title: Photodynamic therapy for human hepatoma-cell-line tumors utilizing biliary excretion properties of indocyanine green.
abstract: BACKGROUND
  Photodynamic therapy (PDT) has not been reported for human hepatoma, because cancer cells only weakly take up the photosensitizer. Indocyanine green (ICG) is a photosensitizer normally excreted into the bile, and bile excretion is impaired in human hepatomas. We examined whether human hepatoma cell lines preferentially take up the ICG and then assessed the effectiveness of PDT using ICG and near-infrared (NIR) laser.
  
  
  METHODS
  HuH-7 and HepG2 human hepatoma cell lines were transplanted subcutaneously into mice. Developing HuH-7 and HepG2 tumors were confirmed that preferentially took up the ICG in 24 h after ICG was administered to mice via tail vein. The HuH-7 tumor showed a high tumor-to-background fluorescence intensity ratio, 255:1, whereas fluorescence intensity of HuH-7 is increased twofold compared to HepG2. HuH-7 cell transplanted mice were divided into three groups: ICG administration only (ICG+NIR-, n = 8), ICG and NIR laser exposure (ICG+NIR+, n = 12), and NIR laser exposure only (ICG-NIR+, n = 5).
  
  
  RESULTS
  Mean tumor volume in the ICG+NIR- and ICG-NIR+ groups increased steadily. In contrast, mean tumor volume in the ICG+NIR+ group did not change between days 0 and 3. Mean tumor volume did not differ significantly between the ICG-NIR+ and ICG-NIR- groups, but was significantly different between the ICG+NIR+ group and both the ICG-NIR+ and ICG+NIR- groups (p < 0.01).
  
  
  CONCLUSIONS
  ICG is preferentially taken up by HuH-7 and HepG2 human hepatoma cell line tumors. The tumor-to-background ratio of HuH-7 tumors, in particular, was extremely high. PDT with NIR laser irradiation suppressed HuH-7 human hepatoma cell line tumor growth.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kaneko
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Takeaki
authors.initials: T
authors.lastname: Ishizawa
authors.forename: Jianjun
authors.initials: J
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Taku
authors.initials: T
authors.lastname: Aoki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017319:Photosensitizing Agents; D007208:Indocyanine Green