Therapy Center, Roswell Park Cancer Institute, Buffalo, NY; C. J. Gomer,. Clayton Ocular ...... Donington (182) at the National Institute of Health pioneered the.
REVIEW Photodynamic Therapy Thomas J. Dougherty, Charles J. Gomer, Barbara W. Henderson, Giulio Jori, David Kessel, Mladen Korbelik, Johan Moan, Qian Peng*
Photodynamic therapy involves administration of a tumorlocalizing 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 (Photofrint) 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. [J Natl Cancer Inst 1998;90:889–905]
Background Photochemotherapy of cancer is often called ‘‘photodynamic therapy (PDT).’’ The term ‘‘photodynamic action’’ (1) is used to distinguish photosensitized reactions in biology from the physicochemical processes occurring in the emulsions of photographic films. Blum (2) suggested that this definition should be applied only to photochemical reactions in which oxygen was consumed. Such reactions are also called photosensitized processes of type I and type II depending on the nature of the primary steps, namely, the initial involvement of radical intermediates that are subsequently scavenged by oxygen or the generation of the highly cytotoxic singlet oxygen (1O2) by energy transfer from the photoexcited sensitizer. 1O2 has a short lifetime in biologic systems (
