Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.

Photodynamic therapy (PDT) is a treatment modality that utilizes a photosensitizing drug activated by laser generated light, and is proving effective for oncologic and nononcologic applications. This report provides an overview of photosensitizers, photochemistry, photobiology, and the lasers involved in photodynamic therapy. Clinical and preclinical PDT studies involving Photofrin and various second generation photosensitizers are reviewed.

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Improvements in PDT tumor responsiveness may be achieved by employing combined modality regimens targeting malignant cells as well as treatment-induced angiogenesis and/or inflammation.