Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin

• Published in: PloS one Vol. 11; no. 2; p. e0148850
• Main Authors: de Bruijn, Henriëtte S, Brooks, Sander, van der Ploeg-van den Heuvel, Angélique, Ten Hagen, Timo L M, de Haas, Ellen R M, Robinson, Dominic J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.02.2016; Public Library of Science (PLoS)
• Subjects: Acids; Aminolevulinic acid; Aminolevulinic Acid - analogs & derivatives; Aminolevulinic Acid - pharmacokinetics; Aminolevulinic Acid - pharmacology; Animal models; Animals; Animals, Outbred Strains; Antineoplastic agents; Basal cell carcinoma; Biology and Life Sciences; Cadherins; Care and treatment; Cervix; Clinical trials; Dermatology; Dose Fractionation, Radiation; Drug Evaluation, Preclinical; Drug synergism; Effectiveness; Endothelial Cells - metabolism; Female; Fluorescence; Fluorescence microscopy; Formulations; Fractionation; Gynecology; Hairless; Illumination; Keratosis; Light; Medicine and Health Sciences; Methods; Mice; Microscopy, Fluorescence; Nanoemulsions; Observations; Oral squamous cell carcinoma; Otolaryngology; Photobleaching; Photochemotherapy; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Physical Sciences; Protoporphyrin; Protoporphyrin IX; Protoporphyrins - pharmacokinetics; Research and Analysis Methods; Skin; Skin - blood supply; Skin - drug effects; Skin - metabolism; Skin cancer; Spatial distribution; Squamous cell carcinoma; Studies; Surgery; Sus scrofa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148850

Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models. In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination. The present study illustrates the clinical potential of light fractionated PDT using BF-200 ALA for enhancing PDT efficacy in (pre-) malignant skin conditions such as basal cell carcinoma and vulval intraepithelial neoplasia and its application in other lesion such as cervical intraepithelial neoplasia and oral squamous cell carcinoma where current approaches have limited efficacy.