Photodynamic Therapy (PDT) is a powerful technique that is combined with radiation therapy and chemotherapy for the treatment of several types of cancer that occur within 1 cm of an organ’s surface or near the skin. One of the significant effects of this relatively new technique is its fast action, with tumor ablation often occurring within a few days. PDT uses light, generally from a laser, to generate singlet oxygen to kill malignant cells. Singlet oxygen is a highly reactive, cytotoxic form of molecular oxygen.

The treatment begins when a photosensitizing drug is injected into the bloodstream and cells throughout the body selectively absorb the active agent. After a period of time, which varies with the photosensitizer localization properties, the retention of the drug within tumor cells is substantially greater compared to the levels in normal tissue. However, the window of opportunity is small, so treatment must begin promptly. For activation of the photosensitizer, the tumor region is illuminated with a laser whose emission wavelength coincides with the photosensitizer absorption peak.

Absorption of light by the tumor-bound photosensitizer in the presence of molecular oxygen initiates a cascade of molecular chemical or charged events that results in the death of the malignant cells.

Advantages of PDT over other techniques are:
 

• A degree of selectivity of drug binding to tumor tissue
• The absence of systemic toxicity of the drug alone
• Ability to focus the light on the tumor region
• The possibility of treating multiple lesions simultaneously and
• The ability to retreat a tumor to improve the overall response

Disadvantages of PDT have been shown to be the prolonged skin photosensitivity, at least for the first generation drug Photofrin®, limited depth of penetration of light (generally only up to 1 cm), and the inability to treat widely disseminated disease.

The PDT Center in the Department of Radiation Oncology, University Hospitals Case Medical Center has been involved in several treatment protocols using Photofrin (a first generation photosensitizer) and Pc 4 (a second generation photosensitizer).

Pc 4, silicon phthalocyanine, was developed at Case Western Reserve University and University Hospitals Case Medical Center and is currently in Phase I-II clinical trial. These trials are designed to test the efficacy of this translational research effort first demonstrated in mice and now used to treat superficial human cancers. The desirable properties of Pc 4 are its chemical purity, its high extinction coefficient, and its rapid clearance from skin that helps limit treatment complications related to the extent and duration of cutaneous photosensitivity.