MEDI 53 |
| Early diagnosis of cancer may lead to a better prognosis, which could cure or prolong the lives of many cancer patients. Among various treatment modalities, photodynamic therapy (PDT) is a non-invasive technique for treating various forms of cancer. Success and limitations associated with Photofrin® triggered development of second generation photosensitizing agents worldwide. Among these compounds, HPPH (a pheophorbide-a analog, derived from chlorophyll-a) was found to be extremely effective with limited toxicity and is currently under Phase II clinical trials at our institute for various indications. Substitution of O-hexyl side chain in 3-(1'-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH) by O-iodobenzyl led to the development of methyl-3-(1'-m-iodobenzyloxyethyl) pyropheophorbide-a (S.K. Pandey et al, JMC, 2005, 48, 6286), which was found to be an effective PS in C3H mice implanted with RIF tumors. Further, the corresponding I-124 derivative could be used for PET imaging. We have now extended our approach in developing integrin-target “multi-functional agents” for the imaging and treating brain tumors. In order to achieve our goal the methyl-3-(1'-m-iodobenzyloxyethyl)pyropheophorbide-a and HPPH were separately linked with a cyclo(RGDfK)peptide known for its binding specificity to (alphavbeta3) integrin, a protein with high expression in brain tumors. The initial biological results are quite promising. The synthesis and biological efficacy of these conjugates will be presented.
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General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Division of Medicinal Chemistry |
