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 K Wszolek, Makoto Higuchi, Vesna Sossi, A. Jon Stoessl

Research output: Contribution to journalArticle

21 Citations (Scopus)

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)
JournalMovement Disorders
DOIs
StateAccepted/In press - 2017

Fingerprint

tau Proteins
Parkinsonian Disorders
Putamen
Parietal Lobe
Mesencephalon
Thalamus
Merozoite Surface Protein 1
Tauopathies
Phenotype
alpha-Synuclein
Frontal Lobe
Temporal Lobe
Basal Ganglia
Positron-Emission Tomography
Primary Spontaneous Pneumothorax
Healthy Volunteers
2-(4-(6-(methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo(d)thiazol-6-ol
Pathology
Control Groups
Mutation

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Perez-Soriano, A., Arena, J. E., Dinelle, K., Miao, Q., Mckenzie, J., Neilson, N., ... Stoessl, A. J. (Accepted/In press). PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins. Movement Disorders. https://doi.org/10.1002/mds.27029

PBB3 imaging in Parkinsonian disorders : Evidence for binding to tau and other proteins. / Perez-Soriano, Alexandra; Arena, Julieta E.; Dinelle, Katie; Miao, Qing; Mckenzie, Jessamyn; Neilson, Nicole; Puschmann, Andreas; Schaffer, Paul; Shinotoh, Hitoshi; Smith-Forrester, Jenna; Shahinfard, Elham; Vafai, Nasim; Wile, Daryl; Wszolek, Zbigniew K; Higuchi, Makoto; Sossi, Vesna; Stoessl, A. Jon.

In: Movement Disorders, 2017.

Research output: Contribution to journalArticle

Perez-Soriano, A, Arena, JE, Dinelle, K, Miao, Q, Mckenzie, J, Neilson, N, Puschmann, A, Schaffer, P, Shinotoh, H, Smith-Forrester, J, Shahinfard, E, Vafai, N, Wile, D, Wszolek, ZK, Higuchi, M, Sossi, V & Stoessl, AJ 2017, 'PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins', Movement Disorders. https://doi.org/10.1002/mds.27029
Perez-Soriano, Alexandra ; Arena, Julieta E. ; Dinelle, Katie ; Miao, Qing ; Mckenzie, Jessamyn ; Neilson, Nicole ; Puschmann, Andreas ; Schaffer, Paul ; Shinotoh, Hitoshi ; Smith-Forrester, Jenna ; Shahinfard, Elham ; Vafai, Nasim ; Wile, Daryl ; Wszolek, Zbigniew K ; Higuchi, Makoto ; Sossi, Vesna ; Stoessl, A. Jon. / PBB3 imaging in Parkinsonian disorders : Evidence for binding to tau and other proteins. In: Movement Disorders. 2017.
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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.",
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T2 - Evidence for binding to tau and other proteins

AU - Perez-Soriano, Alexandra

AU - Arena, Julieta E.

AU - Dinelle, Katie

AU - Miao, Qing

AU - Mckenzie, Jessamyn

AU - Neilson, Nicole

AU - Puschmann, Andreas

AU - Schaffer, Paul

AU - Shinotoh, Hitoshi

AU - Smith-Forrester, Jenna

AU - Shahinfard, Elham

AU - Vafai, Nasim

AU - Wile, Daryl

AU - Wszolek, Zbigniew K

AU - Higuchi, Makoto

AU - Sossi, Vesna

AU - Stoessl, A. Jon

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - MSA

KW - PBB3

KW - PSP

KW - SNCA mutations

KW - Tau PET imaging

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