Photodynamic therapy with aminolevulinic acid or its methyl ester: Which one is superior?

Abstract

Abstract Aminolevulinic acid (ALA), as precursor of the potent photosensitizer protoporphyrin IX (PpIX) in the heme biocycle, generates PpIX in excess, if it is given externally to cells. During photodynamic therapy with ALA (ALA-PDT) the accumulated PpIX – irradiated with red light of a wavelength of 635 nm in the presence of oxygen – produces reactive oxygen species which destroy the target tissue. The most common side effect of ALA-PDT is pain, burning or stinging discomfort at the site of treatment. Due to the relatively low bioavailability of the ALA molecule, ester derivatives have been designed with aliphatic side chains of different length. As soon as ALA esters are taken up by the cell, they are hydrolyzed to the active form by enzymes and processed in the same way as ALA. ALA or methyl aminolevulinate (MAL or ALA-methyl ester) can be used for a variety of diseases not only for photodynamic treatment, but also very effectively for fluorescence diagnosis. Several advantages of MAL over ALA have been reported, such as facilitated crossing of the stratum corneum and cell membranes, higher selectivity (e.g. in solar keratoses), increased PpIX formation leading to higher fluorescence and photodynamic efficiency, less pain, fewer systemic effects after local treatment, and faster clearance from the cells. The lack of systemic effects after topical MAL-PDT, higher fluorescence after MAL application and the higher selectivity of MAL-PDT have all been scientifically confirmed. ALA has been approved as Levulan ® for actinic keratosis (EU, US) and MAL as Metvix ® or Metvixia ® for actinic keratosis (EU, US), basal cell carcinoma and Bowen's disease (EU).