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

Alexandra Perez-Soriano, Julieta E. Arena, Katie Dinelle, Qing Miao, Jessamyn McKenzie, Nicole Neilson, Andreas Puschmann, Paul Schaffer, Hitoshi Shinotoh, Jenna Smith-Forrester, Elham Shahinfard, Nasim Vafai, Daryl Wile, Zbigniew Wszolek, Makoto Higuchi, Vesna Sossi, A. Jon Stoessl

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Background and Objectives: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy. Methods: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [11C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region. Results: In comparison to the control group, PSP subjects showed specific uptake of [11C]PBB3 in putamen, midbrain, GP, and SN. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. A DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and GP. In SNCA duplication carriers, there was a significant increase of [11C] PBB3 binding in GP, putamen, thalamus, ventral striatum, SN, and pedunculopontine nucleus. The MSA case showed increased binding in frontal lobe, GP, midbrain, parietal lobe, putamen, temporal lobe, SN, thalamus, and ventral striatum. Conclusions: 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 [11C]PBB3 binds to alpha-synuclein.

Original languageEnglish (US)
Pages (from-to)1016-1024
Number of pages9
JournalMovement Disorders
Volume32
Issue number7
DOIs
StatePublished - Jul 2017

Keywords

  • MSA
  • PBB3
  • PSP
  • SNCA mutations
  • Tau PET imaging

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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