Multi-modal imaging probe for EpCAM overexpressed in breast cancer.

Breast cancer is a highly lethal and aggressive form of cancer. Early-stager diagnosis and intraoperative guidance are important endeavors for reducing associated morbidity and mortality among breast cancer patients. Epithelial cell adhesion molecule (EpCAM) is aberrantly expressed in the majority of breast carcinoma, making it an attractive imaging biomarker. Herein, we have designed novel EpCAM-targeting peptides (denoted as YQ-S) for precise breast carcinoma detection. The greater binding affinity of the designed peptide YQ-S2 over YQ-S1 and the reported peptide SNF was displayed on different cell lines with flow cytometry analysis, showing a positive correlation with the expression of EpCAM. Besides, YQ-S2 displayed an ideal biosafety profile with no evidence of any acute toxicity. Thus, YQ-S2 was chosen to represent YQ-S. By linking with the near-infrared fluorescent dye (MPA), we further developed the EpCAM-targeting probe (YQ-S2-MPA) for real-time imaging and fluorescence-guided resection of breast cancer tumors. In vivo imaging of the MCF-7 tumor-bearing model demonstrated higher tumor uptake of YQ-S2-MPA compared with that of SNF-MPA. The maximum tumor-to-normal tissue signal ratio of YQ-S2-MPA was 5.1, which was about 2 times that of SNF-MPA. Meanwhile, the metastatic lesions in 4T1 lung metastasis, and lymph node metastasis (LNM) mice were successfully detected under this imaging system. Notably, YQ-S2-MPA had excellent performance in surgical navigation studies in the preclinical models. Moreover, we exploited the 99mTc-HYNIC-YQ-S2 to localize EpCAM positive tumors successfully. These data proved that YQ-S2 can distinguish EpCAM-positive orthotopic and metastatic tumors from surrounding normal tissues accurately, and possesses the clinical potential as a surgical navigation probe.

A novel peptide targeting c-Met for hepatocellular carcinoma diagnosis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with limited diagnosis. Mesenchymal epithelial transition factor (c-Met) has become a hot target for cancer diagnosis and therapy, which is overexpressed in HCC. In this study, we labeled a novel c-Met targeting peptide YQ-M3 with a near-infrared fluorescent dye MPA and a radionuclide technetium-99m for HCC detection. YQ-M3-MPA showed high affinity for c-Met positive HepG2 tumor in vitro and higher tumor uptake and higher T/N ratio than GE137-MPA (a positive tracer for c-Met) in HepG2 tumor-bearing mice in vivo by fluorescence imaging. In addition, 99mTc-HYNIC-YQ-M3 also showed significant tumor uptake in vivo through SPECT imaging. These results indicated that c-Met positive tumors were successfully detected via fluorescence and SPECT imaging using YQ-M3-MPA and 99mTc-HYNIC-YQ-M3, respectively, and further suggested that YQ-M3-MPA and 99mTc-HYNIC-YQ-M3 have some possibly potential clinical applications for HCC diagnosis.