Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model.

Background: Cancer stem cells (CSCs) are involved in drug resistance, metastasis, and relapse of cancers, which can significantly affect tumor therapy. Hence, to develop specifically therapeutic target probe at CSCs for improvement of survival and quality of life of cancer patients is urgently needed. The CD166 protein has been suggested to be involved in colorectal cancer (CRC) tumorigenesis and to be considered a marker for colorectal CSCs (CRCSCs) detection. In this study, therefore, we attend to apply a nuclear imaging agent probe, Glycine-Cystine-linked CD166-targeted peptides (CD166tp-GC), to detect the changes of CD166 level in a CRC xenograft mouse model.

Results: We isolated the CD166-positive cells from the HCT15 CRC cell line (CD166HCT15) and evaluated their morphology and ability of clone formation, migration, protein expression, and drug resistance. The CD166-positive HCT15 cells display the CSCs characteristics. We discovered and designed a CD166-targeted peptide (CD166tp-GC) as a targeted probe of CRC stem-like cell for cell binding assay. The CD166tp-GC confirmed the CD166 protein targeting ability in CD166HCT15 cells. The diethylenetriaminopentaacetic acid (DTPA)-conjugated CD166tp-GC further was labeled with indium-111 (In-DTPA-CD166tp-GC) as nuclear imaging agent for imaging and bio-distribution analysis in vivo. Finally, we observed that the In-DTPA-CD166tp-GC was significantly enhanced in tumor tissues of CD166HCT15 xenograft mice as compared to the non-CD166tp-GC control.

Conclusions: Our results indicated that the indium-111-labeled CD166tp-GC may be served as a powerful tool for colorectal CSCs nuclear imaging in the CRC patients.