Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer

δ-Aminolevulinic Acid Transport in Cancer Cells of the Human Extrahepatic Biliary Duct

“…Bile duct stenosis could be almost completely eliminated in the treated area by PDT with photosan-3 (Rumalla et al, 2001;Zoepf et al, 2001a). In a pilot study, PDT with ␦-ALA was not effective (Zoepf et al, 2001b). Possible explanations are specific biochemical characteristics in bile duct cancer that are different from other epithelial tumors, thereby requiring optimization of treatment parameters.…”

“…Under physiological conditions, ␦-ALA is required for the synthesis of protoporphyrin IX, a direct precursor of heme. Endogenously generated protoporphyrin IX is an excellent, socalled second-generation photosensitizing agent (Zoepf et al, 2001b). After oral or intravenous application of ␦-ALA, the ␦-ALA synthase is bypassed and porphyrins such as protoporphyrin IX accumulate in cells above normal level.…”

5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol)-chitosan copolymer for photodynamic therapy

“…12 Otherwise, the high aqueous solubility of 5-ALA and its low bioavailability have frequently been discussed as drawbacks to its clinical application. 1,2,6,10 To overcome these problems, chemical modification of 5-ALA, 5-ALA-incorporated nanocolloid, patch-based delivery system, or liposomal carriers were tried, in order to improve delivery of 5-ALA. 14,15,18,19 Chitosan has been extensively investigated as a geneor drug-delivery carrier. [25][26][27][28][33][34][35] In particular, chitosan is known to enhance mucosal transport or delivery of bioactive agents.…”

“…1 Basically, 5-ALA alone is not a photosensitizer; ie, it gets interconverted to a strong photosensitizer, protoporphyrin IX (PpIX), via the heme biosynthetic pathway in the mitochondria, which then functions as a photosensitizer. 1,10 Successful cases of suppression of solid tumors by excessive administration of 5-ALA have been reported. 1,[10][11][12] In addition to these successful experiences, some drawbacks of 5-ALA, such as hydrophilicity and low specificity for tumor cells, have been noted to induce lower cellular uptake and low bioavailability of ALA. 13 To overcome these drawbacks, various kinds of modified 5-ALA have been developed.…”

“…1,10 Successful cases of suppression of solid tumors by excessive administration of 5-ALA have been reported. 1,[10][11][12] In addition to these successful experiences, some drawbacks of 5-ALA, such as hydrophilicity and low specificity for tumor cells, have been noted to induce lower cellular uptake and low bioavailability of ALA. 13 To overcome these drawbacks, various kinds of modified 5-ALA have been developed. [14][15][16] For example, esterification of ALA, such as methyl-or hexyl-ester conjugated 5-ALA was reported to show enhanced cellular uptake and a better interconversion rate to PpIX than the parent compound.…”