CHEMICAL MODIFICATION OF NORMAL TISSUE-DAMAGE INDUCED BY PHOTODYNAMICTHERAPY

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensit ivity. This paper describes results of experiments designed to test th e effects of two radiation protective agents (WR-2721, 500 mg kg(-1) o r WR-3689, 700 mg kg(-1)) on murine skin damage induced by PDT. C3H mi ce were shaved and depilated three days prior to injection with the ph otosensitiser, Photofrin (5 or 10 mgkg(-1)). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 mm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A li ght dose response as well as a drug dose response was obtained. The re sults indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg(-1)), and 630 nm light (180 J cm(-2)) pretreatment with either WR-2 721 or WR-3689 resulted in significant protection of the vascular effe cts of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light o n photosensitized skin. They do so in a drug dose-dependent fashion wi th maximum protection at the highest drug doses.