PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins

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PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins. / Perez-Soriano, Alexandra; Arena, Julieta E; Sossi, Vesna; Dinelle, Katie; Miao, Q.; McKenzie, Christine J.; Neilson, Nicole; Puschmann, A.; Schaffer, Paul; Shinotoh, Hitoshi; Smith-Forrester, Jenna; Shahinfard, Elham; Vafai, Nasim; Wile, Daryl; Wszolek, Z K; Higuchi, Makoto; Stoessl, A. J.

In: Movement Disorders, Vol. 32, No. Suppl 2, 01.06.2017, p. 585-587.

Research output: Contribution to journalPublished meeting abstract

Harvard

Perez-Soriano, A, Arena, JE, Sossi, V, Dinelle, K, Miao, Q, McKenzie, CJ, Neilson, N, Puschmann, A, Schaffer, P, Shinotoh, H, Smith-Forrester, J, Shahinfard, E, Vafai, N, Wile, D, Wszolek, ZK, Higuchi, M & Stoessl, AJ 2017, 'PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins', Movement Disorders, vol. 32, no. Suppl 2, pp. 585-587. https://doi.org/10.1002/mds.27087

APA

Perez-Soriano, A., Arena, J. E., Sossi, V., Dinelle, K., Miao, Q., McKenzie, C. J., Neilson, N., Puschmann, A., Schaffer, P., Shinotoh, H., Smith-Forrester, J., Shahinfard, E., Vafai, N., Wile, D., Wszolek, Z. K., Higuchi, M., & Stoessl, A. J. (2017). PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins. Movement Disorders, 32(Suppl 2), 585-587. https://doi.org/10.1002/mds.27087

CBE

Perez-Soriano A, Arena JE, Sossi V, Dinelle K, Miao Q, McKenzie CJ, Neilson N, Puschmann A, Schaffer P, Shinotoh H, Smith-Forrester J, Shahinfard E, Vafai N, Wile D, Wszolek ZK, Higuchi M, Stoessl AJ. 2017. PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins. Movement Disorders. 32(Suppl 2):585-587. https://doi.org/10.1002/mds.27087

MLA

Vancouver

Author

Perez-Soriano, Alexandra ; Arena, Julieta E ; Sossi, Vesna ; Dinelle, Katie ; Miao, Q. ; McKenzie, Christine J. ; Neilson, Nicole ; Puschmann, A. ; Schaffer, Paul ; Shinotoh, Hitoshi ; Smith-Forrester, Jenna ; Shahinfard, Elham ; Vafai, Nasim ; Wile, Daryl ; Wszolek, Z K ; Higuchi, Makoto ; Stoessl, A. J. / PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins. In: Movement Disorders. 2017 ; Vol. 32, No. Suppl 2. pp. 585-587.

RIS

TY - JOUR

T1 - PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins

AU - Perez-Soriano, Alexandra

AU - Arena, Julieta E

AU - Sossi, Vesna

AU - Dinelle, Katie

AU - Miao, Q.

AU - McKenzie, Christine J.

AU - Neilson, Nicole

AU - Puschmann, A.

