Development of gadolinium neutron capture therapy agent for next-generation radiation therapy applied for bone cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07717
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Juntendo University
• Principal Investigator: Matsukawa Takehisa 順天堂大学, 医学部, 准教授 (60453586)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 中性子補足療法 / ガドリニウム / LA-ICP-MS

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.

Free Research Field

薬物動態学

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。