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IMAGING OF TAU PATHOLOGY IN PATIENTS WITH NON-ALZHEIMER'S DISEASE TAUOPATHIES BY [11C]PBB3-PET

      Background: [11 C]PBB3 has been recently developed as a tau imaging PET ligand.The preclinical studies showed high affinity and selectivity of this ligand for tau deposits. Our initial PET study with [11 C]PBB3 demonstrated high [11 C]PBB3 binding in the cerebral cortex including medial temporal lobes in patients with Alzheimer's disease (AD) compared with age-matched controls. The aim of this study is to test the hypothesis that [11 C]PBB3 PET is a sensitive in vivo imaging method for detecting tau lesions in non-AD tauopathies such as progressive supranuclar palsy (PSP) and corticobasal degeneration (CBD).
      Methods: Ten patients with PSP, five patients with corticobasal syndrome (CBS), and 18 age-matched healthy controls (HCs) participated in this study. Sequential PET scans were performed for 70 min following intravenous injection of [11 C]PBB3. PET images were anatomically normalized to the Montreal Neurological Institute space using T1 weighted MRI, and standardized uptake value ratio (SUVR) was calculated using the cerebellar cortex as reference region. One-way ANOVA test was performed among PSP, CBS patients, and HCs using statistical parametric mapping software (SPM 8). Statistical threshold was set to 0.01 with extent threshold of 50 voxels without correction for multiple comparisons. Cerebral beta-amyloid depositions were also estimated using SUVR images at 50-70 min after [11 C]Pittsburgh compound B injection in all patients and HCs.
      Results: All patients and HCs were PIB-negative except one PIB-positive patient with CBS and one HC. SPM analysis showed high [11 C]PBB3 binding in globus pallidus, putamen, thalamus, subthalamus, midbrain, pons, and peri-rolandic areas in PSP patients compared with HCs. PIB-negative CBS patients (n=4) showed high [11 C]PBB3 binding in peri-rolandic areas, supplementary motor area, subthalamus, and midbrain compared with HCs. SUVR images of one PIB-positive patient with CBS showed high [11 C]PBB3 binding in the whole cerebral cortex including limbic cortex like advanced AD patients.
      Conclusions: The distribution of [11 C]PBB3 binding in the patients was in accord with the known distribution of tau pathology in PSP and CBD. The present study supports the utility of [11 C]PBB3-PET for detecting tau deposition in non-AD tauopathies including PSP and CBD.