The goal of this investigation is to develop a 99mTc-peptide agent for the diagnosis of ovarian cancer through scintigraphic imaging. To meet this objective peptides will be selected from phage display peptide libraries that show high specificity and affinity for the TAG-72 tumor associated glycoprotein present in about 95% of ovarian cancers. The TAG-72 glycoprotein represents an ideal target as a tumor imaging agent and may be useful for therapeutic applications as well. Phage display peptide libraries are a combinatorial methodology that offer great potential for identification of cancer specific agents. The goals of this study will be met with the following project plan: 1). Using phage display screening techniques, peptides that bind with high specificity and high affinity (KD) to the tumor associated TAG-72 will be identified. 2). 12 selected phage-peptides will be radiolabeled with 99mTc using MAGS for initial testing. 6 lead peptides will be selected for synthesis and further testing. For labeling with 99mTc a Gly-Gly-Gly-Cys (N3S) will be added during peptide synthesis for evaluation in vitro and in mouse tumor models. The optimum peptide should show a low KD, stability in serum, low accumulation in normal tissues and specific tumor accumulation relative to normal tissues and a control tumor. Tumor to normal tissue ratios of greater than 5:1 are expected to be achieved. 4). To achieve improved affinity, constructs containing multiple peptides will be made through construction of multiple antigenic peptides (MAP) during peptide synthesis or polyethylene glycol (PEG) strategies to create polyvalent entities. 5). The high affinity binding 99mTc-multivalent peptide constructs will be characterized for binding to tumor cubes, and biodistribution and targeting potential in mouse tumor models. The agent developed in these studies could be of great benefit in the diagnosis of ovarian cancer, not only the primary site of disease, but possibly metastases as well. ? ? ?
| Chen, Ling; Wang, Yi; Cheng, Dengfeng et al. (2011) Comparing two TAG-72 binding peptides previously identified by phage display as potential imaging agents. Nucl Med Commun 32:920-4 |
| Xiao, Nan; Cheng, Dengfeng; Wang, Yi et al. (2011) Identification of a high affinity TAG-72 binding peptide by phage display selection. Cancer Biol Ther 11:22-31 |
| Chen, Ling; Wang, Yi; Liu, Xinrong et al. (2008) A new TAG-72 cancer marker peptide identified by phage display. Cancer Lett 272:122-32 |
| Rusckowski, Mary; Gupta, Suresh; Liu, Guozheng et al. (2007) Evidence of specificity of radiolabeled phage display peptides for the TAG-72 antigen. Cancer Biother Radiopharm 22:564-72 |
