Optimization of Cellular Function Modifying Techniques for Therapy of Solid Tumor by using Radiolabeled Liposomes

• Project/Area Number: 16K19877
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Hamamichi Shusei 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (60721686)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 放射性核種封入リポソーム / 放射性核種 / リポソーム / 固形がん / 内用療法

Outline of Final Research Achievements

Aim of this study was to compare accumulation levels of radiolabeled liposomes (i.e., In-111 EC, In-111 DTPA, etc.) in the tumor and other major tissues, and determine a technique that allowed increased tumor accumulation. Through analyzing radiolabeled liposomes by using multiple human cancer xenograft mice, we determined their biodistribution patterns, as well as necessity of these liposomes to be properly degraded in the RES for subsequent release of RI-ligand complexes. We also examined which transporter might be involved in the clearance of In-111 EC from the RES by treating RAW264 cells with various transporter inhibitors after phagocytosis of In-111 EC DSPG liposome. In addition, we determined that anti-cancer agent eribulin possessed a capacity to increase microvessel density in the tumor, as well as enhance tumor accumulation of radiolabeled liposome and anti-tumor effect of Doxil (liposomal anti-cancer agent).

Research Products

• [Journal Article] Antitumor effects of eribulin depend on modulatuin of the tumor microenvironment by vascular remodeling in mouse models. (2017)
  • Author(s): Ito K, Hamamichi S, Abe T, Akagi T, Shirota H, Kawano S, Asano M, Asano O, Yokoi A, MAtsui J, Umeda IO, Fujii H.
  • Journal Title: Cancer Science Volume: vol.108(11) Issue: 11 Pages: 2273-2280
  • DOI: 10.1111/cas.13392
  • Peer Reviewed / Open Access
• [Presentation] 放射性核種封入リポソームを用いたリポソーム化抗癌剤の薬効予測技術の開発 (2017)
  • Author(s): 濱道修生、梅田泉、藤井博史、伊藤憲、浅野誠、堀優作、岩田正夫、松井順二、船橋泰博
  • Organizer: 第86回日本核医学会関東甲信越地方会
  • Place of Presentation: 富士フィルム（株）西麻布本社講堂（東京都港区）
  • Year and Date: 2017-01-28
• [Presentation] Radiolabeled liposome and its application toward understanding cancer biology (2017)
  • Author(s): Hamamichi S
  • Organizer: The University of Alabama, Tuscaloosa, AL, USA
  • Invited
• [Presentation] Application of radiolabeled liposome to determine an indication for liposomal anti-cancer agent (2016)
  • Author(s): Hamamichi S
  • Organizer: The University of Alabama
  • Place of Presentation: Tuscaloosa, Alabama, USA
  • Year and Date: 2016-09-12
  • Invited
• [Presentation] SPECT/CT Imaging of 111In-ethylenedicysteine liposome demonstrates high tumor accumulation and rapid background clearance in a human cancer xenograft model (2016)
  • Author(s): Hamamichi S, Matsuura Y, Ohnuki K, Umeda IO, Fujii H
  • Organizer: World Molecular Imaging Congress 2016
  • Place of Presentation: New York City, USA
  • Year and Date: 2016-09-07
  • Int'l Joint Research