Examination of radiotherapy combined with TH-302 using FRP-170-PET for hypoxia imaging

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16717
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Osaka University (2021-2022); Hirosaki University (2020)
• Principal Investigator: Ichise Koji 大阪大学, 大学院医学系研究科, 招へい教員 (50832903)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: TH-302 / FRP170 / 腫瘍内低酸素 / 治療抵抗性分画 / 低酸素イメージング / 低酸素毒 / 放射線治療増感剤

Outline of Final Research Achievements

To improve the efficacy of radiotherapy, it is important to establish sensitization methods that target intratumoral hypoxic cells, and hypoxic imaging to discriminate targets for which these treatments are effective. In this study, we focused on TH-302, a hypoxic cytotoxin, and 18F-FRP170, a novel hypoxia tracer for positron emission tomography (PET). In human tongue cancer cell line SAS, TH-302 showed stronger hypoxia-selective toxicity than tirapazamine, a conventional hypoxic cytotoxin. 18F-FRP170 was administered to SAS tumor-implanted mice, and PET imaging was performed after 60 and 120 minutes. The results suggested that 18F-FRP170 was appropriate to evaluate PET accumulation at 120 minutes after administration. We compared the percentage of tumor areas with a high tumor:blood ratio in PET and the fraction of pimonidazole-positive areas in tumor tissue. As a result, it was suggested that accumulation of 18F-FRP170-PET might reflect the hypoxic region in the tumor.

Free Research Field

放射線腫瘍学

Academic Significance and Societal Importance of the Research Achievements

近年開発された低酸素トレーサー18F-FRP170は、従来のFMISOの脂溶性を低減させ組織移行性、クリアランスを改善させた薬剤であり、生体における低酸素組織をより短時間で可視化することができる。18F-FRP170-PETを低酸素イメージングに用いることで、検査に要する煩雑さを軽減することができれば、日常臨床における低酸素増感剤の臨床応用はより現実性を増すだろう。極めて有望な薬剤であるものの、18F-FRP170に関する基礎的な検討はまだ十分には行われていない。本課題で得られた結果は、今後18F-FRP170-PETを用いた低酸素イメージングの研究を進める上で重要な知見となりえる。