PpIX Fluorescence Kinetics and Increased Skin Damage after Intracutaneous Injection of 5-Aminolevulinic Acid and Repeated Illumination

Abstract

Photodynamic therapy with topically applied 5-aminolevulinic acid is used successfully for superficial skin lesions. The results for thicker, nodular lesions are less favorable. The method of aminolevulinic acid administration, the concentrations of aminolevulinic acid, and the irradiation schemes used so far have not been investigated thoroughly. As aminolevulinic acid photodynamic therapy has high potential for the increasing problem of skin cancer, we investigated both visually and histopathologically the photodynamic-therapy-induced skin damage after intracutaneous administration of aminolevulinic acid in normal porcine skin. We also investigated the kinetics of the aminolevulinic-acid-induced photosensitizer protoporphyrin IX fluorescence after irradiation in relation to fluence and irradiance. Finally we investigated the effect on photodynamic-therapy-induced damage of a fractionated irradiation. This study demonstrates that intracutaneous administration of aminolevulinic acid leads to higher fluorescence levels and thus to formation of higher protoporphyrin IX concentrations than topical application of aminolevulinic acid cream. The peak level of protoporphyrin IX after intracutaneous administration of aminolevulinic acid is reached earlier than after topical administration. The comeback of fluorescence, indicating re-synthesis of protoporphyrin IX after irradiation, is inhibited with increasing fluence. Photodynamic-therapy-induced damage increases with increasing fluence, but is independent of the irradiance. Finally, the photodynamic-therapy-induced skin damage seems to be greater after fractionated irradiations with two equal light fractions of 15 J per cm2 separated by a dark interval of 2 h.

Intracutaneous ALA photodynamic therapy: Dose-dependent targeting of skin structures

“…In this study, we observed that injections of even very low concentrations of ALA solution could induce porphyrin accumulation, down to and including 0.0005%. With ALA concentrations ≤0.002%, porphyrin fluorescence was limited to the area where the drug was injected (2–4 mm deep), similar to a previous observation of Thissen et al 33. Localization of low‐concentration ALA at the depth of injection may explain why porphyrin fluorescence was localized only in superficial fat at these concentrations, but does not explain the inverse concentration dependence for damage to fat by injected ALA‐PDT.…”

Topical 5-Aminolevulinic Acid Mediated Photodynamic Therapy of Superficial Basal Cell Carcinoma Using Two Light Fractions with a Two-hour Interval: Long-term Follow-up

“…The re-synthesis of PpIX suggested the application of a second illumination, a few hours after the first, in the hope of increasing the effectiveness of ALA-PDT. Increased efficacy of ALA-PDT by fractionated illumination with intervals between 75 min and 6 h was indeed demonstrated in several animal models: first, using systemically administered ALA, on tumour and normal rat skin in the window chamber model (16) and on subcutaneous tumours in the flank of rats (19); secondly, using topically applied ALA on normal and UVB-treated hairless mouse skin (18,20,21); and thirdly, using locally injected ALA on normal pigskin (22). In the present paper we show clinical results for the treatment of sBCC using topically applied ALA and two light fractions with a 2-h interval.…”

Single vs. fractionated photodynamic therapy for face and scalp actinic keratoses: a randomized, intraindividual comparison trial with 12‐month follow‐up

“…The mechanism behind this increased efficacy is unclear. Suggested hypotheses include improved oxygenation of the illuminated tissue, which theoretically can lead to the generation of more singlet oxygen and thus enhance the response to therapy 16 as well as the utilization of resynthesized protoporphyrin IX during the second‐light fraction after photobleaching during the first‐light fraction. It seems, however, that the amount of resynthesized protoporphyrin does not correlate with the response to the treatment.…”