Abstract
Singlet oxygen 
direct dosimetry and photosensitizer fluorescence photobleaching are being investigated and applied as dosimetric tools during 5-aminolevulinic acid (ALA)-induced protophorphyrin IX (PpIX) photodynamic therapy (PDT) of normal skin and skin cancers. The correlations of photosensitizer fluorescence and singlet oxygen luminescence (SOL) emission signals to 
distribution and cumulative 
dose are difficult to interpret because of the temporal and spatial variations of three essential components (light fluence rate, photosensitizer concentration and oxygen concentration) in PDT. A one-dimensional model is proposed in this paper to simulate the dynamic process of ALA-PDT of normal human skin in order to investigate the time-resolved evolution of PpIX, ground-state oxygen 
and 
distributions. The model incorporates a simplified three-layer semi-infinite skin tissue, Monte Carlo simulations of excitation light fluence and both PpIX fluorescence and SOL emission signals reaching the skin surface, 
-mediated photobleaching mechanism for updating PpIX, 
and 
distributions after the delivery of each light dose increment, ground-state oxygen supply by diffusion from the atmosphere and perfusion from blood vessels, a cumulative 
-dependent threshold vascular response, and the initial non-uniform distribution of PpIX. The PpIX fluorescence simulated using this model is compared with clinical data reported by Cottrell et al (2008 Clin. Cancer Res. 14 4475–83) for a range of irradiances (10–150 mW cm−2). Except for the vascular response, one set of parameters is used to fit data at all irradiances. The time-resolved depth-dependent distributions of PpIX, 
and 
at representative irradiances are presented and discussed in this paper, as well as the PDT-induced vascular response at different depths. Tissue hypoxia and shutdown of oxygen supply occur in the upper dermis, where PpIX is also preserved at the end of treatment.
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General scientific summary. During photodynamic therapy (PDT) of skin diseases it is possible to measure the fluorescence from the photosensitizing drug and the phosphorescence from excited (singlet) oxygen molecules. There is considerable interest in using these signals to optimize PDT dosimetry but their interpretation is complicated by temporal and spatial variations of light fluence rate, photosensitizer concentration and oxygen concentration. To help understand these signals and PDT dosimetry in general, we have developed a dynamic model of PDT of skin. It incorporates the layered structure of skin, Monte Carlo simulations of light propagation, the major photochemical reactions, and oxygen delivery, consumption and diffusion. When the model uses input parameters from the literature, the calculated fluorescence agrees with clinical data published by other researchers. Detailed examination of the depth distribution of oxygen, singlet oxygen and photosensitizer reveals interesting features that may be important in understanding PDT response.