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

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.

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