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

EJNMMI Research

Kelly P. Cosgrove¹  Nabeel Nabulsi¹  Ansel T. Hillmer¹  Richard E. Carson¹  Brian L. West²  Krista Fowles³  Daniel Holden³ 

[1] Department of Radiology and Biomedical Imaging, Yale University School of Medicine;Plexxikon Inc;Yale PET Center, Yale University School of Medicine;

关键词: Microglia;    Inflammation;    PET;    Imaging;    Immunology;   

DOI  :  10.1186/s13550-017-0305-0

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown