The Application of Photofrin II® as a Sensitizing Agent for Ionizing Radiation-A New Approach in Tumor Therapy?

M.      Schaffer; B.      Ertl-Wagner; P.   M.   Schaffer; U.      Kulka; G.      Jori; E.      Duhmke; A.      Hofstetter

Abstract

Radiosensitizers represent an enticing concept in tumor therapy. As ionizing radiation affects both neoplastic and normal tissues, its effects are generally non-specific. The aim of applying a radiosensitizing agent is to achieve a maximum effect on tumor tissue, while minimizing the damage to normal tissues. A variety of parameters such as the oxygen supply and the state in the cell cycle, need to be taken into account when evaluating a potential radiosensitizer. Most of the previously known radiosensitizers are neither selective nor tumor specific. In this article, we review the properties and radiosensitizing potential of Photofrin II® . Photofrin II® is wellknown as a photosensitizing agent in photodynamic therapy. In recent years, a radiosensitizing potential of the substance has been demonstrated, specifically increasing the sensitivity of solid tumor tissues, especially of radio-resistant, hypoxic tumor cells, to radiation. This radiosensitizing effect has been demonstrated both by in vitro studies and by animal experiments. Several studies with tissue cultures have demonstrated a radiosensitizing effect of Photofrin II® in glioblastoma (U-373MG) and bladder cancer cell lines (RT-4). No effect was noted in colon carcinoma cell lines (HT-29). Unpublished data of additional cell lines will be mentioned in the review. Animal experiments with Lewis sarcoma and with bladder cancer have moreover demonstrated an in vivo effect of Photofrin II® as a radiosensitizer. The mechanism of this radiosensitizing effect is not completely understood. In vitro data, however, support the hypothesis that the radiosensitizing action involves OH-radicals in addition to a potential impairment of repair mechanisms after sublethal damage of ionizing radiation. Moreover, early results of a phase I trial are available and document the potential feasibility of the application of Phototofrin II® as a radiosensitizing agent in clinical practice.

Keywords: porphyrins, radiosensitization, photosensitization, radiation therapy

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