Analysis and imaging of abnormal metabolism in tumor using PET probes

• Project/Area Number: 15K19834
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Okada Maki 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 標識薬剤開発部, 研究員(任常) (00415407)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 酢酸 / IDH / ピルビン酸 / α-ケトグルタル酸 / 2-ヒドロキシグルタル酸 / 11C酢酸 / グルタミノリシス

Outline of Final Research Achievements

In vitro tumor cell study, intracellular radioactivity derived from[1-11C]acetate mainly presented as aqueous metabolites like organic acid and amino acids in the earlier phase and then decreased accompanied with increasing ratio of lipophilic metabolites like phospholipid. [1-11C]acetate uptake and lipophilic metabolites production in tumor cell were seemed to be depended on glutamine presence. [Carbonyl-11C]N-methyl-4- piperidyl acetate (MP4A) was successfully radiosynthesized and was well taken up into rat brain followed by represented similar kinetics with the other [1-11C]acetate pro-probe, which indicates [carbonyl-11C]MP4A was seemed to have a potential as cell permeable pro-probe of [1-11C]acetate.

Academic Significance and Societal Importance of the Research Achievements

本研究ではがん細胞内の代謝リプログラミングの測定と新規測定法の確立を目的とした。がん細胞内における酢酸の代謝を測定し、グルタミンがエネルギー代謝のみならず腫瘍細胞内での脂質合成に関与していることが示唆された。また今後、[1-11C]α-ケトグルタル酸等のPETプローブの開発がさらに進むことによってイソクエン酸脱水素酵素(IDH)の突然変異によって生じる2-ヒドロキシグルタル酸（2-D-HG）の生成・蓄積をイメージング化することが可能となり、IDH変異の有無による予後や治療計画に大きな影響を与えることは言うまでもない。