Visualization of whole body dynamics of PD-1 in vivo using radiographic tomography

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15763
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Okonogi Noriyuki 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 重粒子線治療研究部, 医長(定常) (00750572)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: PD-1 / 放射断層撮影

Outline of Final Research Achievements

We performed a basic study to evaluate whole body dynamics of Program death-1 (PD-1) in vivo by image examination. In order to enable examination by emission tomography represented by PET examination, we first developed a labeled drug. The labeled drug, 64Cu (half-life 13 hours) labeled anti-PD-1 antibody, bound to PD-1, and the binding stability up to 48 hours was confirmed. Next, the developed drug was administered to normal mice, and PET imaging was performed. We found that the 64Cu-labeled anti-PD-1 antibody was widely distributed in the liver and further distributed in the spleen and intestinal lymph nodes. Furthermore, these experiments were performed also in tumor-grafted mice, and confirmed that the 64Cu-labeled anti-PD-1 antibody was also distributed in the tumor.

Free Research Field

放射線医学

Academic Significance and Societal Importance of the Research Achievements

近年、抗PD-1抗体に代表される、免疫チェックポイント阻害薬の有効性が数多く報告されている。しかしながら、免疫チェックポイント阻害薬は全ての患者に有効という訳ではなく、治療効果予測が現状の喫緊の課題の一つである。また、薬剤の至適投与期間については、学術的、医療経済学的にも重要な課題である。非侵襲的に、繰り返し施行可能な評価方法の確立は、これらの薬剤の適正な使用に貢献するものと考える。本研究はマウスを用いた、基礎的研究であるが、この結果を元に臨床応用を目指す。