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Research ArticleBasic Science Investigation
Open Access

Short-Term Colony-Stimulating Factor 1 Receptor Inhibition–Induced Repopulation After Stroke Assessed by Longitudinal 18F-DPA-714 PET Imaging

Cristina Barca, Amanda J. Kiliaan, Lydia Wachsmuth, Claudia Foray, Sven Hermann, Cornelius Faber, Michael Schäfers, Maximilian Wiesmann, Bastian Zinnhardt and Andreas H. Jacobs
Journal of Nuclear Medicine September 2022, 63 (9) 1408-1414; DOI: https://doi.org/10.2967/jnumed.121.263004
Cristina Barca
1European Institute for Molecular Imaging, University of Münster, Münster, Germany;
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Amanda J. Kiliaan
2Department of Medical Imaging/Anatomy, Radboud University Medical Center, Radboud, The Netherlands;
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Lydia Wachsmuth
3Translational Research Imaging Center, University Hospital Münster, Münster, Germany;
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Claudia Foray
1European Institute for Molecular Imaging, University of Münster, Münster, Germany;
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Sven Hermann
1European Institute for Molecular Imaging, University of Münster, Münster, Germany;
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Cornelius Faber
3Translational Research Imaging Center, University Hospital Münster, Münster, Germany;
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Michael Schäfers
1European Institute for Molecular Imaging, University of Münster, Münster, Germany;
4Department of Nuclear Medicine, University Hospital Münster, Münster, Germany;
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Maximilian Wiesmann
2Department of Medical Imaging/Anatomy, Radboud University Medical Center, Radboud, The Netherlands;
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Bastian Zinnhardt
1European Institute for Molecular Imaging, University of Münster, Münster, Germany;
4Department of Nuclear Medicine, University Hospital Münster, Münster, Germany;
5Biomarkers and Translational Technologies, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and
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Andreas H. Jacobs
1European Institute for Molecular Imaging, University of Münster, Münster, Germany;
6Department of Geriatrics and Neurology, Johanniter Hospital, Bonn, Germany
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  • FIGURE 1.
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    FIGURE 1.

    Study design. IHC = immunohistochemistry; rt qPCR = real-time quantitative polymerase chain reaction; tMCAo = transient middle cerebral artery occlusion.

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    FIGURE 2.

    (A) Representative 18F-DPA-714 PET/CT images and corresponding T2-weighted MR images. (B) Quantification of mean 18F-DPA-714 uptake (percentage injected dose/mL) within infarct and contralateral striatum. (C) Infarct-to-contralateral striatum ratio. Treatment: ***P < 0.005. Day 7: ###P < 0.005. Day 30: &P < 0.05, &&&P < 0.005. %ID = percentage injected dose; T2w = T2-weighted.

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    FIGURE 3.

    Immunofluorescent staining for TSPO, CSF-1R, and CD68 in Iba-1–positive cell population in both control and PLX5622-treated mice on day 14 after ischemia. < = Iba-1–positive cell positive for marker; > = Iba-1–positive cell negative for marker; scale bar = 20 µm. DAPI = 4′,6-diamidino-2-phenylindole.

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    FIGURE 4.

    Gene expression of microglia- or macrophage-related markers on day 14 after ischemia. Treatment: *P < 0.05, **P < 0.01, ***P < 0.005. Contralateral hemisphere: #P < 0.05, ##P < 0.01, ###P < 0.005. mRNA = messenger RNA.

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    FIGURE 5.

    Behavioral tests: distance traveled (A), speed in open field (B), latency to fall during rotarod test (C), velocity during pole test (D), and forelimb strength as assessed with grip test (E). Treatment: *P < 0.05, **P < 0.01, ***P < 0.005. Baseline: #P < 0.05, ##P < 0.01, ###P < 0.005. Day 14: &P < 0.05.

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Journal of Nuclear Medicine: 63 (9)
Journal of Nuclear Medicine
Vol. 63, Issue 9
September 1, 2022
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Short-Term Colony-Stimulating Factor 1 Receptor Inhibition–Induced Repopulation After Stroke Assessed by Longitudinal 18F-DPA-714 PET Imaging
Cristina Barca, Amanda J. Kiliaan, Lydia Wachsmuth, Claudia Foray, Sven Hermann, Cornelius Faber, Michael Schäfers, Maximilian Wiesmann, Bastian Zinnhardt, Andreas H. Jacobs
Journal of Nuclear Medicine Sep 2022, 63 (9) 1408-1414; DOI: 10.2967/jnumed.121.263004

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Short-Term Colony-Stimulating Factor 1 Receptor Inhibition–Induced Repopulation After Stroke Assessed by Longitudinal 18F-DPA-714 PET Imaging
Cristina Barca, Amanda J. Kiliaan, Lydia Wachsmuth, Claudia Foray, Sven Hermann, Cornelius Faber, Michael Schäfers, Maximilian Wiesmann, Bastian Zinnhardt, Andreas H. Jacobs
Journal of Nuclear Medicine Sep 2022, 63 (9) 1408-1414; DOI: 10.2967/jnumed.121.263004
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Keywords

  • colony-stimulating factor 1 receptor
  • microglia
  • stroke
  • 18F-DPA-714
  • repopulation
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