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

Microglial depletion and activation: A [(11)C]PBR28 PET study in nonhuman primates.
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DOI:
10.1186/s13550-017-0305-0
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发表时间:
2017-12
期刊:
影响因子:
3.2
通讯作者:
Cosgrove KP
Cosgrove KP
中科院分区:
医学3区
文献类型:
--
作者:
Hillmer AT;Holden D;Fowles K;Nabulsi N;West BL;Carson RE;Cosgrove KP

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