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Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy
IMPORTANCE: Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. OBJECTIVE: To i...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341407/ https://www.ncbi.nlm.nih.gov/pubmed/33165511 http://dx.doi.org/10.1001/jamaneurol.2020.2526 |
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author | Brendel, Matthias Barthel, Henryk van Eimeren, Thilo Marek, Ken Beyer, Leonie Song, Mengmeng Palleis, Carla Gehmeyr, Mona Fietzek, Urban Respondek, Gesine Sauerbeck, Julia Nitschmann, Alexander Zach, Christian Hammes, Jochen Barbe, Michael T. Onur, Oezguer Jessen, Frank Saur, Dorothee Schroeter, Matthias L. Rumpf, Jost-Julian Rullmann, Michael Schildan, Andreas Patt, Marianne Neumaier, Bernd Barret, Olivier Madonia, Jennifer Russell, David S. Stephens, Andrew Roeber, Sigrun Herms, Jochen Bötzel, Kai Classen, Joseph Bartenstein, Peter Villemagne, Victor Levin, Johannes Höglinger, Günter U. Drzezga, Alexander Seibyl, John Sabri, Osama |
author_facet | Brendel, Matthias Barthel, Henryk van Eimeren, Thilo Marek, Ken Beyer, Leonie Song, Mengmeng Palleis, Carla Gehmeyr, Mona Fietzek, Urban Respondek, Gesine Sauerbeck, Julia Nitschmann, Alexander Zach, Christian Hammes, Jochen Barbe, Michael T. Onur, Oezguer Jessen, Frank Saur, Dorothee Schroeter, Matthias L. Rumpf, Jost-Julian Rullmann, Michael Schildan, Andreas Patt, Marianne Neumaier, Bernd Barret, Olivier Madonia, Jennifer Russell, David S. Stephens, Andrew Roeber, Sigrun Herms, Jochen Bötzel, Kai Classen, Joseph Bartenstein, Peter Villemagne, Victor Levin, Johannes Höglinger, Günter U. Drzezga, Alexander Seibyl, John Sabri, Osama |
author_sort | Brendel, Matthias |
collection | PubMed |
description | IMPORTANCE: Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. OBJECTIVE: To investigate the potential of the novel tau radiotracer (18)F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants underwent dynamic (18)F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP–non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. MAIN OUTCOMES AND MEASURES: Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, (18)F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. RESULTS: Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP–non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable (18)F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with (18)F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP–non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. CONCLUSIONS AND RELEVANCE: This multicenter evaluation indicates a value of (18)F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP. |
format | Online Article Text |
id | pubmed-7341407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-73414072020-07-09 Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy Brendel, Matthias Barthel, Henryk van Eimeren, Thilo Marek, Ken Beyer, Leonie Song, Mengmeng Palleis, Carla Gehmeyr, Mona Fietzek, Urban Respondek, Gesine Sauerbeck, Julia Nitschmann, Alexander Zach, Christian Hammes, Jochen Barbe, Michael T. Onur, Oezguer Jessen, Frank Saur, Dorothee Schroeter, Matthias L. Rumpf, Jost-Julian Rullmann, Michael Schildan, Andreas Patt, Marianne Neumaier, Bernd Barret, Olivier Madonia, Jennifer Russell, David S. Stephens, Andrew Roeber, Sigrun Herms, Jochen Bötzel, Kai Classen, Joseph Bartenstein, Peter Villemagne, Victor Levin, Johannes Höglinger, Günter U. Drzezga, Alexander Seibyl, John Sabri, Osama JAMA Neurol Original Investigation IMPORTANCE: Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. OBJECTIVE: To investigate the potential of the novel tau radiotracer (18)F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants underwent dynamic (18)F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP–non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. MAIN OUTCOMES AND MEASURES: Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, (18)F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. RESULTS: Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP–non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable (18)F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with (18)F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP–non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. CONCLUSIONS AND RELEVANCE: This multicenter evaluation indicates a value of (18)F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP. American Medical Association 2020-11 2020-07-07 /pmc/articles/PMC7341407/ /pubmed/33165511 http://dx.doi.org/10.1001/jamaneurol.2020.2526 Text en Copyright 2020 Brendel M et al. JAMA Neurology. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation Brendel, Matthias Barthel, Henryk van Eimeren, Thilo Marek, Ken Beyer, Leonie Song, Mengmeng Palleis, Carla Gehmeyr, Mona Fietzek, Urban Respondek, Gesine Sauerbeck, Julia Nitschmann, Alexander Zach, Christian Hammes, Jochen Barbe, Michael T. Onur, Oezguer Jessen, Frank Saur, Dorothee Schroeter, Matthias L. Rumpf, Jost-Julian Rullmann, Michael Schildan, Andreas Patt, Marianne Neumaier, Bernd Barret, Olivier Madonia, Jennifer Russell, David S. Stephens, Andrew Roeber, Sigrun Herms, Jochen Bötzel, Kai Classen, Joseph Bartenstein, Peter Villemagne, Victor Levin, Johannes Höglinger, Günter U. Drzezga, Alexander Seibyl, John Sabri, Osama Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy |
title | Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy |
title_full | Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy |
title_fullStr | Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy |
title_full_unstemmed | Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy |
title_short | Assessment of (18)F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy |
title_sort | assessment of (18)f-pi-2620 as a biomarker in progressive supranuclear palsy |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341407/ https://www.ncbi.nlm.nih.gov/pubmed/33165511 http://dx.doi.org/10.1001/jamaneurol.2020.2526 |
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