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

Abstract

A BS TRACT: Background: Recent development in tau-sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18 Fflorzolotau 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 18 F-florzolotau PET imaging and to examine whether differences with other tauopathies exist. Methods: 18 F-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. 18 Fflorzolotau 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 18 F-florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18 F-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 18 F-florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. Conclusions: In vivo 18 F-florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of

In vivo PET classification of tau pathologies in patients with frontotemporal dementia

“… 4 Moreover, 4RT deposits were indicated in two of three subjects with CBS and in one subject with FTD-PSP clinical phenotype. The radio signal distribution in these subjects was similar to the previous tau PET findings in patients with PSP and putative CBD, 20 , 37 , 38 , 47 whereas the distinction between PSP and CBD tau topologies was not so distinct. Besides primary tauopathies and non-tau proteinopathies, enhanced tau PET radio signals were acquired in all patients with Aβ-positive —in four subjects with bvFTD and one subject with CBS.…”

Tau in Atypical Parkinsonisms: A Meta‐Analysis of in Vivo PET Imaging Findings

“…44,45 Data for [ 18 F]PM-PBB3 tracer binding to the SN was insufficient for the present model, but recent literature states that this tracer has mediated many of the off-target binding issues observed with first-generation tracers, including off-target binding to the SN. 46,47 Our second finding was that when comparing parkinsonisms head-to-head, there was significantly higher binding to PSP patients over PD when using the first-generation tracer [ 18 F]AV-1451. There was only sufficient data to conduct this group comparison with one tracer but these results show that despite the limitations of using [ 18 F]AV-1451, this tracer is still able to differentiate PSP from PD patients using tau binding values.…”

“…This off‐target binding could be the main reason for the trend observed with this tracer but there is also the issue of extensive SN degeneration in late‐stage PD patients 44,45 . Data for [ 18 F]PM‐PBB3 tracer binding to the SN was insufficient for the present model, but recent literature states that this tracer has mediated many of the off‐target binding issues observed with first‐generation tracers, including off‐target binding to the SN 46,47 …”

Human biodistribution and radiation dosimetry for the tau tracer [18F]Florzolotau in healthy subjects

“…In contrast, the tau pathology in non-AD patients with progressive supranuclear palsy (PSP) primarily exhibits the straight or distorted 4R tau isoform (Goedert et al 1992 ; Flament et al 1991 ; Saint-Aubert et al 2017 ). [ 18 F]Florzolotau has been proven capable of detecting both 3R tau and 4R tau isoforms (Ono et al 2017 ) and recent investigations have provided compelling evidence for the effectiveness of [ 18 F]Florzolotau in identifying tau pathologies in different types of neurodegenerative diseases, such as AD, CBD, PDD, and PSP (Tagai et al 2021 ; Li et al 2021 ; Miyamoto et al 2023 ; Liu et al 2023a , b ; Tang et al 2023 ).…”