Complete removal of
tumors by surgery is the most important prognostic factor for
cancer patients with the early stage
cancers. The ability to identify invasive
tumor edges of the primary
tumor, locally invaded small
tumor lesions, and drug resistant
residual tumors following
neoadjuvant therapy during surgery should significantly reduce the incidence of local
tumor recurrence and improve survival of
cancer patients. In this study, we report that
urokinase plasminogen activator (uPA) and its
receptor (uPAR) are the
ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the
tumor border. Recombinant
peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR)
dye molecules either as
peptide-imaging or
peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic
tumor xenografts or mouse mammary
tumors led to the accumulation of the probes in the
tumor and stromal cells, resulting in strong signals for optical imaging of
tumors and identification of
tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the
tumor edge or active
tumor stroma immediately adjacent to the
tumor cells. Furthermore, following targeted
therapy using uPAR-targeted
theranostic nanoparticles,
residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-
dye-labeled
theranostic nanoparticles in drug resistant
tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and
theranostic agents for
image-guided surgery.