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.