Photosensitization of experimental hepatocellular carcinoma with protoporphyrin synthesized from administered δ-aminolevulinic acid: Studies with cultured cells and implanted tumors

Background/Aims: Photodynamic therapy using porphyrins or related compounds and laser light is an investigational treatment for neoplasms. The aim of this study was to establish whether this might be applicable for hepatocellular carcinoma using protoporphyrin synthesized in the tissue from administered δ-aminolevulinic acid. Methods: We measured porphyrin accumulation in normal rat hepatocytes and Morris hepatoma cells in culture, and in subcutaneously implanted hepatomas and other tissues of the rat after administration of δ-aminolevulinic acid, and assessed cell and tissue damage after application of laser light. Results: Porphyrin accumulation after δ-aminolevulinic acid was added to the medium was greater and continued to increase for a longer period of time in hepatoma cells than in hepatocytes (1337 ± 42 vs 513 ± 31 fluorescence units/cell at 8 h, means ± SE, p < 0.001). After intraperitoneal injection of δ-aminolevulinic acid to rats with subcutaneously growing hepatomas, porphyrin content in tumor and liver was similar at 4 h but was higher in tumor at 6 h. Laser light caused necrosis of normal and malignant liver cells in culture and subcutaneous hepatomas in vivo. Conclusions: We conclude from these in vitro and in vivo studies that porphyrin accumulation after administration of δ-aminolevulinic acid in this hepatoma is substantial and time dependent, and delivery of laser light locally can cause tumor photosensitization and necrosis.