LACK OF SELECTIVITY OF PROTOPORPHYRIN-IX FLUORESCENCE FOR BASAL-CELL CARCINOMA AFTER TOPICAL APPLICATION OF 5-AMINOLEVULINIC ACID - IMPLICATIONS FOR PHOTODYNAMIC TREATMENT

Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates, Exogenous 5-am ino-levulinic acid (ALA) is converted by intracellular enzymes to phot oactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cyto toxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX productio n by tumors in such trials, and to assess the usefulness of PpIX for m arking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied unde r occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in viv o photography, ex vivo video fluorescence imaging, and fluorescence mi croscopy. External macroscopic PpIX fluorescence, as assessed by in vi vo and ex vivo imaging, correlated with the clinical presence of BCC, Examination by a digital imaging fluorescence microscope revealed inte r- and intratumor fluorescence variability and heterogeneity, PpIX flu orescence corresponding to full tomor thickness was found in six super ficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observe d in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appea red to provide little or no PpIX in deep tumor lobules. In addition, n o selectivity for tumor tissue versus normal epidermis was seen. The g rossly brighter external PpIX fluorescence over tumors may be due, the refore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness. The absence of reproducible fluorescence marking of nodular and infiltrating BCC suggests that topical ALA, at least under the present delivery protocols, may not be a reliable regi men for photodynamic treatment of these BCCs.