Development of a photodynamic therapy using Indocyanine green dye and near-infrared laser for hepatocellular carcinoma

• Project/Area Number: 26462039
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Kaneko Junichi 東京大学, 医学部附属病院, 講師 (50328118)
• Co-Investigator(Renkei-kenkyūsha): INAGAKI Yoshinori 東京大学, 医学部附属病院, 助教 (40733390)
• Research Collaborator: URANO Yasuteru ; KOKUDO Takashi ; SHIRATA Chikara ; KIRITANI Sho ; SATO Masamitsu
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肝細胞癌 / indocyanine green / 光線力学的治療 / 光線力学療法 / Indocyanine green / 近赤外光 / レーザー

Outline of Final Research Achievements

We developed, a new anti-cancer treatment, the photodynamic therapy (PDT) using Indocyanine green (ICG) and near-infrared (NIR) laser for hepatocellular carcinoma (HCC). However, a molecular mechanism underlying this effect needs to be elucidated. HuH-7 cells, a well-differentiated human HCC cell line, were transplanted subcutaneously into BALB/c-nu/nu mice. ICG was administered 24h before NIR irradiation. The irradiation was performed by 823-nm NIR laser. The temperature of HuH-7 xenografts rose to 49C. The cell toxicity of ICG-NIR was inhibited by cooling sheet. Reactive oxygen species (ROS) production was detected in vitro and in vivo, and the ROS production was inhibited under with a cooling sheet. Repeat NIR irradiation increased the cell toxicity. The mean tumor volume growth on day 9 was significantly suppressed (p<0.01). Apoptosis of HCC cells after ICG-NIR PDT is caused by heat production mediated ROS production. Repeated ICG-NIR irradiation improves the anti-tumor effect.

