain and globus pallidus indicated a large heterogeneity of microglial activity in individual patients. [18F]GE180 seems to be a useful biomarker of microglial activity in PSP and may help to stratify patients for immunomodulatory Treatments.

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