Photodynamic therapy has been approved for certain indications in the USA, Japan, Canada, France and Netherlands. The only drug approved, Photofrin, is not ideal and a significant research effort has led to the development of second generation sensitizers. Many of these agents are hydrophobic and need formulation to be administered. This significantly increases the time and cost of drug preparation, in many cases by well over 100%. These factors are increasingly important in today's climate of cost containment in the health industry. This Phase I application addresses the problems associated with delivery of hydrophobic sensitizers by the preparation and biological evaluation of more water soluble photodynamic agents. Synthesis will concentrate on phthalocyanine chemistry with ease of synthesis, potential applicability to scale-up and minimalization of isomer formation as priorities. Given the 6 month time frame of this study, biological evaluation will consist of an assessment of in vivo tumor response in a rat chondrosarcoma model and a mechanistic study to delineate the contributions of direct versus indirect cell kill mechanisms to the photodynamic response. The goal of this study is the identification of candidate sensitizers for further evaluation, leading to the submission of an Investigational New Drug application to the FDA. PROPOSED COMMERCIAL APPLICATION: Photodynamic therapy has been approved for use as a treatment of cancer and is in clinical phase testing for indications in urology, ophthalmology and dermatology. Pre- clinical testing in additional areas such as immunology and cardiology have also been reported. The potential exists therefore for PDT to treat a wide variety of diseases.
Thesaurus Terms:chemical synthesis, drug design /synthesis /production, neoplasm /cancer photoradiation therapy, photosensitizing agent, phthalocyanin amphiphilicity, drug screening /evaluation, water solubility laboratory ratNational Cancer Institute (NCI)
