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Throughout the 20th century, scientists explored the use of photodynamic therapy (PDT) in medicine. PDT is a photochemical reaction in which a photosensitizing molecule, a light source, and tissue oxygen interact to produce targeted tissue destruction. Although PDT was initially thought to have great potential, its clinical use was postponed by worries of prolonged retention of the photosensitizer. By the late 20th century, 5-aminolevulinic acid (ALA) was shown to convert itself into an effective photosensitizing molecule, namely, protophorphyrin IX, in targeted tissue while also having a reasonable period of tissue retention.1 This work paved the way for dermatologic applications. Topical PDT lends itself well to cutaneous disease because of the ease of application of a photosensitizer and delivery of light. In 1999, the Food and Drug Administration (FDA) approved the use of topical ALA and blue light for the treatment of actinic keratoses (AK), and its list of on- and off-label indications has since continued to expand.


In PDT, the photosensitizing molecule absorbs photon energy from a light source. That energy bumps a stably orbiting electron into an excited state. The excited states are transient, but during this state tissue interaction is possible. Excited porphyrins are known to interact with tissue oxygen, producing singlet oxygen species and, in turn, intense oxidative damage. Ultimately, there is cell death, vascular injury, inflammation, and immunologic responses. Porphyrins are commonly used photosensitizers in dermatologic practice because of this interaction with oxygen.

PDT photosensitizers can be delivered systemically (oral or intravenous), topically, and intralesionally. Systemic delivery is necessary when large-molecular-weight photosensitizers are used that do not penetrate the stratum corneum. They are often transported throughout the body bound to low-density lipoprotein (LDL) and gain entry into target tissue via LDL receptors. Photosensitizers, such as the commonly used ALA and methyl-esterified ALA (MAL), can be delivered topically because of their relatively low molecular weight and ability to penetrate into the epidermis. ALA and MAL subsequently convert into the photosensitive protoporphyrin IX (PpIX) as part of the porphyrin biosynthetic pathway. MAL represents an esterified form of ALA that is more lipophilic and therefore may penetrate more deeply into the skin. In addition, MAL has been shown to have greater selectivity than ALA for cells in lesional skin of AK2 and acne.3 As the cellular uptake mechanisms for these agents differ, the intensity of pain may be lower during PDT using MAL than that using ALA.

Both light- and laser-based systems can be used to activate PDT. Whatever source is selected, the chosen wavelength or wavelengths are between 400 and 800 nm for several reasons. These wavelengths avoid the carcinogenic effect of ultraviolet (UV) light (<400 nm), can deliver enough photon energy, and cover the absorption peaks of the porphyrin photosensitizers.

The treatment parameters in PDT notably include light dose. The light dose is ...

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