Photodynamic therapy (PDT) is a minimally-invasive technique whose usefulness in treating tumors has been limited by the inability of short wavelength light (e.g., usually ultraviolet) to deeply penetrate into tissue. Two-photon laser-induced PDT is proposed which will improve the depth of penetration into soft tissue and provide precise spatial control. Two-photon excitation will be effected using a mode-locked titanium-sapphire laser (76 MHZ pulse repetition rate) that produces near-infrared light (NIR) capable of stimulating photochemical reactions as a result of its extremely short pulse width (approximately 200 fs). Two near-infrared photons arrive simultaneously where the laser has been focused, allowing photochemical reactions to occur which normally require ultraviolet light. Therefore, development of new PDT agents for use with NIR light is not required to achieve the benefits of NIR activation. The applicants have recently shown that two-photon induced photochemistry can be used to kill bacteria and breast cancer cells in vitro. In this Phase I study, they propose to determine the two-photon light dose and time required to produce photodynamic therapy in vivo using laboratory mice treated with psoralen or Photofrin. The commercial applications are numerous. The improved PDT system offers new therapies for cancer without the debilitating side effects associated with surgery, ionizing radiation or chemotherapy. This system offers improved safety when compared to single-photon medical laser applications including non-photodynamic laser therapies for dermabrasion, retinal repair, tissue ablation and removal of arterial blockage.
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