PORPHYRAZINE TUMOR CONTRAST AGENTS

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Reliable, non-invasive methods of tumor detection are of vital importance. Shortcomings in current imaging modalities make it imperative to devise new, reliable, non-invasive imaging methods, along with corresponding imaging agents that can be administered frequently for screening, and for tumor monitoring during and after therapy. Optical absorbance and fluorescence imaging of soft tissue is possible with near-it light at wavelengths beyond the absorbance of hemoglobin, lambda equal to or less than 700 nm. We show in this proposal that a relatively unknown class of porphyrin variants, the porphyrazines (pzs) represent a uniquely attractive combination of optical, chemical, and biological properties for use as contrast agents in optical absorbance and fluorescence imaging of tumors. Preliminary results have already revealed that pzs are nontoxic and are taken up by tumor cells. We propose to optimize the pzs as intravenous-delivered, tumor-specific optical contrast agents, through use of synthetic strategies we have developed and cell screening methods we have perfected. SPECIFIC AIM 1. Chemically synthesize classes of pzs that are simultaneously optimized for tumor uptake, and for the near infra-red optical absorption and fluorescence characteristics required for optical imaging. SPECIFIC AIM 2. Document the non-toxic nature of these new pzs and to measure the kinetics of uptake, retention, and release of the pzs in normal and tumor cell lines. SPECIFIC AIM 3. Use the results of the biological tests in an iterative way to refine the chemical syntheses. GOAL: To correlate structural modifications of near-it absorbing/emitting pzs with their biological activity, so as to develop optimized, iv-deliverable optical contrast agents.