We demonstrate PDT effects at >2 cm penetration depth through the bodies of SCID mice hosting human small cell and non-small cell lung tumors. A novel porphyrin-based NIR sensitizer, that is activated with high peak intensity 800 nm laser light in the NIR tissue transparency window, was used in these studies. The PDT sensitizer carries an octreoate targeting peptide useful for many human lung cancers that overexpress the SST2 receptor. Currently, only small lung tumors are ever treated with this modality due to poor tissue penetration of activating light in the visible wavelengths. Given the acute need for therapies (such as PDT) that would be effective in drug resistant lung cancer, we initiated work to evaluate the potential of our NIR activated PDT sensitizers in human lung tumor xenografts. Laser activation was conducted through the body of the host mouse to assess the ability of our protocols to kill tumor tissue at a modest depth without damaging normal tissues. Significant tumor regressions (including complete regression) were seen in 6/6 NCI-H69 SCLC tumor bearing mice, while regressions were seen in 3/6 A-549 non-SCLC tumor bearing mice. Heating was minimal in the tumor during laser irradiation. Neutrophil infiltration of the tumor was extensive for regressing tumors but, while immature neutrophils and other granulocytes were present in areas surrounding the tumor, these cells failed to infiltrate the neoplasm in tumors that did not regress. Using in vivo imaging with FITC conjugated high molecular weight dextran, we also demonstrate that our PDT protocol leads to vascular shutdown in the tumor within 6 hours of treatment, and, from microarray expression profiling, we are able to show increases of several transcripts known to be elevated in post-PDT tumor responses. These results are encouraging, particularly for SCLC. Studies with larger animals will clarify the maximal achievable tissue penetration depth, which currently is limited due to small thickness of mouse body. Supported by the Montana MBRCT program and the MSU Center for Bio-inspired Nanomaterials.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA