Photodynamic therapy (PDT) is a new modality for the treatment of diseases which involve the rapid proliferation of cells, e.g. cancer, psoriasis ad neovasclarization. Further, understanding of those factors that influence the structure/activity relationships in photodynamic therapy will lead to the rational design of new and more efficacious compounds for PDT. The proposed study is designed to rapidly obtain information on known mechanisms and effects of PDT exhibited by those benzochlorins (BC's) which showed promising photophysical and preliminary photobiological properties in the Phase I study. Based on these results, we propose to synthesize and study a number of similar but new functionalized BC's with an eye toward further understanding structure-activity relationships in disease model systems. In vitro evaluation of selected potent BC's will take place using a novel differentiation model. A number of in vivo models specifically designed to examine different targets of photodynamic action will be used. In vivo studies will focus on BC-induced phototoxicity, optimal drug dose and light treatment parameters for each photosensitizer, pharmacokinetics, and potential treatment of cancer and corneal neovascularization. This Phase II study will provide valuable information on structure- activity relationships in the BC series. The phase II results will provide identification of compounds worthy of further animal study and potential clinical use for specific application in phase III of the proposal.
Photodynamic Therapy has the potential to impact many clinical disciplines, and the market for this technology is significant. Proliferative disease, such as cancer, psoriasis and restenosis together affect millions of people in the U.S. every year. Cost effective and less toxic treatment of these diseases, as well as vascular and neovascular disease, is needed.
