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

• Published in: Movement disorders Vol. 32; no. 7; pp. 1016 - 1024
• Main Authors: 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, Higuchi, Makoto, Sossi, Vesna, Stoessl, A. Jon
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2017
• Subjects: Aged; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Basal ganglia; Basal Ganglia - diagnostic imaging; Basal Ganglia - metabolism; Benzothiazoles; Brain diseases; Carbon Radioisotopes; Central nervous system diseases; Cerebellum; Clinical Medicine; Dynactin Complex - genetics; Frontal lobe; Humans; Image processing; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Mesencephalon; Middle Aged; Movement disorders; MSA; Multiple System Atrophy - diagnostic imaging; Multiple System Atrophy - metabolism; Neostriatum; Neurodegenerative diseases; Neurologi; Neurology; Nuclei; Parietal lobe; Parkinsonian Disorders - diagnostic imaging; Parkinsonian Disorders - metabolism; PBB3; Pedunculopontine tegmental nucleus; Positron-Emission Tomography - methods; PSP; Putamen; SNCA mutations; Substantia alba; Supranuclear Palsy, Progressive - diagnostic imaging; Supranuclear Palsy, Progressive - metabolism; Synuclein; Tau PET imaging; Tau protein; tau Proteins - metabolism; Temporal lobe; Thalamus; SNCA mutations; MSA; PSP; Tau PET imaging; PBB3
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.27029

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. © 2017 International Parkinson and Movement Disorder Society