A dynamic model for ALA-PDT of skin: simulation of temporal and spatial distributions of ground-state oxygen, photosensitizer and singlet oxygen.

摘要

Singlet oxygen (1O2) 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 1O2 distribution and cumulative [Formula: see text] 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 (3O2) and 1O2 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, 1O2-mediated photobleaching mechanism for updating PpIX, 3O2 and 1O2 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 1O2-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, 3O2 and 1O2 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.