AU - Schaffer, Paul

AU - Shinotoh, Hitoshi

AU - Smith-Forrester, Jenna

AU - Shahinfard, Elham

AU - Vafai, Nasim

AU - Wile, Daryl

AU - Wszolek, Z K

AU - Higuchi, Makoto

AU - Stoessl, A. J.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Objective: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 ([11C]methylamino pyridin-3-yl buta-1,3-dienyl benzo[d]thiazol-6-ol) in tauopathies, and in conditions not typically associated with tauopathy. Background: Tau imaging is a promising tool to study the link between tau and neurodegeneration. The specificity of tracers in vivo however remains uncertain, and off target binding is frequently present, limiting its use in parkinsonian disorders. Methods: Dynamic PET scans were obtained for 70 min after the bolus injection of [11C]PBB3 (mean dose 518.97MBq) in five PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype,3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 7 healthy controls of similar age. The occipital cortex was used as reference region for the PSP , the DCTN1 mutation and the MSA subjects. The cerebellar white matter was used as a reference region for the SNCA duplication carriers. Tissue reference Logan analysis was applied to each region of interest (ROI) using the appropriate reference region. Results: In PSP subjects, the highest retention of [11C]PBB3 was observed in putamen, midbrain, globus pallidus and substantia nigra. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. The DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and globus pallidus. In SNCA duplication carriers there was a significant increase of [11C] PBB3 binding compared to controls in globus pallidus, putamen, thalamus, ventral striatum, substantia nigra, and pedunculopontine nucleus. The MSA case showed increased binding in comparison to the control group in frontal lobe, globus pallidus, midbrain, parietal lobe, putamen, temporal lobe, substantia nigra, thalamus and ventral striatum. Conclusions: All PSP patients showed increased retention of the tracer in the basal ganglia, as clinically expected. However, binding was also present in asymptomatic SNCA duplication carriers as well as the subject with MSA, which are not typically associated with pathological tau deposition. This suggests the possibility that [11C]PBB3 binds to alpha-synuclein or other proteins involved in neurodegeneration.

AB - Objective: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 ([11C]methylamino pyridin-3-yl buta-1,3-dienyl benzo[d]thiazol-6-ol) in tauopathies, and in conditions not typically associated with tauopathy. Background: Tau imaging is a promising tool to study the link between tau and neurodegeneration. The specificity of tracers in vivo however remains uncertain, and off target binding is frequently present, limiting its use in parkinsonian disorders. Methods: Dynamic PET scans were obtained for 70 min after the bolus injection of [11C]PBB3 (mean dose 518.97MBq) in five PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype,3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 7 healthy controls of similar age. The occipital cortex was used as reference region for the PSP , the DCTN1 mutation and the MSA subjects. The cerebellar white matter was used as a reference region for the SNCA duplication carriers. Tissue reference Logan analysis was applied to each region of interest (ROI) using the appropriate reference region. Results: In PSP subjects, the highest retention of [11C]PBB3 was observed in putamen, midbrain, globus pallidus and substantia nigra. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. The DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and globus pallidus. In SNCA duplication carriers there was a significant increase of [11C] PBB3 binding compared to controls in globus pallidus, putamen, thalamus, ventral striatum, substantia nigra, and pedunculopontine nucleus. The MSA case showed increased binding in comparison to the control group in frontal lobe, globus pallidus, midbrain, parietal lobe, putamen, temporal lobe, substantia nigra, thalamus and ventral striatum. Conclusions: All PSP patients showed increased retention of the tracer in the basal ganglia, as clinically expected. However, binding was also present in asymptomatic SNCA duplication carriers as well as the subject with MSA, which are not typically associated with pathological tau deposition. This suggests the possibility that [11C]PBB3 binds to alpha-synuclein or other proteins involved in neurodegeneration.

KW - alpha synuclein

KW - endogenous compound

KW - tau protein

KW - tracer

KW - bolus injection

KW - chemical binding

KW - clinical article

KW - clinical trial

KW - control group

KW - controlled study

KW - disease carrier

KW - disease course

KW - female

KW - frontal lobe

KW - globus pallidus

KW - human

KW - human tissue

KW - imaging

KW - male

KW - mutation

KW - nerve degeneration

KW - occipital cortex

KW - parietal lobe

KW - parkinsonism

KW - pedunculopontine tegmental nucleus

KW - phenotype

KW - positron emission tomography

KW - putamen

KW - substantia nigra

KW - temporal lobe

KW - thalamus

KW - ventral striatum

KW - white matter

U2 - 10.1002/mds.27087

DO - 10.1002/mds.27087

M3 - Published meeting abstract

C2 - 28575549

VL - 32

SP - 585

EP - 587

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - Suppl 2

T2 - 21st International Congress of Parkinson's Disease and Movement Disorders

Y2 - 4 June 2017 through 8 June 2017

ER -