Porphyrin formation in actinic keratosis and basal cell carcinoma after topical application of methyl 5-aminolevulinate

Abstract

Photodynamic therapy using topical methyl 5-aminolevulinate (MAL) is a new treatment modality for basal cell carcinoma (BCC) and actinic keratosis (AK). MAL induces endogenous porphyrins, which act as photosensitizers. Pharmacokinetic studies of the porphyrin-inducing effect of MAL creams (Metvix) applied in different concentrations (16-160 mg/g) and application times are presented. Surface fluorescence measurements were used to monitor porphyrin accumulation in 18 superficial BCCs and 32 AKs. For both lesion types, the fluorescence increased during the first 13 of 28 hours of continuous MAL application. A 20-fold site-to-site variation was observed, and there were no significant MAL concentration dependencies. The selectivity between lesions and normal skin was 10-fold during the first hours and decreased throughout the application time. Fluorescence microscopy images of tissue sections from 32 nodular BCCs were analyzed to calculate the porphyrin content in tumor tissue as a function of depth. Significant correlation to MAL concentration was seen within the tumors treated for 3 hours. Increase to 18-hour MAL application enhanced the fluorescence levels in superficial tumor layers, but not in deep layers. In conclusion, application of the 160 mg/g cream for 3 hours gave advantageous porphyrin distributions for all types of lesions.