Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology

Positron-emission-tomography (PET) imaging of tau pathology has facilitated development of anti-tau therapies. While members of the arylquinoline and pyridoindole families have been the most frequently used tau radioligands so far, analyses of their comparative performance in vivo are scantly docume...

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Autores principales: Brendel, Matthias, Yousefi, Behrooz H., Blume, Tanja, Herz, Michael, Focke, Carola, Deussing, Maximilian, Peters, Finn, Lindner, Simon, von Ungern-Sternberg, Barbara, Drzezga, Alexander, Bartenstein, Peter, Haass, Christian, Okamura, Nobuyuki, Herms, Jochen, Yakushev, Igor, Rominger, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999706/
https://www.ncbi.nlm.nih.gov/pubmed/29930508
http://dx.doi.org/10.3389/fnagi.2018.00174
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author Brendel, Matthias
Yousefi, Behrooz H.
Blume, Tanja
Herz, Michael
Focke, Carola
Deussing, Maximilian
Peters, Finn
Lindner, Simon
von Ungern-Sternberg, Barbara
Drzezga, Alexander
Bartenstein, Peter
Haass, Christian
Okamura, Nobuyuki
Herms, Jochen
Yakushev, Igor
Rominger, Axel
author_facet Brendel, Matthias
Yousefi, Behrooz H.
Blume, Tanja
Herz, Michael
Focke, Carola
Deussing, Maximilian
Peters, Finn
Lindner, Simon
von Ungern-Sternberg, Barbara
Drzezga, Alexander
Bartenstein, Peter
Haass, Christian
Okamura, Nobuyuki
Herms, Jochen
Yakushev, Igor
Rominger, Axel
author_sort Brendel, Matthias
collection PubMed
description Positron-emission-tomography (PET) imaging of tau pathology has facilitated development of anti-tau therapies. While members of the arylquinoline and pyridoindole families have been the most frequently used tau radioligands so far, analyses of their comparative performance in vivo are scantly documented. Here, we conducted a head-to-head PET comparison of the arylquinoline (18)FT807 and the pyridoindole (18)FTHK5117 PET in a mouse model of tau pathology. PET recordings were obtained in groups of (N = 5–7) P301S and wild-type (WT) mice at 6 and 9 months of age. Volume-of-interest based analysis (standard-uptake-value ratio, SUVR) was used to calculate effect sizes (Cohen’s d) for each tracer and age. Statistical parametric mapping (SPM) was used to assess regional similarity (dice coefficient) of tracer binding alterations for the two tracers. Immunohistochemistry staining of neurofibrillary tangles was performed for validation ex vivo. Significantly elevated (18)F-T807 binding in the brainstem of P301S mice was already evident at 6 months (+14%, p < 0.01, d = 1.64), and increased further at 9 months (+23%, p < 0.001, d = 2.70). (18)F-THK5117 indicated weaker increases and effect sizes at 6 months (+5%, p < 0.05, d = 1.07) and 9 months (+10%, p < 0.001, d = 1.49). Regional similarity of binding of the two tracers was high (71%) at 9 months. (18)F-T807 was more sensitive than (18)F-THK5117 to tau pathology in this model, although both tracers present certain obstacles, which need to be considered in the design of longitudinal preclinical tau imaging studies.
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spelling pubmed-59997062018-06-21 Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology Brendel, Matthias Yousefi, Behrooz H. Blume, Tanja Herz, Michael Focke, Carola Deussing, Maximilian Peters, Finn Lindner, Simon von Ungern-Sternberg, Barbara Drzezga, Alexander Bartenstein, Peter Haass, Christian Okamura, Nobuyuki Herms, Jochen Yakushev, Igor Rominger, Axel Front Aging Neurosci Neuroscience Positron-emission-tomography (PET) imaging of tau pathology has facilitated development of anti-tau therapies. While members of the arylquinoline and pyridoindole families have been the most frequently used tau radioligands so far, analyses of their comparative performance in vivo are scantly documented. Here, we conducted a head-to-head PET comparison of the arylquinoline (18)FT807 and the pyridoindole (18)FTHK5117 PET in a mouse model of tau pathology. PET recordings were obtained in groups of (N = 5–7) P301S and wild-type (WT) mice at 6 and 9 months of age. Volume-of-interest based analysis (standard-uptake-value ratio, SUVR) was used to calculate effect sizes (Cohen’s d) for each tracer and age. Statistical parametric mapping (SPM) was used to assess regional similarity (dice coefficient) of tracer binding alterations for the two tracers. Immunohistochemistry staining of neurofibrillary tangles was performed for validation ex vivo. Significantly elevated (18)F-T807 binding in the brainstem of P301S mice was already evident at 6 months (+14%, p < 0.01, d = 1.64), and increased further at 9 months (+23%, p < 0.001, d = 2.70). (18)F-THK5117 indicated weaker increases and effect sizes at 6 months (+5%, p < 0.05, d = 1.07) and 9 months (+10%, p < 0.001, d = 1.49). Regional similarity of binding of the two tracers was high (71%) at 9 months. (18)F-T807 was more sensitive than (18)F-THK5117 to tau pathology in this model, although both tracers present certain obstacles, which need to be considered in the design of longitudinal preclinical tau imaging studies. Frontiers Media S.A. 2018-06-07 /pmc/articles/PMC5999706/ /pubmed/29930508 http://dx.doi.org/10.3389/fnagi.2018.00174 Text en Copyright © 2018 Brendel, Yousefi, Blume, Herz, Focke, Deussing, Peters, Lindner, von Ungern-Sternberg, Drzezga, Bartenstein, Haass, Okamura, Herms, Yakushev and Rominger. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Brendel, Matthias
Yousefi, Behrooz H.
Blume, Tanja
Herz, Michael
Focke, Carola
Deussing, Maximilian
Peters, Finn
Lindner, Simon
von Ungern-Sternberg, Barbara
Drzezga, Alexander
Bartenstein, Peter
Haass, Christian
Okamura, Nobuyuki
Herms, Jochen
Yakushev, Igor
Rominger, Axel
Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology
title Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology
title_full Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology
title_fullStr Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology
title_full_unstemmed Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology
title_short Comparison of (18)F-T807 and (18)F-THK5117 PET in a Mouse Model of Tau Pathology
title_sort comparison of (18)f-t807 and (18)f-thk5117 pet in a mouse model of tau pathology
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999706/
https://www.ncbi.nlm.nih.gov/pubmed/29930508
http://dx.doi.org/10.3389/fnagi.2018.00174
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