TOPICAL APPLICATION OF A FIRST PORPHYCENE DYE FOR PHOTODYNAMIC THERAPY - PENETRATION STUDIES IN HUMAN PERILESIONAL SKIN AND BASAL-CELL CARCINOMA

Photodynamic therapy (PDT) in dermatology has been proven to be a succ essful noninvasive therapeutic modality for treating skin cancer To fa cilitate its clinical introduction, the development of topical photose nsitizers is necessary to avoid generalized, cutaneous photosensitivit y. Therefore the penetration of synthetic chemically pure -2,7,12,17-t etrakis-(beta-methoxyethyl)-porphycene (ATMPn) into human skin was stu died, Single specimens of freshly excised perilesional skin (n = 70) a nd basal cell carcinomas (n = 28) mere evaluated after topical applica tion of ethanolic ATMPn solutions (0.1% and 0.05%) for various times ( 2, 6, 16, 20 h). The penetration depth of ATMPn, recognized as red flu orescence in cryostat sections, was determined qualitatively by fluore scence imaging using a system of scoring related to the morphological structure of human skin (0 no fluorescence, 5 fluorescence deeper than basement membrane), Perilesional skin incubated for 2 or 6 h revealed fluorescence restricted to the upper parts of the epidermis, while af ter 16 or 20 h of incubation fluorescence was detected down to the bas ement membrane resulting in a significantly higher score (mean sum of scores : 2 h 2.6 +/- 0.4; 6 h 3.2 +/- 0.1; 16 h 3.8 +/- 0.1; 20 h 3.6 +/- 0.1). Quantitative evaluation by digital image analysis confirmed the qualitative results. Fluorescence was limited to the epidermis and the fluorescence intensity of the epidermis mas higher after 16 h (4. 9% of the fluorescence standard) than after 6 h (4.1%) incubation, Bas al cell carcinomas showed fluorescence in the deep dermis as early as after 6 h incubation, but restricted to tumour cell nests, These resul ts suggest that penetration of ATMPn into tumour tissue after topical application might be sufficient for topical PDT and that poor penetrat ion into surrounding tissue might prevent scar formation following irr adiation for PDT. The penetration characteristics of ATMPn now have to be proven in an in vivo setting.