Detection of colorectal cancer using a small molecular fluorescent probe targeted against c-Met

Colorectal cancer (CRC), a highly heterogeneous genetic disease, is currently the second leading cause of cancer-related deaths worldwide. This malignant cancer is typically preceded by the development of precancerous lesions, which are challenging to distinguish their subtle morphologic changes. Molecular-based fluorescence imaging can effectively identify lesion targets to enhance image contrast and improve the detection of early neoplasia comparing to conventional wide-light screening endoscopy. C-Met has been identified as overexpressed in CRC advanced stage and has been suggested as a validated potential theranostic target. Herein, we developed a new small molecular fluorescence probe, namely Crizotinib-PEG(4)-MPA, specifically binds to c-Met in CRC cells and colitis-associated cancer adenoma. In vitro binding studies confirmed the specificity and selectively of Crizotinib-PEG(4)-MPA against c-Met, the corresponding apparent equilibrium dissociation constants (K-d) was 3.86 mu M for Crizotinib-PEG(4)-MPA. Additionally, the probe was carried out to c-Met positive tumor-bearing mice in vivo to explore the diagnostic potential clinical value, the method used a randomized block design to cluster mice into groups and found the tumor/normal signal ratio value up to 4.23 (95% confidence interval (CI) 4.07-4.39) at 6 h. More importantly, Crizotinib-PEG(4)-MPA was used to detect the occurrence of the colon adenoma and the in vivo imaging results showed the mean fluorescence intensity of the CAC colon is significantly higher than that in the normal group (P < 0.001). Furthermore, the immunofluorescence signals of biopsies samples demonstrated the probe indeed targets the c-Met and possesses the property to distinguish colon adenoma from normal colon tissue. Altogether, this novel fluorescence probe, with excellent C-met-targeting ability, has a substantial potential to serve as a widely available in vivo tracer for the early diagnosis and monitoring of colorectal cancer.

Automated summary

Colorectal cancer (CRC) is a highly heterogeneous genetic disease and early diagnosis is crucial. Molecular-based fluorescence imaging can effectively enhance cancer detection, and the new Crizotinib-PEG(4)-MPA fluorescence probe has the potential to diagnose colorectal cancer and distinguish colon adenomas.