PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins

Abstract

All PSP patients showed increased retention of the tracer in the basal ganglia, as expected. Binding was also present in asymptomatic SNCA duplication carriers and in an MSA case, which are not typically associated with pathological tau deposition. This suggests the possibility that [ C]PBB3 binds to alpha-synuclein. © 2017 International Parkinson and Movement Disorder Society.

Tau Imaging in Parkinsonism: What Have We Learned So Far?

“…40 One study using the [ 11 C]PBB3 ligand assessed a cohort of PSP-P patients. 41 Similar to the previously mentioned studies, they identified elevated tau uptake in the putamen, midbrain, and globus pallidus compared to controls. However, they did not identify any elevated uptake in dentate nucleus of the cerebellum or thalamus.…”

“…Similar patterns of uptake in globus pallidus and midbrain in PSP‐RS have been observed with [ 18 F]THK‐5351, with weaker evidence for cortical uptake . One study using the [ 11 C]PBB3 ligand assessed a cohort of PSP‐P patients . Similar to the previously mentioned studies, they identified elevated tau uptake in the putamen, midbrain, and globus pallidus compared to controls.…”

“…However, given that autoradiographic studies have convincingly demonstrated a lack of binding of [ 18 F]AV‐1451 to alpha‐synuclein in multiple system atrophy, the authors conclude that uptake likely reflects off‐target binding in this region. Tau‐PET imaging has also been reported using the [ 11 C]PBB3 ligand in one MSA‐P patient . This patient showed widespread increased uptake in the cortex and subcortical structures .…”

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

“…[11C]PBB3 PET also showed increased binding in cortical and subcortical regions in a patient with MSA (table 2). 59 Based on matched in vitro fluorescence and autoradiographic binding for PBB3 in the same brain regions, a subset of patients with MSA could be positive because of the high density of GCI in the putamen,60 even though the affinity of PBB3 to α-synuclein is 10–50 times less than that to tau 61. These tau ligands bind to β-pleated sheet secondary structures in tau filaments, which are also characterised by α-synuclein filaments.…”

PBB3 binding in a patient with corticobasal syndrome

“…11 C‐PBB3 in PSP showed specific binding in areas where the highest tau burden is expected and was higher in more advanced cases. However, binding was also observed in synucleinopathies, questioning its specificity for tau . In CBD, 11 C‐PBB3 may show specific binding that correlates with the clinical manifestations and asymmetric characteristics of CBS, but further studies are needed.…”