Photodynamic Diagnosis of Hepatocellular Carcinoma Using 5-Aminolevulinic Acid

Anticancer Res. 2016 Sep;36(9):4569-74. doi: 10.21873/anticanres.11005.

Abstract

Backgtound/Aim: Since hepatocellular carcinoma (HCC) has a high recurrence rate, accurate diagnosis of its location and curative resection is important to improve survival. This study evaluated the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) for HCC.

Materials and methods: We used two human hepatoma cell lines (HuH-7 and Hep G2). Cells were treated with 5-ALA for 4 h. 5-ALA-induced fluorescence was then examined under a fluorescence microscope. We designed hepatoma mouse models, with mice receiving an intraperitoneal injection of 5-ALA. After 4 h, their liver tumors were removed and examined under a fluorescence microscope. We also analyzed 12 HCC patients who underwent curative liver resection. The patients were administered 5-ALA orally before surgery. The excised livers were sectioned and examined by fluorescence microscopy.

Results: In vitro and in vivo, red fluorescence of protoporphyrin IX (PpIX) was observed in tumors. In 11 of 12 patients, red fluorescence was observed in their HCC. The tumor of only one patient did not exhibit red fluorescence because it had been necrosed by transcatheter arterial chemoembolization (TACE).

Conclusion: Red fluorescence of PpIX was observed in hepatoma cells, tumors of HCC mouse models and HCC of patients. PDD of HCC using 5-ALA is simple and may be useful for real-time diagnosis during liver resection.

Keywords: 5-aminolevulinic acid; Hepatocellular carcinoma; photodynamic diagnosis; protoporphyrin IX.

MeSH terms

  • Aged
  • Aminolevulinic Acid / chemistry*
  • Animals
  • Carcinoma, Hepatocellular / drug therapy*
  • Cell Line, Tumor
  • Embolization, Therapeutic
  • Female
  • Hep G2 Cells
  • Humans
  • Liver / surgery
  • Liver Neoplasms / drug therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Fluorescence
  • Middle Aged
  • Photochemotherapy / methods
  • Photosensitizing Agents / chemistry*
  • Protoporphyrins / chemistry

Substances

  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX