Selective accumulation of ALA-induced PpIX and photodynamic effect in chemically induced hepatocellular carcinoma

Abstract

The possibility of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) for liver cancer was investigated using a chemically induced hepatocellular carcinoma (HCC) model. Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT. We determined the fluorescence intensity of PpIX in HCC and nontumoral tissue in the liver. 5-Aminolaevulinic acid was intravenously injected to male Fisher rats with HCC at a dose of 500 mg kg À1 , and the fluorescence intensity in each tissue sample excised from liver was measured with a spectrofluorometer at 1, 3 and 6 h after administration. Fluorescence intensity was at a peak of 3 h after administration in both HCC and nontumoral tissue. The accumulation of PpIX in HCC was higher than that in the nontumoral tissue at 1 h (Po0.001) and 3 h (Po0.05) after ALA administration. Based on these results, PDT was performed on HCC at 3 h after 500 mg kg À1 ALA administration before laser irradiation of 30 J per tumour. Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC. These findings suggest the possibility to detect HCC by fluorescence and to treat HCC by light.

The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme

“…Cellular Protoporphyrin IX Measurements-Cellular protoporphyrin IX concentration was measured as described previously (23). Briefly, cells were harvested and washed once with PBS, and protoporphyrin IX concentration was measured by using a Vantage flow cytometer (BD Biosciences).…”

Selective accumulation of PpIX and photodynamic effect after aminolevulinic acid treatment of human adenomyosis xenografts in nude mice

“…Otake et al (18) compared PpIX fluorescence intensity in HCC and nontumoral tissues and determined that intensities were higher at 3 hours than at either 1 hour or 6 hours after ALA administration in a chemically induced hepatocellular carcinoma model. In our experiments, the maximum fluorescence intensity of PpIX in human adenomyosis tissue also was detected at 3 hours.…”

Physicochemical Properties of Protoporphyrin IX by Metal Ions in Acetonitrile-Water Mixture Solution

“…Recently, photodynamic therapy has been used in the management of various malignant tumors, including cancers of the skin, gastrointestinal tract, lung and uterus. 1 It is, however, necessary to use an appropriate photosensitizer and light source to enhance the efficiency of photodynamic therapy. One of the most important porphyrin derivatives is protoporphyrin IX, which has attracted considerable attention for use in photodynamic therapy of skin tumors.…”

“…[2][3][4] Protoporphyrin IX is produced in the haem biosynthesis pathway of biological systems. 1,5 It is normally formed in vivo from the reactants glycine and succinyl-coenzyme A in the mitochondria and then converted into the actual photosensitizer, protoporphyrin IX. 6 When protoporphyrin IX is electronically excited by the absorption of light, the substance emits fluorescence strongly and photobleaches rapidly under formation of singlet oxygen.…”