Topical and intratumoral photodynamic therapy with 5-aminolevulinic acid in a subcutaneous murine mammary adenocarcinoma

One of the most promising substances used in photodynamic therapy (PDT) is 5-aminolevulinic acid (ALA), which induces endogenous synthesis and accumul ation of porphyrins in malignant cells. In this paper we have shown that bo th topical and intratumoral administration of ALA in a subcutaneously impla nted mammary carcinoma produced a significant synthesis of porphyrins and s ubsequent sensitization to laser light. Porphyrin accumulation was greater when ALA was administered intratumorally and tumour/normal skin porphyrin c oncentration ratios were higher compared with topical application. Irradiat ion was optimal between 2 and 3 h after topical application of 50 mg of a 2 0% ALA cream and 2-4 h after intratumoral administration of 30 mg ALA/cm(3) . The pattern of tumour response evaluated as the delay of tumour growth wa s similar following either route of drug administration, Applications of PD T were performed once, twice or three times in the study. The response to s uccessive applications was constant for the same tumour, indicating that no resistance was acquired. Microscopic analysis showed both induction of foc i of necrosis and haemorrhage, morphological features of apoptotic cells an d total absence of cellular immune response. This paper reports on PDT with topical ALA in a subcutaneous carcinoma leading to tumour growth delay. Th ese findings may have great relevance in the treatment of cutaneous metasta sis of mammary carcinomas. (C) 1999 Elsevier Science Ireland Ltd. All right s reserved.