| Project/Area Number |
18KK0439
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Mukogawa Women's University (2020-2022)
Nagasaki University (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2019 – 2022
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
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| Keywords | 内用放射線治療薬剤 / ナノキャリア / 細胞内動態 / トリプルネガティブ乳がん / ナノ / フルオロ / フルオロカーボン / トリプルネガティブ乳癌 |
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| Outline of Final Research Achievements |
Triple negative breast cancer (TNBC) is a high malignancy caner with poor prognosis, and currently no effective treatment has been established. In this study, we focused on the enhancement of ultrasound gas solubility by fluorocarbons and radioactivity by heat generation after ultrasound irradiation, and developed an internal radiation therapy drug with both in intracellular kinetic control and antitumor effects. Fluorinated peptide lipids were synthesized and bubble formulations were prepared, and their efficacy was clarified by physicochemical evaluation. In addition, we synthesized a radiolabeled NQO1 target compound with improved metabolic stability. In the future, we will prepare a radiopharmaceutical encapsulating the developed radiopharmaceutical and verify its intracellular kinetics and therapeutic efficacy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、明確な治療方法が確立されていないトリプルネガティブ乳がん(TNBC)に対する内用放射線治療薬剤の開発を目的に、NQO1標的放射性薬剤を細胞内動態制御と抗腫瘍効果が期待できる超音波応答性フッ素化バブルに内包した薬剤の開発を目的に研究を行った。フッ素基の導入により、フッ素化脂質分子同士および表音波造影ガスとの間でフルオラス相互が生じ膜が安定化することが明らかとなった。また、代謝安定を向上したNQO1標的放射性ヨウ素標識体の合成に成功した。今後、NQO1特異的放射性薬剤を内包したEVQ修飾フッ素化ペプチド脂質によるバブル製剤の内用放射線治療薬剤としての有用性を評価していく。
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