Tissue distribution and penetration of 5-ALA induced fluorescence in an amelanotic melanoma after topical application.

摘要

BACKGROUND: Photodynamic therapy (PDT) following topical application of 5-aminolevulinic acid (ALA) is increasingly employed for several types of malignancies. However, data with respect to tissue penetration and distribution of ALA-induced porphyrins after topical application are scarce. Therefore, it was our aim to study tissue distribution and the penetration potency of topically applied ALA. MATERIAL AND METHODS: We used Syrian golden hamsters implanted with the amelanotic melanoma A-Mel-3 growing in a transparent dorsal skinfold chamber. ALA was topically applied in aqueous solution at a concentration of 3% for 4 hours. The fluorescence pattern was quantified by fluorescence microscopy and digital image analysis from cryosections and given as percentage of a reference standard in medians (25%, 75% quartiles). RESULTS: Fluorescence intensities in tumors were 90.8% (56.2%, 115.2% of a reference standard, p < 0.01 vs. normal tissue) significantly exceeding normal surrounding host tissue yielding fluorescence intensities of 12.1% (9.1%, 16.1%). The tumor selectivity, that is the ratio of fluorescence intensities between tumor and normal tissue, was 7.3 (6.1, 9.1). For superficial tumors with a thickness of approximately 1 mm no fluorescence gradients after topical application of ALA could be observed. CONCLUSION: In superficial cancerous lesions the fluorescence distribution of ALA induced porphyrins is tumor selective without significant fluorescence gradients throughout the tumor. Thus, by optimising the treatment modalities for topical ALA-PDT an enhanced efficacy and selectivity will be reached.