Development of podoplanin-targeted alpha-radioimmunotherapy and highly accurate dose evaluation method for complete recovery of malignant mesothelioma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07688
• 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: National Institutes for Quantum Science and Technology
• Principal Investigator: Sudo Hitomi 国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 分子イメージング診断治療研究部, 主任研究員 (10415416)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 放射免疫療法 / ポドプラニン / 中皮腫 / アクチニウム225

Outline of Final Research Achievements

Using a subcutaneous tumor model, we have demonstrated that radioimmunotherapy (RIT) with RI-labeled antibodies that specifically recognize podoplanin, which is highly expressed in mesothelioma, is a promising treatment for mesothelioma. In this study, we estimated the absorbed doses in tumors and organs and evaluated the therapeutic effect and side effects of 225Ac-labeled antibodies using an orthotopic mesothelioma model. Administration of 225Ac-labeled antibody via tail vein showed high therapeutic effect, but the absorbed doses in lungs and bone marrow were estimated higher than those of subcutaneous tumor model. Administration of labeled antibody into thoracic cavity suppressed the absorbed doses in lung and bone marrow and showed high therapeutic effect similarly iv injection. These results suggest that pleural administration of 225Ac-labeled anti-podoplanin antibodies is a promising treatment.

Free Research Field

核医学

Academic Significance and Societal Importance of the Research Achievements

α線放出核種である225Ac標識した抗ポドプラニン抗体が90Y標識した抗ポドプラニン抗体に比べ、より高い治療効果を持つことが示され、α線放出核種を用いたRIT(α-RIT)が中皮腫に対する有望な治療法になることが示唆された。
また、ポドプラニンは脳腫瘍など様々ながんで高発現していることが報告されており、本抗体を用いたα-RITが中皮腫以外の固形がんの治療法の開発に大きな進展をもたらすことが期待される。