Pretreatment to Enhance Protoporphyrin IX Accumulation in Photodynamic Therapy

• Published in: Dermatology (Basel) Vol. 218; no. 3; pp. 193 - 202
• Main Authors: Gerritsen, M.J.P., Smits, T., Kleinpenning, M.M., van de Kerkhof, P.C.M., van Erp, P.E.J.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2009; S. Karger AG
• Subjects: Aminolevulinic Acid - analogs & derivatives; Aminolevulinic Acid - pharmacology; Animals; Biological and medical sciences; Dermatology; Diseases of the skin. Cosmetics; Humans; Keratosis - metabolism; Medical procedures; Medical sciences; Pharmaceuticals; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacology; Protoporphyrins - metabolism; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Review; Skin - drug effects; Skin - metabolism; Skin diseases; Literature review; Photodynamic therapy; Adjuvant treatment; Protoporphyrin; Dermatology; Pretreatment; Accumulation; Bibliographic review
• ISSN: 1018-8665; 1421-9832
• DOI: 10.1159/000183753

The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an important negative factor in ALA uptake. This review has its focus on pretreatment of the skin in order to improve the clinical outcome of ALA/MAL PDT. Pretreatment of hyperkeratosis can be achieved with keratolytics, curettage/debulking, tape stripping, microdermabrasion or laser ablation. Penetration enhancers may alter the composition or organization of the intercellular lipids of the stratum corneum. Several studies have been performed on the use of dimethyl sulfoxide, azone, glycolic acid, oleic acid and iontophoresis to increase the penetration of ALA. As PpIX production is also dominated by temperature-dependent processes, elevating skin temperature during ALA application may also improve treatment results. Another approach is the use of additives that interact with the heme biosynthetic pathway, e.g. by removing ferrous iron with iron-chelating substances such as: ethylenediaminetetraacetic acid; 3-hydroxypyridin-4-ones; 1,2-diethyl-3-hydroxypyridin-4-one-hydrochloride; and desferrioxamine. In conclusion, simple pretreatments or additions to the regular practice of PDT, aimed to optimize intralesional PpIX content, improve the clinical outcome.