| Project/Area Number |
19K16274
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | National Institutes for Quantum and Radiological Science and Technology |
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Principal Investigator |
Zhou Xiaoyun 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 博士研究員(任常) (40834099)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | PET / CSF1R / P2X7R / MAGL / Neuroinflammation / Mice |
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| Outline of Research at the Start |
The study seeks to identify new in vivo imaging biomarkers for inflamed brain. We will develop PET-radioligands targeting three important molecules involving in CNS inflammatory processes-MAGL, CSF1R, and P2X7R and characterize these target molecules in animal models of CNS inflammation.
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| Outline of Final Research Achievements |
PET imaging of MAGL, P2X7R, and CSF1R, molecules involving in microgliosis and inflammatory processes has been carried out in mouse models of acute and chronic neuroinflammation. We have found an increased P2X7R and CSF1R radioligands retention in inflammatory brain regions. Furthermore, the pharmacokinetics of 11C-GW2580, a novel tracer for CSF1R has been quantified and compared with that of a reported CSF1R radioligand in mice and monkeys. The study demonstrated that 11C-GW2580 enables detection of microglial activation with higher sensitivity than the reported CSF1R tracer. Our findings suggest the feasibility of P2X7R- and CSF1R-PET for imaging of reactive microglia in diverse neuroinflammatory diseases. MAGL-PET was applied to determine the dose and regimen of an MAGL inhibitor by estimating the time-course occupancy of MAGL after drug administration. With the optimal treatment plan, the therapeutic potential of MAGL inhibition in a mouse model of tauopathy was investigated.
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| Academic Significance and Societal Importance of the Research Achievements |
This work has validated CSF1R and P2X7R as PET imaging biomarkers for microgliosis, allowing us to not only study the pathophysiological roles of those receptors in brain disorders, but also to explore neuroinflammatory processes from different angles.
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