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EJNMMI Res. 2017 Dec;7(1):59. doi: 10.1186/s13550-017-0305-0. Epub 2017 Jul 24.

Microglial depletion and activation: A [11C]PBR28 PET study in nonhuman primates.

Author information

1
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, 06520, USA. ansel.hillmer@yale.edu.
2
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. ansel.hillmer@yale.edu.
3
Yale PET Center, Yale University School of Medicine, New Haven, CT, USA. ansel.hillmer@yale.edu.
4
Yale PET Center, Yale University School of Medicine, New Haven, CT, USA.
5
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, 06520, USA.
6
Plexxikon Inc, Berkeley, CA, USA.
7
Department of Biomedical Engineering, Yale University School of Medicine, New Haven, CT, USA.
8
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
9
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.

Abstract

BACKGROUND:

The 18-kDa translocator protein (TSPO) is an important target for assessing neuroimmune function in brain with positron-emission tomography (PET) imaging. The goal of this work was to assess two [11C]PBR28 imaging paradigms for measuring dynamic microglia changes in Macaca mulatta.

METHODS:

Dynamic [11C]PBR28 PET imaging data with arterial blood sampling were acquired to quantify TSPO levels as [11C]PBR28 V T. Scans were acquired at three timepoints: baseline, immediately post-drug, and prolonged post-drug.

RESULTS:

In one animal, a colony-stimulating factor 1 receptor kinase inhibitor, previously shown to deplete brain microglia, reduced [11C]PBR28 V T in brain by 46 ± 3% from baseline, which recovered after 12 days to 7 ± 5% from baseline. In a different animal, acute lipopolysaccharide administration, shown to activate brain microglia, increased [11C]PBR28 V T in brain by 39 ± 9% from baseline, which recovered after 14 days to -11 ± 3% from baseline.

CONCLUSIONS:

These studies provide preliminary evidence of complementary paradigms to assess microglia dynamics via in vivo TSPO imaging.

KEYWORDS:

Imaging; Immunology; Inflammation; Microglia; PET

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