Fluorescence Image-Guided Near Infrared (NIR) Photodynamic Therapy (PDT) Agent

DESCRIPTION provided by applicant Photolitecandapos s patented technology is focused on developing improved agents for tumor imaging image guided surgery and or photodynamic therapy PDT The proposed STTR proposal includes fluorescence image guided PDT a andquot See and Treatandquot approach The fluorescence imaging compound with long wavelength absorption near nm should be extremely useful for image guided therapy PDT alone or surgery PDT for treating a variety of tumors especially large and deeply seated tumors Due to its non radioactive nature the fluorescence tomography currently being explored for human use will have a significant impact in tumor diagnosis In summary such compounds can be used for tumor detection monitoring the tumor response assessing disease and image guided therapy The NIR photosensitizer PS technology developed at Roswell Park Cancer Institute RPCI is transferred to Photolite LLC a spin off company of RPCI is highly effective exhibit a large Stokes shift and does not show any significant toxicity Therefore the success rate for further development is high Due to the presence of a chiral center at position the bacteriochlorin based PS nm it exists as a mixture of R andamp S isomers in a ratio The in vitro in vivo PDT efficacy of both the isomers was similar to the parent PS isomeric mixture without any significant skin phototoxicity a major drawback associated with most of the porphyrin based PS e g Photofrin and m THPC Foscan However a detailed Pharmacokinetics PK Pharmacodynamics PD of the PS as an isomeric mixture or as a pure R and S isomers has not been investigated On the basis of limited preliminary results it is not yet clear whether to pursue the development of the isomeric mixture or the individual isomers Therefore the Phase I II study has been divided in two parts Phase I a To use the treatment parameters of NIR PS and its stereoisomers R andamp S already established in mice bearing Colon tumors to brain U Gl L and head andamp neck SCC tumors and investigate its utility in fluorescence imaging and PDT b To investigate normal organ toxicity of the PS and its stereoisomers in mice and c Have a meeting with FDA select the PS and plan toxicological studies for Phase II studies accordingly Phase II a To use the GMP manufactured PS formulated in a GLP facility for PDT efficacy in the selected tumor model Phase I at variable light dosimeter b To investigate toxicity and PK PD studies of the PS in two animal species following the US FDA requirements and finally c Submit the application to FDA for Phase I human clinical trials PUBLIC HEALTH RELEVANCE The proposed fluorescence image guided photodynamic therapy with NIR photosensitizers near nm should help to image the tumor tumor margins with enhanced efficacy survival and improved quality of life to cancer patients The proposed fast track Phase I II STTR proposal is aimed to compare the PDT and toxicological efficacy of the stereo isomers R and S with the parent molecule and select the best isomer for Phase I human clinical trials of either head andamp neck or brain cancer