99M Tc-Peptides for Detection of Breast Cancer

摘要

The goal of this project was to identify peptides from phage display peptide libraries which bind with high affinity to the mutant EGFRvIII receptor present in breast tumors. The peptides selected were radiolabeled with technetium-99m (99mTc) and tested for their potential as agents in the detection of breast cancer. Using available phage display peptide libraries, we have identified five consensus peptides that show affinity for cells expressing the mutant EGFRvIII receptor. Characterization of these selected peptides was by ELISA and radiolabeled cell binding studies. First, the labeled phage were tested in in vitro assays and in mice with tumors. Specific binding of The labeled phage to the study cells was found relative to the control cells. Also, mice with tumors expressing the mutant receptor showed enhanced accumulation of the labeled phage over mice with tumors expressing the wild-type receptor. The consensus peptides were identified through analysis of the phage DNA. The peptides were synthesized, then conjugated to a chelator for radiolabeling with 99mTc. All peptides have been tested in in vitro assays and tested in tumor bearing mice. The in vivo studies show that the 99mTc peptide clear the circulation quickly and demonstrate accumulation in breast tumor. Peptides have also been evaluated against a panel of tumor from clinical pathology. Early results suggest a distinction of peptides for various tumors.