Abstract
BackgroundThe 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.MethodsDynamic [11C]PBR28 PET imaging data with arterial blood sampling were acquired to quantify TSPO levels as [11C]PBR28 VT. Scans were acquired at three timepoints: baseline, immediately post-drug, and prolonged post-drug.ResultsIn one animal, a colony-stimulating factor 1 receptor kinase inhibitor, previously shown to deplete brain microglia, reduced [11C]PBR28 VT 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 VT in brain by 39 ± 9% from baseline, which recovered after 14 days to −11 ± 3% from baseline.ConclusionsThese studies provide preliminary evidence of complementary paradigms to assess microglia dynamics via in vivo TSPO imaging.
Highlights
The 18-kDa translocator protein (TSPO) is an important target for assessing neuroimmune function in brain with positron-emission tomography (PET) imaging
Following 8 days of PLX3397 intake (7 days of food plus the oral gavage), which resulted in blood levels of 2.06 μg/mL PLX3397, [11C]PBR28 volumes of distribution (VT) was reduced by 46 ± 3% compared to baseline values (Table 1)
These data demonstrate the potential for two complementary imaging paradigms that assay dynamic changes in TSPO levels in vivo
Summary
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 VT. Scans were acquired at three timepoints: baseline, immediately post-drug, and prolonged post-drug. The immune system in the central nervous system is critical to maintaining homeostasis in the brain. Imbalances in the brain’s immune system are linked to a variety of neurological pathologies [1]. Microglia are resident macrophages in the central nervous system that function as critical regulators of neuroimmune function. Pharmaceutical therapeutics targeting microglia are of high interest to regulate
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
