Synthesis, characterization and two-photon PDT efficacy studies of triads incorporating tumor targeting and imaging components

Over the past three years we have described the rationale for using new photosensitizers (PS) with greatly enhanced multi-photon absorption. In particular, we have synthesized new porphyrin-based photosensitizers that also incorporate small molecule targeting agents that direct the ensemble to over-expressed tumor receptor sites, as well as Near-infrared imaging agents that will allow practical image-guided two-photon PDT in the tissue transparency window (750-1000 nm) at laser fluences that are harmless to surrounding healthy tissue. We have previously shown (PW2006) successful treatment of human breast cancer models (MDA-MB-231) in SCID mice, and have recently extended these studies to the treatment of both human small cell (SC) (NCI-H69) and non-small cell (NSC) (A-459) models in SCID mice. We have demonstrated that lung cancer xenografts can be successfully treated by irradiating from the side of the mouse opposite the implanted tumor, thereby passing through ca. 2 cm of mouse skin, tissue and organs before encountering the bulk tumor. These results suggest that this technology can be used to treat deep subcutaneous spontaneous tumors in larger animal models (e.g. canine). We would also emphasize that the synthetic route to these triads attaches the targeting moiety in the last step of the synthesis, and can be easily changed, thus allowing a myriad of targeting agents to be employed, opening the door to the possibility of patient-specific PDT.