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

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 [(11)C]PBR28 imaging paradigms for measuring dynamic microglia changes in Macaca mulatta. METHODS: Dynamic [(11)C]PBR28 PET imaging data with arterial blood sampling were acquired to quantify TSPO levels as [(11)C]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 [(11)C]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 [(11)C]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.