| Project/Area Number |
18K15608
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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 52040:Radiological sciences-related
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 糖尿病 / 膵β細胞 / GLUT2 / ストレプトゾトシン |
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| Outline of Final Research Achievements |
Pancreatic GLUT2 also plays an important role in the mechanism of glucose-stimulated insulin secretion. In this study, novel Fluorine-18-labeled streptozotocin (STZ) derivatives were synthesized to serve as glycoside analogs for in-vivo GLUT2 imaging. Fluorine was introduced to hexyl groups at the 3’-positions of the compounds. The synthesized compounds were more stable than STZ, and exhibited relatively good stability during purification in radiosynthesis. The compounds were then evaluated in PET imaging and ex-vivo biodistribution studies. As the results, high levels of radioactivity in the liver and kidney was observed within 5 minutes of administration. In contrast, the denitroso derivatives accumulated only in the kidney and bladder shortly after administration. Compounds with nitroso groups are thus expected to accumulate in GLUT2-expressing organs, and the presence of a nitroso group is essential for in-vivo GLUT2 imaging.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の放射性フッ素標識誘導体は、２型糖尿病の発症メカニズムに関連するGLUT2の発現組織である膵臓や肝臓、腸、腎臓に集積することが明らかにされた。また、本誘導体は糖骨格を有する構造であるが、既存の糖代謝分子プローブでGLUT1発現組織を描出する18F-FDGとは全く異なる体内分布を示した。したがって、本誘導体はGLUT2が関連する生命現象を非侵襲的に可視化する初めての分子イメージングプローブとして利用できる可能性が示唆された。そのため、本研究は2型糖尿病における膵臓や肝臓の糖取り込み能の臨床的変化を捉えられる放射性診断薬の開発へと発展できることが期待される。
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