Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles

The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumo urs. The aim of this work was to determine the kinetics of porphyrin genera tion in tissues after topical application of ALA delivered in different veh icles on the skin overlying the tumour and normal skin of mice. Maximal acc umulation was found in tumour 3 h after ALA application in both cream and l otion preparations. Normal and overlying tumour skin tissues showed differe nt kinetic patterns, reflecting histological changes when the latter is inv aded by tumour cells. Liver, kidney, spleen and blood porphyrins also raise d from basal levels, showing that ALA and/or ALA-induced porphyrins reach a ll tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faece s. ALA lotion applied on the skin overlying the tumour induced higher accum ulation of tumoural porphyrins than cream, and lotion applied on normal ski n appeared to be the most efficient upon inducing total body porphyrins. Th is work has demonstrated the great influence of the formulation of ALA vehi cle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours.