Cortical [¹⁸F]PI‐2620 Binding Differentiates Corticobasal Syndrome Subtypes

Abstract

Background Corticobasal syndrome is associated with cerebral protein aggregates composed of 4‐repeat (~50% of cases) or mixed 3‐repeat/4‐repeat tau isoforms (~25% of cases) or nontauopathies (~25% of cases). Objectives The aim of this single‐center study was to investigate the diagnostic value of the tau PET‐ligand [18F]PI‐2620 in patients with corticobasal syndrome. Methods Forty‐five patients (71.5 ± 7.6 years) with corticobasal syndrome and 14 age‐matched healthy controls underwent [18F]PI‐2620‐PET. Beta‐amyloid status was determined by cerebral β‐amyloid PET and/or CSF analysis. Subcortical and cortical [18F]PI‐2620 binding was quantitatively and visually compared between β‐amyloid‐positive and ‐negative patients and controls. Regional [18F]PI‐2620 binding was correlated with clinical and demographic data. Results Twenty‐four percent (11 of 45) were β‐amyloid‐positive. Significantly elevated [18F]PI‐2620 distribution volume ratios were observed in both β‐amyloid‐positive and β‐amyloid‐negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [18F]PI‐2620 PET positivity was distinctly higher in β‐amyloid‐positive compared with β‐amyloid‐negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [18F]PI‐2620 PET revealed a sensitivity of 91% for β‐amyloid‐positive and of 65% for β‐amyloid‐negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of β‐amyloid status, hemispheric lateralization of [18F]PI‐2620 signal reflected contralateral predominance of clinical disease severity. Conclusions Our data indicate a value of [18F]PI‐2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in β‐amyloid‐positive as well as β‐amyloid‐negative corticobasal syndrome. In corticobasal syndrome, [18F]PI‐2620 may potentially serve for a differential diagnosis and for monitoring disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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

“…The 18 F‐florzolotau PET findings presented herein also support an increased tracer uptake in subcortical regions of patients with CBS—a pattern with similarities to PSP 9 . On analyzing 18 F‐PI‐2620 signals in patients with CBS and PSP‐RS, Palleis and colleagues 8 reported distinct findings for the two conditions—with the former being characterized by an increased tracer uptake in the putamen and external GP and the latter in the internal GP, STN, and substantia nigra. However, our observations did not show obvious differences in terms of positivity or negativity ratios but were limited to quantitative analysis.…”

[11C]PBB3 binding in Aβ(–) or Aβ(+) corticobasal syndrome

“…CBS patients (Palleis et al, 2021). In that study, a clear hemispheric asymmetry was observed in binding and correlated well with symptom dominant side.…”

Assessment of perfusion deficit with early phases of [18F]PI-2620 tau-PET versus [18F]flutemetamol-amyloid-PET recordings

“…Patients with 4R-tauopathies (PSP and CBS) were assessed by the PSP rating scale. Tau-PET analysis and separate analysis of early-phase imaging of both tracers were reported in previous investigations [ 9 , 13 , 23 – 25 ]. The control cohort ( n = 15) was selected from previous studies [ 13 , 23 ].…”

“…Tau-PET analysis and separate analysis of early-phase imaging of both tracers were reported in previous investigations [ 9 , 13 , 23 – 25 ]. The control cohort ( n = 15) was selected from previous studies [ 13 , 23 ]. All controls had negative amyloid- and tau-PET scans (visual read) and a Fazekas score ≤ 1.…”

“…An orienting sample size estimation (explained σ/residual σ = 1; α = 0.05; G*Power V3.1.9.2) indicated a necessary sample size of n = 16 to detect associations between the early-phase of [ 18 F]flutemetamol and early-phase of [ 18 F]PI-2620 with a statistical power of 0.95. PET imaging was either performed during the clinical workup or part of the screening/imaging of a prospective observational cohort study [ 12 , 13 ]. Informed written consent was obtained according to the Declaration of Helsinki.…”