The effect of light fractionation with a 2-h dark interval on the efficacy of topical hexyl-aminolevulinate photodynamic therapy in normal mouse skin

摘要

Background: Light fractionation with a 2-h dark interval increases the efficacy of topical aminolevulinic acid (ALA) photodynamic therapy (PDT). Hexyl-aminolevulinate (HAL) is the hexyl ester of ALA. Both HAL and ALA lead to protoporphyrin IX (PplX) accumulation in endothe-lial cells and to vascular effects, which are important for light fractionation. We investigated light fractionation for HAL-PDT in a mouse skin model and compared this with ALA. Methods: Three illumination schemes were studied: (a) 100 Jcm~2 in a single illumination; (b) 50 + 50 Jcm~(-2) in a twofold illumination; (c) a small first light fraction until 50% of PplX was photobleached (ca. 3 Jcm~(-2)), followed by 97Jcm~(-2) 2h later. PplX fluorescence was measured continuously during illumination. Efficacy was evaluated by daily visual skin damage scoring up to 7 days after PDT. Results: Light fractionation showed a trend towards increased efficacy for HAL-PDT. Both the initial PplX synthesis and the PplX resynthesis during the dark interval were higher for ALA, but these were not correlated with efficacy. Single HAL-PDT was more effective than single ALA-PDT. Photobleaching rates of HAL and ALA were similar indicating similar biodistributions at depth. Conclusion: Our results provide evidence to support that light fractionation may be beneficial for HAL-PDT. We are cautious because we found only a non-significant increase in response. However, combining our results with literature data suggest that the illumination scheme may be further optimized for HAL-PDT to potentially enhance the effect of light fractionation.