Research Products

• [Journal Article] Diagnostic accuracy of indocyanine green fluorescence imaging and multidetector row computed tomography for identifying hepatocellular carcinoma with liver explant correlation (2017)
  • Author(s): Masuda, K. Kaneko, J. Kawaguchi, Y. Togashi, J. Arita, J. Akamatsu, N. Sakamoto, Y. Hasegawa, K. Sumihito, T. Kokudo, N.
  • Journal Title: Hepatol Res. Volume: Epub ahead of print Issue: 12 Pages: 1-9
  • DOI: 10.1111/hepr.12870
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Photodynamic therapy with indocyanine green induces apoptosis of hepatocellular carcinoma cells through heat-mediated oxidative stress (2017)
  • Author(s): Chikara Shirata, Junichi Kaneko, Yoshinori Inagaki, Takashi Kokudo, Masumitsu Sato, Sho Kiritani, Nobuhisa Akamatsu, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo.
  • Journal Title: Scientific reports Volume: 未定
  • Peer Reviewed
• [Journal Article] Interleukin-2 receptor antagonist immunosuppression and consecutive viral management in living-donor liver transplantation for human immunodeficiency virus/hepatitis C-co-infected patients: a report of 2 cases (2016)
  • Author(s): Harufumi Maki, Junichi Kaneko, Satoshi Yamamoto, Nobuhisa Akamatsu, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Tomohiro Tanaka, Sumihito Tamura, Yasuhiko Sugawara, Kunihisa Tsukada, Norihiro Kokudo
  • Journal Title: Clin J Gastroenterol. Volume: 9 Issue: 1 Pages: 32-37
  • DOI: 10.1007/s12328-015-0621-8
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Photodynamic therapy for human hepatoma-cell line tumors utilizing biliary-excretion properties of indocyanine green (2017)
  • Author(s): Junichi Kaneko, Yoshinori Inagaki, Takashi Kokudo, Chikara Shirata, Sho Kiritani, Masumitsu Sato, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo
  • Organizer: 16th International Photodynamic Association World Congress
  • Place of Presentation: Coimbra, Portugal
  • Year and Date: 2017-06-08
  • Int'l Joint Research
• [Presentation] Indocyanine green蛍光肝細胞がんに対する近赤外レーザー光照射による光線力学療法 (2016)
  • Author(s): 金子順一、長谷川潔、國土典宏
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2016-05-19
• [Presentation] Indocyanine green蛍光肝細胞癌に対する近赤外光照射による光線力学療法 (2016)
  • Author(s): 白田力，金子順一，稲垣善則，國土貴嗣，有田淳一，赤松延久，阪本良弘，長谷川潔，國土典宏
  • Organizer: 東京大学医学部附属病院先端医療シーズ開発フォーラム2016「アカデミアからの挑戦」
  • Place of Presentation: 東京大学伊藤国際学術研究センター
  • Year and Date: 2016-02-02
• [Presentation] Indocyanine green蛍光肝細胞癌に対する近赤外光照射による光線力学療法 (2016)
  • Author(s): 白田力，金子順一，稲垣善則，國土貴嗣，有田淳一，赤松延久，阪本良弘，長谷川潔，國土典宏
  • Organizer: 第26回日本光線力学学会
  • Place of Presentation: 横浜
• [Presentation] Near Infrared Photodynamic Therapy Using Indocyanine Green Inhibits Tumor Growth Of Human Hepatocellular Carcinoma (2015)
  • Author(s): Chikara Shirata, Junichi kaneko, Yoshihiro Inagaki, Takashi Kokudo, Satoshi Yamamoto, Nobuhisa Akamatsu, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo
  • Organizer: International Liver Cancer Association 9th Annual Conference
  • Place of Presentation: Paris, France
  • Year and Date: 2015-09-04 – 2015-09-06
• [Presentation] Near Infrared Photodynamic Therapy Using Indocyanine Green Inhibits Tumor Growth Of Human Hepatocellular Carcinoma (2015)
  • Author(s): Chikara Shirata, Junichi kaneko, Yoshihiro Inagaki, Takashi Kokudo, Satoshi Yamamoto, Nobuhisa Akamatsu, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo
  • Organizer: International Liver Cancer Association
  • Place of Presentation: Paris
  • Year and Date: 2015-09-04
  • Int'l Joint Research
• [Presentation] Inhibition of human hepatoma-cell-line tumor growth by near infrared photodynamic therapy with indocyanine green. (2015)
  • Author(s): Yoshihiro Inagaki, Junichi Kaneko, Chikara Shirata, Takashi Kokudo, Satoshi Yamamoto, Nobuhisa Akamatsu, Junichi Arita, Wei Tang, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo
  • Organizer: 第15回東京大学生命科学シンポジウム
  • Place of Presentation: 武田先端知ビル 武田ホール
  • Year and Date: 2015-06-27
• [Presentation] Indocyamine green蛍光肝細胞癌に対する腹腔鏡下ないし開腹下近赤外光レーザー照射による光線力学療法 (2015)
  • Author(s): 金子順一、稲垣善則、白田力、國土貴嗣、山本訓史、赤松延久、有田淳一、阪本良弘、唐子尭、長谷川潔、國土典宏
  • Organizer: 第69 回手術手技研究会
  • Place of Presentation: 群馬県、高崎市
  • Year and Date: 2015-05-16
• [Presentation] Indocyanine green蛍光肝細胞癌に対する腹腔鏡下ないし開腹下近赤外光レーザー照射による光線力学療法 (2015)
  • Author(s): 金子順一、稲垣善則、白田力、國土貴嗣、山本訓史、赤松延久、有田淳一、阪本良弘、唐子尭、長谷川潔、國土典宏
  • Organizer: 第69回手術手技研究会
  • Place of Presentation: 高崎
  • Year and Date: 2015-05-15
• [Book] Fluorescence Imaging for Surgeons (2016)
  • Author(s): Junichi Kaneko, Yoshinori Inagaki, Takeaki Ishizawa, Norihiro Kokudo
  • Total Pages: 351
  • Publisher: Springer International Publishing
• [Book] Concepts and Applications of Fluorescence Imaging for Surgeons (2015)
  • Author(s): Junichi Kaneko, Yoshinori Inagaki, Takeaki Ishizawa, Norihiro Kokudo
  • Total Pages: 9
  • Publisher: Springer