Universität zu Köln

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 ORCID: 0000-0002-5991-7812, Herms, Jochen, Yakushev, Igor and Rominger, Axel (2018). Comparison of F-18-T807 and F-18-THK5117 PET in a Mouse Mode of Tau Pathology. Front. Aging Neurosci., 10. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1663-4365

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Abstract

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 F-18-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). F-18-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. F-18-T807 was more sensitive than F-18-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brendel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Yousefi, Behrooz H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blume, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Herz, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Focke, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED Deussing, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Finn UNSPECIFIED UNSPECIFIED UNSPECIFIED Lindner, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED von Ungern-Sternberg, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartenstein, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Haass, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Okamura, Nobuyuki UNSPECIFIED orcid.org/0000-0002-5991-7812 UNSPECIFIED Herms, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Yakushev, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Rominger, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-183008
DOI:	10.3389/fnagi.2018.00174
Journal or Publication Title:	Front. Aging Neurosci.
Volume:	10
Date:	2018
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1663-4365
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-VIVO; ALZHEIMERS-DISEASE; ASTROCYTOSIS; F-18-AV-1451; DERIVATIVES; TRACER Multiple languages Geriatrics & Gerontology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18300