INTRODUCTION

Clinical applications of photodynamic therapy (PDT) have expanded over the last several years due to new light sources and FDA approved photosensitizers. Compared to surgery and radiation therapy for nonmelanoma skin cancers, PDT has many potential advantages. A single, noninvasive session can treat simultaneously multiple areas as well as extensive superficial lesions. Repeated sessions can be performed without total dose limitations. PDT is generally associated with good patient tolerance, relatively short healing time, and overall good cosmesis. It can be carried out in nonsurgical candidates and can occasionally be combined with other therapeutic modalities (Table 45.1).

MECHANISMS OF ACTION

PDT is a three-component process involving a photosensitizing drug, light, and molecular oxygen. Light absorption by the photosensitizer produces an excited triplet state, which transfers its energy to oxygen, forming highly reactive, cytotoxic singlet oxygen that can also generate other reactive oxygen species and free radicals. The photosensitizer then can absorb another photon and repeat the process, generating multiple molecules of singlet oxygen until the photosensitizer is destroyed (photobleached) by autooxidation. The singlet oxygen and other free radicals produced by PDT directly kill cells through apoptosis and necrosis, and also activate both innate and adaptive host responses through the release of inflammatory and immune mediators. In addition, systemic PDT with exogenous photosensitizers can cause shutdown of tumor microvasculature with resulting oxygen and nutritional starvation of tumor and normal tissue cells fed by the vessels.

LIGHT

Light sources available for PDT include laser and nonlaser sources.