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

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

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.