| Project/Area Number |
16K10302
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | National Institutes for Quantum and Radiological Science and Technology |
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Principal Investigator |
Okamura Toshimitsu 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 標識薬剤開発部, 研究員(任常) (80443068)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | PET / NOX / 酸化 / NADPHオキシダーゼ |
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| Outline of Final Research Achievements |
The purpose of this study was to investigate the feasibility of measuring the activity of NADPH oxidase (NOX) in the brain using an NADPH analog ([11C]DHQ1) for positron emission tomography. The previous study showed that [11C]DHQ1 has the following properties: blood-brain barrier permeability and enzymatic oxidation to the hydrophilic metabolite in the brain. In this study, the oxidation was inhibited by several NOX inhibitors, suggesting that NOX might contribute to the oxidation of [11C]DHQ1. However, there was not a significant difference in the brain kinetics of [11C]DHQ1 between NOX knockout mice and wild-type mice, showing that NOX would not contribute to the oxidation of [11C]DHQ1 in the brain. Thus, further chemical modifications of [11C]DHQ1 will be needed for NOX imaging, while [11C]DHQ1 could be used as a tracer for imaging the activity of cytochrome P450 (CYP) in the brain because the oxidation of [11C]DHQ1 was blocked by (CYP) inhibitors.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、当初目的としたNOX活性測定用トレーサの開発までは至らなかったが、提案した測定原理でNOX活性測定は可能であり、今後トレーサを再設計し、NOXトレーサを見出す予定である。一方で、本課題で評価したNADPH類似体の[11C]DHQ1については、脳内のチトクロームP450(CYP)活性イメージングトレーサとしての可能性が見出された。NOXやCYPは病態生理学的に重要な役割を果たしており、これらの酵素活性を非侵襲的に測定することは、様々な脳疾患の発症機構の解明や早期診断、さらにはその治療法の開発につながることが期待される。
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