Optimum porphyrin accumulation in epithelial skin tumours and psoriatic lesions after topical application of δ-aminolaevulinic acid

Abstract

Photodynamic therapy with topically applied δ-aminolaevulinic acid is used to treat skin tumours by employing endogenously formed porphyrins as photosensitizers. This study examines the time course of porphyrin metabolite formation after topical application of δ-aminolaevulinic acid. Porphyrin biosynthesis in human skin tumours (basal cell carcinoma, squamous cell carcinoma), in psoriatic lesions, and in normal skin was investigated. Skin areas were treated with δ-aminolaevulinic acid, and levels of total porphyrins, porphyrin metabolites and proteins were measured in samples excised after 1, 2, 4, 6, 9, 12 and 24 h. There was an increase in porphyrin biosynthesis in all tissues with maximum porphyrin levels in tumours between 2 and 6 h and in psoriatic lesions 6 h after treatment. The pattern of porphyrins showed no significant difference between normal and neoplastic skin, protoporphyrin being the predominant metabolite. The results suggest that optimum irradiation time for superficial epithelial skin tumours may be as soon as 2 h after application of δ-aminolaevulinic acid, whereas for treatment of psoriatic lesions an application time of 6 h is more suitable. © 1999 Cancer Research Campaign

Development of a handheld fluorescence imaging device to investigate the characteristics of protoporphyrin IX fluorescence in healthy and diseased skin

“…One of the causes of incomplete response or recurrence to PDT may be insufficient accumulation of PpIX throughout the diseased tissue 11,12,13 . An optimal concentration of PpIX after application of ALA as pro-drug has been reported to be at six hours and with the full incubation period being 24 hours in that study 14 . PpIX concentration increases and reaches a plateau in both BCC and AK lesions after 13 hours of continuous application of MAL cream 15 .…”

“…However, the recommended time to start the treatment is 3 hours 1,2 . Yet, there is a limited information about PpIX metabolism at shorter periods of time 14,15,16 . Our work aims to develop improved instrumentation for detecting PpIX and apply it to filling these gaps in the knowledge about PpIX building-up during the first three hours from the application of the topical pro-drug.…”

Design and validation of a fiber optic point probe instrument for therapy guidance and monitoring

“…6, generally very realistic quantification results have been achieved in terms of a higher blood content and higher PpIX concentration for the tumor lesions than the normal skin. The obtained [PpIX] is consistent with the values reported for various human skin malignancies with topically applied ALA. 34 Such clusters could be used for tissue classification purposes. However, one location for normal skin was predicted to have a much higher μ 0 s ð635Þ (>30 cm −1 ) than the others, which is obviously not likely to be true.…”

“…33 For ALA-mediated skin PDT, topical application of ALA was reported to result in a PpIX concentration of 1 to 2 μm for various human skin malignancies. 34 Due to the high fluorophore sensitivity of our system, it is possible to reduce the ALA dose for intracranial tumor fluorescence purposes (commonly used at 20 mg∕kg body weight 21 ), and thus minimize the adverse side effects in patients undergoing surgery and avoid affecting normal brain. Owing to the higher photosensitivity of APD, it is also possible to reduce the power of the excitation light in order for less fluorophore photobleaching, which could perturb the optical diagnostics.…”

Investigation of the effect of low power laser used in photodynamic therapy for treatment of psoriasis

“…With regard to short-contact ALA in epithelial skin tumors and psoriatic lesions, another study by Fritsch et al [12] showed that a maximum concentration of ALA in the tumors and psoriatic skin was reached between 2 and 6 h. …”