Development of novel breast cancer-targeted spect imaging peptides by phage display
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Malignancy of the breast is the leading cause of cancer among women and the second leading cause of cancer-related death. Despite implementation of mammograms and breast exams, there still exists a need to detect highly aggressive cancer at its earliest stage. Development of targeted molecules, such as peptides, by phage display allows for specific imaging of a targeted antigen. The hypothesis of this dissertation was that phage display could be used select novel peptides for breast cancer imaging. In vivo phage display selection is a strategy that allows for selection of peptides based on their function in the environment in which they will be used. The work here demonstrated that in vivo phage display successfully was able to select a peptide with improved pharmacokinetics and tumor targeting in comparison to a previous generation. Additionally, the selection yielded a peptide that mimicked a putative tumor vasculature. associated protein termed EGFL6. EGFL6 was determined to be expressed in breast cancer and may serve as the basis for future investigations. Finally, a peptide was discovered that bound to and imaged BT-474 human breast cancer tumors in mice. This cell line is of importance because it represents resistance susceptible breast cancer, a major cause of death among women. These results demonstrate the utility of phage display and highlight the novel targeting agents that can be obtained by the technology.