18F‐Florzolotau Positron Emission Tomography Imaging of Tau Pathology in the Living Brains of Patients with Corticobasal Syndrome

ABSTRACT Background Recent development in tau‐sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18F‐florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease‐level differences exist with other neurodegenerative tauopathies is still unanswered. Objective To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18F‐florzolotau PET imaging and to examine whether differences with other tauopathies exist. Methods 18F‐florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy–Richardson's syndrome (PSP‐RS). Cerebrospinal fluid (CSF) levels of β‐amyloid biomarkers were quantified in all patients with CBS. 18F‐florzolotau uptake was quantitatively assessed using standardized uptake value ratios. Results Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18F‐florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18F‐florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP‐RS. An asymmetric pattern of 18F‐florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. Conclusions In vivo 18F‐florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society. CBS showed increased 18F‐Florzolotau signal in both cortical and subcortical regions compared with HCs, while showed higher tracer retention in subcortical regions compared with AD, and a trend toward higher signals in cortical areas compared with PSP‐RS. 18F‐Florzolotau PET holds promise for distinguishing CBS within the spectrum of neurodegenerative tauopathies.