Daylight Photodynamic Therapy: An Update

Abstract

Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves.

Keywords: actinic keratosis; aminolevulinic acid; daylight; history; nonmelanoma skin cancer; photodynamic therapy.

Figure 1

The mechanism of daylight photodynamic therapy. After daylight absorption, the photosensitizer (PS, 5-aminolevulinic acid (5-ALA), a prodrug of the real PS protoporphyrin IX, is exemplified here) is excited to a singlet state and undergoes intersystem crossing to the excited triplet-state. The triplet excited PS can react in two ways: a Type I reaction which involves the generation of superoxide anion radical (O₂^•−), hydrogen peroxide (H₂O₂), and hydroxyl radical (OH^•) by electron transfer to molecular oxygen, and/or by the type II reaction through energy transfer to generate singlet oxygen (¹O2). PS: photosensitizer; ¹PS*: excited singlet state, ³PS* excited triplet state.

Figure 2

The wavelength of light determines an optimal therapeutic window of photodynamic therapy. (a) The absorption peaks of protoporphyrin IX (black) and sunlight spectrum (brown). (b) The relationship between wavelengths of light and skin penetration depth.

Figure 3

History of photodynamic therapy.

Figure 4

The cross-talk of glucose, glutamine and porphyrin heme biosynthesis pathways. In addition to porphyrin synthesis via the tricarboxylic cycle acid (TCA) cycle, the accumulation of PpIX in tumor cells might be explained by an increase of glycolysis (in blue) and glutaminolysis (in red). Modified from reference 24.

Figure 5

Clinical pictures of actinic keratosis (AK). (a) An erythematous AK locates on sun-damaged skin in an elderly patient. (b) A thick keratotic AK on the scalp of the same patient. In a thick AK, the hyperkeratotic skin surface prevents sufficient transdermal delivery of a photosensitizer for photodynamic therapy. The rough surface is usually removed by curettage before the application of a photosensitizer. AK lesions are highlighted by circles.

Figure 6

dPDT treatment on an elderly chronic arsenism patient with multiple Bowen’s diseases (BDs). (a) One BD on the left upper arm was marked to show the drug application area. (b) To improve the transdermal delivery of the photosensitizer, the lesion was occluded for one hour after being slightly curetted. A vivid pink fluorescence of PpIX was well localized within the tumor under Wood’s lamp examination. (c) The lesion was clinically clear after one treatment of 2 h of exposure to sunlight. No recurrence was noted one year after dPDT.