title: A dynamic model for ALA-PDT of skin: simulation of temporal and spatial distributions of ground-state oxygen, photosensitizer and singlet oxygen.
abstract: 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 ¹O₂dose 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 (³O₂and 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.
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada. Baochang.Liu@jcc.hhsc.ca
authors.forename: Baochang
authors.initials: B
authors.lastname: Liu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Farrell
authors.forename: Michael S
authors.initials: MS
authors.lastname: Patterson
mesh_terms: D000622:Aminolevulinic Acid / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009010:Monte Carlo Method; D010100:Oxygen / Q000378:metabolism*; D038761:Photobleaching; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000494:pharmacology; D011355:Prodrugs / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism / Q000494:pharmacology; D026082:Singlet Oxygen / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D026082:Singlet Oxygen; D000622:Aminolevulinic Acid; D010100:Oxygen