Development of gadolinium neutron capture therapy agent for next-generation radiation therapy applied for bone cancer
Project/Area Number |
19K07717
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Juntendo University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 中性子補足療法 / ガドリニウム / LA-ICP-MS / 中性子捕捉療法 / 骨転移腫瘍 / 骨腫瘍 / 動物モデル |
Outline of Research at the Start |
担骨腫瘍モデル動物を用いて、157Gd-EDTMPの骨腫瘍への集積をin vivoで検証する。小動物を用いた骨腫瘍には、腫瘍の種類により様々なモデルがある。本研究ではモデルが作成しやすく扱いやすいマウスの各骨腫瘍モデルを作成する。腫瘍長径が一定の大きさになったあと。Gd-EDTMP製剤(5-100 mg Gd/kg)を腹腔内投与し、投与6または24時間後に採血し、骨、腫瘍組織、ほか各種組織を摘出する。血中および各種組織のGd濃度を測定するとともに、腫瘍組織と正常骨組織および周辺筋肉組織のGdについてはLA-ICP-MS法により二次元イメージングを行い腫瘍/正常組織比を算出する。
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Outline of Final Research Achievements |
In this study, we evaluated the tissue distribution and efficacy of Gd-tetra(methylenephosphonic acid) chelate (Gd-EDTMP) as a neutron capture therapy agent. We proceeded with the same study by creating a carcinogenesis model in elderly mice with a closed epiphyseal line. After neutron irradiation, the distribution of 157Gd in and around the bone was analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). 20 mg/kg of Gd-EDTMP administered intraperitoneally resulted in a Gd concentration of 1000-2000 ppm in the bone 24 hours later The results of this study showed that the Gd concentration in the bone was 1000-2000 ppm. In addition, a tumor shrinking effect of neutron irradiation was observed in a mouse model of bone metastasis of a 4T1 mammary tumor, although it was not statistically significant.
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Academic Significance and Societal Importance of the Research Achievements |
治療に適した腫瘍抑制効果を得るためには、Gdを腫瘍領域でさらに濃縮する必要があることが示唆された。本研究で観察されたような、4T1細胞自体へのGdの蓄積メカニズムの解析が不可欠である。また、より効率的な投与方法を模索することが、治療成績の向上につながると考えられます。
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Report
(5 results)
Research Products
(15 results)
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[Presentation] Tumor growth suppression by gadolinium-neutron capture therapy with intra-tumoral injection of gadolinium-liposome complex (Gd-plex) to pancreatic cancer model in vivo.2021
Author(s)
Yanagie Y., Yanagie H., Hou X., Yanagawa M., Matsukawa T., Kubota A., Suzuki M., Masunaga S., Sakurai Y., Tanaka H., Nashimoto M., Takahashi H.
Organizer
The 19th International Congress on Neutron Capture Therapy (ICNCT 19),
Related Report
Int'l Joint Research
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[Presentation] Application of intra-tumoral injection of cationic polymers mixed with Gd compounds for Neutron Capture therapy to pancreatic cancer model2021
Author(s)
Yanagie H., Yanagawa M., Hou X., Yanagie Y., Matsukawa T., Kubota A., Suzuki M., Masunaga S., Sakurai Y., Tanaka H., Nashimoto M., Takahashi H
Organizer
The 19th International Congress on Neutron Capture Therapy (ICNCT 19),
Related Report
Int'l Joint Research
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