Porphyrins Preferentially Accumulate in a Melanoma Following Intravenous Injection of 5-Aminolevulinic Acid

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Abstract
Systemically, as opposed to topically, administered 5-aminolevulinic acid (ALA) is of increasing interest for photodynamic therapy (PDT) because of more selective and more homogeneous accumulation of porphyrins in neoplastic tissues. This study investigates the profile and the time course of porphyrin metabolites in various tissues following intravenous injection of ALA (0.5 g/kg body weight) into hamsters bearing an amelanotic melanoma (A-Mel-3). ALA injection led to maximum levels of ALA and porphyrins in erythrocytes after 45 min. In tissues, maximum porphyrin levels were detected after 45 min (tumor), 4 h (skin, kidney), and 24 h (liver). Sixfold higher porphyrin levels were observed in tumors as compared to surrounding normal skin at 45 min. Predominant porphyrin metabolites were protoporphyrin (tumor, skin, liver, kidney), coproporphyrin (tumor) and highly carboxylated porphyrins (tumor, skin, kidney). These data suggest optimum efficacy of light irradiation in systemic PDT with ALA within the first two hours after injection. Tumor-specific ALA metabolism yields protoporphyrin and coproporphyrin as the prevailing porphyrin metabolites.

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