Noninvasive imaging of acquired gene mutations using singlet state hydrogen gas.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H06255
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Hokkaido University
• Principal Investigator: Matsumoto Shingo 北海道大学, 情報科学研究院, 准教授 (90741041)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 超偏極13C MRI / 遺伝子変異 / 代謝 / パラ水素誘起偏極

Outline of Final Research Achievements

Many of the pathogenic gene mutations are associated with characteristic metabolic changes. In this study, we developed a magnetic resonance imaging (MRI) technique that detects specific metabolic changes dependent on gene mutations by exciting the NMR signals of 13C-labeled biomolecules tens of thousands of times. We have succeeded in developing the hyperpolarization technique to enhance 13C NMR signals of biomolecules 50,000 to 100,000 times by using the hydrogenation of singlet state hydrogen gas, which can align quantum states relatively easily. Hyperpolarized 13C-pyruviate was administered to a tumor-bearing mouse, and production of lactate was confirmed according to the gene expression level of lactate dehydrogenase (LDH). MRI signal of 13C fumarate, which is used to detect gene mutations in the tumor suppressor genes fumarase and succinate dehydrogenase, could be enhanced more than 100,000 times, and succeeded to conduct metabolic MRI scan in mice.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

多くの急性・慢性疾患に遺伝的要因が関与する。先天的に受け継いだ遺伝子多型や変異であれば血液検査等により容易に検出できるが、突然変異等により後天的に獲得した遺伝子変異は、体内の奥深く、特定の臓器や組織のみに偏在し、その特定には侵襲的な生検採取が必要となる。もし変異により起こる特徴的な代謝変化をMRIで検出できれば、非侵襲的に後天的遺伝子変異の種類、位置、量を知ることが可能となる。超偏極13C MRIは13C標識した任意の化合物の生体内代謝を動的に計測する最先端技術である。本研究成果は、非侵襲的遺伝子診断としての価値に加え、数億円に上る現行の超偏極13C MRI導入コストの低減にも繋がる。