Dynamic Imaging of LDH Inhibition in Tumors by 13C-MRI to Treat Colon Cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto University
• Principal Investigator: OSHIMA NOBU 京都大学, 医学研究科, 客員研究員 (70571454)
• Co-Investigator(Kenkyū-buntansha): 兵藤 文紀 岐阜大学, 大学院医学系研究科, 特任准教授 (10380693) ; 久森 重夫 京都大学, 医学研究科, 助教 (50534351) ; 板谷 喜朗 京都大学, 医学研究科, 助教 (80814029)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / 癌代謝 / LDH / LDH阻害薬 / 超偏極13C-MRI

Outline of Final Research Achievements

Pyruvate metabolism involves two major pathways, the "glycolytic" and the "OxPhos" pathways. Colon cancer cells also showed enhanced pyruvate metabolism in response to high energy demand, but the balance between the "glycolytic" and "OxPhos" pathways in the cells was different in each cell line. And, it was also revealed that there was metabolic plasticity between the two pathways. The response to each metabolic pathway inhibitor was also different in each cell line, and the anti-tumor effect obtained was also different.
In this study, we used a novel medical imaging technique: hyperpolarized 13C-MRI and newly developed metabolic inhibitors to evaluate metabolic characteristics ("glycolytic" and "OxPhos" status) in colorectal cancer tissues in vivo and to select treatment according to these characteristics. The method also enables the determination of drug efficacy and treatment prediction at a time.

Free Research Field

大腸がん

Academic Significance and Societal Importance of the Research Achievements

解糖系の亢進はがん代謝の特徴とされているが、大腸癌細胞内でピルビン酸代謝には解糖系とOxPhos系の相互の可塑性が存在し、この可塑性を標的とすることが重要であることを明らかにした。
新規開発された代謝阻害剤と超偏極13C-MRI用いて、治療効果予測を行う手法を確立した。この手法は大腸がん診断初期に治療効果判定（予測）を行える利点があること、及び、他の抗がん剤でも応用可能と考えられる。進行大腸がんや非切除因子をもつ大腸がん患者に対する治療戦略を診断早期に決定でき、適切な外科的手術介入の範囲・タイミングをより詳細に決定できるなどの効果をもたらし、大腸がん治療の成績向上への貢献が期待される。