Chemically Modified Bacteriophage as a Streamlined Approach to Noninvasive Breast Cancer Imaging

By using efficient synthetic protocols to conjugate small molecules to phage coat proteins, we can directly convert cell surface marker specific phage isolated from library screens into imaging agents that can target and differentiate breast cancer tissues. In the current work, I have utilized phage evolved to target HER3, CD44, and CD73 cell surface proteins, in addition to those previously described that bind EGFR and HER2. The abilities of the modified phage to bind their targeted cell surface receptors following chemical manipulations were evaluated in vitro by using flow cytometry and confocal microscopy assays, and it was found that the synthetic modifications performed did not significantly alter phage binding ability. Experiments in vivo with mouse xenograft models were used to determine biodistribution and tumor targeting abilities of the agents in a physiological setting. Follow-up experiments using radio-tracers for thorough evaluation of bio-distribution and stability are currently in progress. Phage were also explored as agents for immunofluorescence staining of breast cancer tissues as a surrogate for tumor binding.