Redox imaging of Breast Cancer Animal Model by DNP-MRI

• Project/Area Number: 19K08225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Gifu University
• Principal Investigator: Nozawa Asae 岐阜大学, 大学院医学系研究科, 特任助教 (90802786)
• 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) ; 松尾 政之 岐阜大学, 大学院医学系研究科, 教授 (40377669) ; 田中 秀和 山口大学, 大学院医学系研究科, 教授 (30509782)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: レドックス / 乳癌 / DNP / レドックス代謝 / イメージング / MRI / 超偏極

Outline of Research at the Start

乳がんの死亡率は年々増加傾向にあり、遺伝子技術の進化にともない薬剤耐性を示すホルモン受容体とHER2受容体をもたないトリプルネガティブ乳がん（TNBC）の存在が明らかとなり新たな診断と治療法の開発が急務である。本研究は超偏極MRI（DNP-MRI）法で乳がんのレドックス代謝を非侵襲的に解析し、レドックス代謝に基づく乳がん診断法を確立することを目的とする。

Outline of Final Research Achievements

It is known that abnormal redox status of tumors is a cause of resistance in anticancer drugs and radiotherapy. In this study, we conducted basic research on redox imaging of tumors by redox probe/ in vivo DNP-MRI using a mouse model of breast cancer tumors. In some breast cancer cells, poor probe distribution were observed due to intratumoral necrosis and low vascularity. On the other hand, in a mouse model of spontaneous breast cancer, the DNP probe was rapidly distributed throughout the tumor and provided clear redox images. This technique is expected to be applied to early diagnosis of tumors in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究により、乳がんにおける創薬では、薬効評価までの時間短縮に伴う創薬過程の加速化とランニングコストの軽減、実臨床においては、早期の治療効果の予測による患者のQOLの向上が見込まれる

Research Products

• [Journal Article] Spatiotemporal imaging of redox status using in vivo dynamic nuclear polarization magnetic resonance imaging system for early monitoring of response to radiation treatment of tumor (2022)
  • Author(s): Koyasu Norikazu、Hyodo Fuminori、Iwasaki Ryota、Eto Hinako、Elhelaly Abdelazim Elsayed、Tomita Hiroyuki、Shoda Shinichi、Takasu Masaki、Mori Takashi、Murata Masaharu、Hara Akira、Noda Yoshifumi、Kato Hiroki、Matsuo Masayuki
  • Journal Title: Free Radical Biology and Medicine Volume: 179 Pages: 170-180
  • DOI: 10.1016/j.freeradbiomed.2021.12.311
  • Peer Reviewed
• [Journal Article] <i>In Vivo</i> Dynamic Nuclear Polarization Magnetic Resonance Imaging for the Evaluation of Redox-Related Diseases and Theranostics (2022)
  • Author(s): Hyodo Fuminori、Eto Hinako、Naganuma Tatsuya、Koyasu Norikazu、Elhelaly Abdelazim Elsayed、Noda Yoshifumi、Kato Hiroki、Murata Masaharu、Akahoshi Tomohiko、Hashizume Makoto、Utsumi Hideo、Matsuo Masayuki
  • Journal Title: Antioxidants &amp; Redox Signaling Volume: 36 Issue: 1-3 Pages: 172-184
  • DOI: 10.1089/ars.2021.0087
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Dynamic Nuclear Polarization(DNP) MRI for imaging tissue metabolism Application of dissolution DNP and in vivo DNP to animal disease models (2021)
  • Author(s): Fuminori Hyodo, Masaharu Murata, Hinako Eto, Norikazu Koyasu, Ryota Iwasaki, Abdelazim Elhelaly, Takashi Mori, Yoshifumi Noda, Hiroki Kato, and Masayuki Matsuo
  • Organizer: ISMAR・APNMR・NMRSJ・SEST2021
  • Int'l Joint Research / Invited
• [Presentation] Application of Hyperpolarized 13C pyruvate MRS for early evaluation of anti-cancer treatmen (2021)
  • Author(s): Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Norikazu Koyasu, Hiroyuki Tomita, Masaharu Murata, Yoshifumi Noda, Hiroki Kato, Masayuki Matsuo
  • Organizer: AMSRM and ASMRM