| Project/Area Number |
23K27555
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| Project/Area Number (Other) |
23H02864 (2023)
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2023) |
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| Section | 一般 |
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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
織内 昇 福島県立医科大学, 公私立大学の部局等, 教授 (40292586)
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| Co-Investigator(Kenkyū-buntansha) |
関亦 明子 福島県立医科大学, 看護学部, 教授 (50321823)
小島 祥敬 福島県立医科大学, 医学部, 教授 (60305539)
右近 直之 福島県立医科大学, 公私立大学の部局等, 講師 (70792985)
趙 松吉 福島県立医科大学, 公私立大学の部局等, 教授 (80374239)
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2025: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2024: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2023: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 核医学治療 / アスタチン211 / 唾液腺 / PSMA / 前立腺癌 / targeted α therapy / 211At-PSMA / radiation sialadenitis / salivary gland / SNARE proteins / prostate cancer / xerostomia |
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| Outline of Research at the Start |
The goal of this study is to elucidate the mechanism of salivary gland uptake of 211At-labeled compounds from a molecular perspective by clarifying the mechanism in relation to receptors such as the involvement of SNARE proteins, and to develop treatment for xerostomia.
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| Outline of Annual Research Achievements |
The goal of this study is to elucidate the mechanism of salivary gland uptake of 211At-labeled compounds from a molecular and pathological perspective, and to develop a treatment for xerostomia caused by salivary gland disorders.
By evaluating the specific uptake and off-target uptake of the 211At-PSMA ligand into the salivary glands of normal mice, we clarify the molecular mechanism of uptake in relation to receptors such as the involvement of SNARE proteins, and obtain knowledge that leads to the treatment of salivary gland disorders, including xerostomia and the relationship with taste disorders.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
The aim of the present study is to clarify the mechanism by which 211At-PSMA ligands accumulate in the salivary glands by elucidating a molecule involved in the transport of 211At-PSMA ligands in the salivary glands, and to develop a preventive method for radiation sialadenitis due to 211At-PSMA ligands therapy. We will quantitatively evaluate the specific uptake and off-target uptake of 211At-PSMA ligand into the salivary glands of normal mice and clarify the molecular mechanism of 211At-PSMA ligand uptake in relation to receptors such as the involvement of SNARE proteins and obtain knowledge that will lead to the treatment of salivary gland disorders.
We have established the study protocol of quantitative evaluation of specific and non-specific uptake of the 211At-PSMA ligand administered to normal mice by removal of salivary glands and pathological analysis to clarify the relationship between the absorbed dose of the salivary glands and pathological tissue damage and salivation. The relationship between the absorbed dose estimated from the accumulation of 211At-PSMA ligands and the amount of salivation will be clarified. Images of HE staining of the submandibular gland taken from mice treated with 211At-PSMA ligands with and without inhibition will be obtained to examine pathological contrast to the state of inflammation and the histological damage.
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| Strategy for Future Research Activity |
According to the protocol as described above, the animal study will be performed to identify molecules involved in receptor binding of 211At-PSMA ligands and confirm inhibition of uptake by knockdown of identified molecules, then obtain knowledge leading to the treatment of salivary gland dysfunction due to radiation sialadenitis.
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