Development of therapeutic effect prediction method and cancer therapy enhancement method for internal radiation therapy (Fostering Joint International Research)

• Project/Area Number: 16KK0200
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: Kobayashi Masato 金沢大学, 保健学系, 准教授 (30444235)
• Project Period (FY): 2017 – 2019
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
• Keywords: 核医学 / イメージング / SPECT / 排泄型薬物トランスポータ / 内用放射線治療 / [131I]MIBG / トランスポータ / 多剤耐性 / がん / 個別化治療 / 放射性薬剤

Outline of Final Research Achievements

In this study, we aimed to improve the therapeutic effect of [131I] MIBG, an internal radiotherapy with radiopharmaceuticals for cancer, by using a method for predicting the therapeutic effect of [131I] MIBG and develop the cancer therapy enhancement method with combination of [131I] MIBG and the specific inhibitors for efflux transporter from cancer cells.In international collaborators in the United States, [131I] MIBG was excreted outside cancer cells via MRP1 and MRP4 in human-derived neuroblastoma cell line SK-N-SH, which is the target of treatment of [131I] MIBG. cancer cells. In addition, we have developed the cancer therapy enhancement method by using MRP-specific inhibitor MK-571 and probenecid to retain [131I] MIBG in cancer cells.

Academic Significance and Societal Importance of the Research Achievements

本国際共同研究では、小児がんの神経芽細胞腫に対する内用放射線治療薬[131I]MIBGの治療効果予測法と、[131I]MIBGのがん治療効果増強法の開発に成功した。本研究成果により、[131I]MIBG投与前に、[131I]MIBGを用いた神経芽細胞腫に対する治療効果を予測できる。また、[131I]MIBGのがん細胞排泄阻害剤を併用投与することで、[131I]MIBGのがん治療効果を増強できる可能性を示した。

Research Products

• [Int'l Joint Research] スタンフォード大学(米国) (2019)
  • Year and Date: 2019-03-24
• [Int'l Joint Research] テキサス大学MDアンダーソンがんセンター(米国) (2018)
• [Int'l Joint Research] 米国国立衛生研究所(米国) (2018)
• [Journal Article] Transport mechanism and affinity of [99mTc]mercaptoacetyltriglycine ([99mTc]MAG3) on the apical membrane of renal proximal tubule cells. (2020)
  • Author(s): Kobayashi M, Nishi K, Mizutani A, Okudaira H, Nakanishi T, Shikano N, Nishii R, Tamai I, Kawai K.
  • Journal Title: Nuclear Medicine and Biology. Volume: 84-85 Pages: 33-37
  • DOI: 10.1016/j.nucmedbio.2020.01.002
  • Peer Reviewed
• [Journal Article] Imaging of Hepatic Drug Transporters with [131I]6-β-iodomethyl-19-norcholesterol. (2019)
  • Author(s): Kobayashi M., Nishi K., Mizutani A., Hokama T., Matsue M., Tsujikawa T., Nakanishi T., Nishii R., Tamai I., Kawai K.
  • Journal Title: Sci. Rep. Volume: 9 Issue: 1 Pages: 13413-13413
  • DOI: 10.1038/s41598-019-50049-8
  • Peer Reviewed / Open Access
• [Patent(Industrial Property Rights)] 細菌感染症の放射性診断薬 (2019)
  • Inventor(s): 川井恵一，小林正和，水谷明日香，岡本成史
  • Industrial Property Rights Holder: 川井恵一，小林正和，水谷明日香，岡本成史
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
• [Patent(Industrial Property Rights)] 細菌又は細胞の分類方法，アミノ酸の輸送特性の分類方法，菌感染の診断補助方法並びに癌の診断補助方法 (2019)
  • Inventor(s): 川井恵一，小林正和，水谷明日香，岡本成史
  • Industrial Property Rights Holder: 川井恵一，小林正和，水谷明日香，岡本成史
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019