DOSIMETRY MODEL FOR PHOTODYNAMIC THERAPY WITH TOPICALLY ADMINISTERED PHOTOSENSITIZERS

Background and Objective: Photodynamic therapy (PDT) based on topical application of photosensitizers has been under development over the la st years. Typical applications are treatment of basal cell carcinoma o f the skin and photoablation of the endometrium. The dosimetry for top ically administered photosensitizers must take a time-dependent inhomo genous drug distribution into account together with the conventional p arameters such as optical scattering, absorption, and photobleaching. Study Design/Materials and Methods: This study presents a dosimetry mo del where the cytotoxic dose is calculated in a stepwise procedure. Th e first step calculates the time-dependent distribution of 5-aminolevu linic acid (5-ALA) from diffusion theory. In skin this distribution is dependent on drug permeability through the stratum corneum, on the di ffusivity of dermis and epidermis, on the drug clearance time, and on the conversion rate from 5-ALA to protoporphyrin IX (PpIX). In the sec ond step the distribution of PpIX is calculated from the 5-ALA distrib ution found in the first step taking the dynamics of the biosynthesis of 5-ALA to PpIX and the clearance time of PpIX into account. In the t hird step the generation of cytotoxic singlet oxygen is calculated fro m the optical distribution during irradiation, taking a photobleaching mechanism into account. Results: The distribution of cytotoxic oxygen is predicted from the optical dose, the drug dose, and the time betwe en the application of the drug and the irradiation. Conclusion: The pr esented dosimetry model is made as simple as possible, yet composite e nough to enable all relevant parameters to be taken into account. The model that is based on a linear theory in a semi-infinite medium can, if required, be extended to take nonuniform and nonlinear phenomena in to account. (C) 1996 Wiley-Liss, Inc.