Photodynamic therapy in oncology: mechanisms and clinical use.
In photodynamic therapy (PDT), a sensitizer, light, and oxygen are used to cause photochemically induced cell death. The mechanism of cytotoxicity involves generation of singlet oxygen and other free radicals when the light-excited sensitizer loses or accepts an electron. Although selective retention of sensitizer by malignant tissue is seen in vivo, the mechanisms for this sensitizer targeting remain unclear. The first-generation sensitizers are porphyrin based and vary in lipophilicity and hydrophilicity. Targeting of the vasculature seems to be a prominent feature of the cytotoxic effect of these sensitizers in vivo, with resulting necrosis. Treatment depth varies with the wavelength of light that activates the sensitizer used, and the second-generation sensitizers are activated at longer wavelengths, allowing for a 30% increase in treatment depths. The selectivity of targeting can be increased when the sensitizer is delivered with the use of liposomes or monoclonal antibodies specific for tumor antigens. Studies have demonstrated direct effects of PDT on immune effector cells, specifically those with lineage from macrophages or other monocytes. Clinically, this therapy has been chiefly used for palliation of endobronchial and esophageal obstruction, as well as for treatment of bladder carcinomas, skin malignancies, and brain tumors. The future of PDT rests in defining its use either as an intraoperative adjuvant to marginal surgical procedures or as a primary treatment for superficial malignancies. Phase III trials in esophageal cancer and lung cancer are in progress and will help in evaluation of whether Photofrin II, the most widely used sensitizer, can be added to the oncologic armamentarium, pending approval from the U.S. Food and Drug Administration.
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Thoracic Oncology Section, NCI/NIH, Bethesda, MD 20892.
D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D054833:Isoindoles; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy; D011166:Porphyrins / Q000627:therapeutic use
D007211:Indoles; D054833:Isoindoles; D011166:Porphyrins; C006969:chlorin; D017323:Dihematoporphyrin Ether; C013647:phthalocyanine