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Photodynamic therapy (PDT) is increasingly used in both USA and Europe for the treatment of actinic keratosis (AK) and selected cases of nonmelanoma skin cancer (NMSC). Being a minimally invasive therapy, PDT is especially suitable for the treatment of multiple lesions, field cancerization and lesions located in areas where optimal cosmetic outcome is essential.1,2 The principle of PDT involves the combination of a photosensitizer, oxygen, and light to produce selective cytotoxic damage of dysplastic cells. In dermatology, PDT is used with a topically applied photosensitizer, which allows for specific lesion targeting.

Topical PDT was introduced in 1990 when Kennedy and Pottiers applied 5-aminolevulinic acid (ALA), a precursor of the endogenous photosensitizer, protoporphyrin IX (PpIX), directly on skin tumors.3,4 The use of a topically applied photosensitizer was a major advantage compared to the previously used photosensitizers, which required intravenous administration and produced long-lasting phototoxicity.5 Since the introduction of PDT with ALA or its methylated ester, methyl aminolevulinate (MAL), intensive research has established PDT in dermatology and the concept of PDT is now substantially documented for the treatment of NMSC and precursor lesions. PDT is performed with both ALA and MAL for AK lesions and besides, MAL-PDT is approved in Europe for the treatment of Bowen’s disease (BD, squamous cell carcinoma [SCC] in situ), and superficial and small nodular basal cell carcinomas (BCC).1,2 Furthermore, PDT is administered as off-label treatment for photoaged skin, acne, and selected skin conditions of inflammatory, infectious, and neoplastic origin.

Mechanisms of Photodynamic Therapy

The mechanism of PDT involves the simultaneous presence of a photosensitizer, oxygen, and light. A photosensitizer is a molecule that absorbs light of appropriate wavelengths to initiate a photochemical reaction.6 When a photosensitizer absorbs light, an electron is transferred to a higher energy orbital and the photosensitizer enters the excited singlet state (Fig. 33-1).7 The excited singlet state is very unstable and thus, the photosensitizer emits excess energy as either fluorescence and/or heat, or undergoes intersystem crossing to form a more stable excited triplet state (Fig. 33-1).7 From the triplet state, PpIX can either (i) decay to the ground state, (ii) react directly with the substrate to form free radicals (type I reaction), or (iii) react directly with tissue oxygen to form singlet oxygen (1O2) (type II reaction).8

The main mechanism of action in PDT is the type II reaction, in which the excited PpIX reacts with molecular oxygen to form 1O2.7,9 1O2 is highly unstable and reacts with nearby molecules, including PpIX itself, causing cellular damage and ultimately cell death.10 During type I and II reactions, PpIX itself is degraded by a process known as photobleaching, which is useful ...

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