Llew Keltner

New technology for deep light distribution in tissue for phototherapy.

Photodynamic therapy is one of several techniques developed for phototherapy for solid cancers and hematologic malignancies. Photodynamic therapy is a treatment that utilizes a molecular energy exchange between visible light and a photosensitive drug, which results in the production of 1O2, a highly reactive cytocidal oxygen species. The effect is limited to the region where light and drug are combined so that malignant tissue is destroyed and the usual side effects associated with standard cancer therapies are avoided.The light component of photodynamic therapy is customarily generated via dye-pumped or diode lasers. The cost and the complexity of lasers have seriously limited the clinical use of photodynamic therapy for malignancies. A new device technology, based on light-emitting diodes, has been developed (Light Sciences Corporation, Issaquah, WA) that allows light production inside the target tissue. This new technology will expand the current range of indications that are treatable with photodynamic therapy to include moderate-and large-volume refractory tumors.Conventional photodynamic therapy utilizes the delivery of intense light for seconds or minutes. The new approach differs from conventional photodynamic therapy in that it combines a novel interstitial light delivery system with prolonged photoactivation of photosensitive drugs. Prolonging photoactivation time in order to deliver a higher light dose results in an amplification effect, whereby the repeated activation of each photosensitive drug molecule leads to the generation of many thousands of 1O2 molecules. The production of overwhelming numbers of these powerful oxidants in individual cells and the vascular supply of tumors leads to irreversible damage and death of the targeted lesions. Results of preclinical studies have indicated a significant correlation between increased duration of photoactivation and increased volume and depth of photodynamic therapy-induced necrosis.The new developments will enable photodynamic therapy to be used effectively against refractory bulky disease as frontline therapy or in combination with chemotherapy, radiation therapy, or biologics. Perhaps most promising, many patients with advanced refractory disease may now be relieved of symptoms or may return to the treatable population.