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Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer
Siao-Syun Guan1, Cheng-Tien Wu2,3, Tse-Zung Liao1
1Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.
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, Glycine18-Cystine-linked CD166-targeted peptides (CD166tp-G18C), 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 (CD166+HCT15) 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-G18C) as a targeted probe of CRC stem-like cell for cell binding assay. The CD166tp-G18C confirmed the CD166 protein targeting ability in CD166+HCT15 cells. The diethylenetriaminopentaacetic acid (DTPA)-conjugated CD166tp-G18C further was labeled with indium-111 (111In-DTPA-CD166tp-G18C) as nuclear imaging agent for imaging and bio-distribution analysis in vivo. Finally, we observed that the 111In-DTPA-CD166tp-G18C was significantly enhanced in tumor tissues of CD166+HCT15 xenograft mice as compared to the non-CD166tp-G18C control.
Conclusions:
Our results indicated that the indium-111-labeled CD166tp-G18C may be served as a powerful tool for colorectal CSCs nuclear imaging in the CRC patients.
Insights
This study developed a novel nuclear imaging probe, indium-111-labeled CD166-targeted peptides (111In-DTPA-CD166tp-G18C), to detect colorectal cancer stem cells (CSCs). The probe effectively targeted CD166-positive cells, showing potential for improved colorectal cancer diagnostics.
Area of Science:
- Oncology
- Nuclear Medicine
- Biotechnology
Background:
- Cancer stem cells (CSCs) drive tumor resistance, metastasis, and relapse, necessitating targeted therapies.
- CD166 protein is implicated in colorectal cancer (CRC) tumorigenesis and serves as a marker for colorectal CSCs (CRCSCs).
- Developing targeted probes for CRCSCs is crucial for improving patient survival and quality of life.
Purpose of the Study:
- To develop and evaluate a novel nuclear imaging agent for detecting colorectal CSCs.
- To target the CD166 protein, a marker for CRCSCs, using a specifically designed peptide probe.
- To assess the probe's efficacy in a colorectal cancer xenograft mouse model.
Main Methods:
- Isolated CD166-positive HCT15 CRC cells and confirmed their CSC characteristics.
- Designed and synthesized a CD166-targeted peptide probe (CD166tp-G18C).
- Conjugated the probe with DTPA and radiolabeled it with indium-111 (111In-DTPA-CD166tp-G18C) for nuclear imaging.
Main Results:
- CD166-positive HCT15 cells exhibited CSC properties including clone formation, migration, and drug resistance.
- The CD166tp-G18C probe demonstrated specific binding to CD166-positive cells.
- In vivo imaging revealed significantly enhanced accumulation of 111In-DTPA-CD166tp-G18C in tumor tissues of xenograft mice compared to controls.
Conclusions:
- The developed 111In-DTPA-CD166tp-G18C probe shows high specificity for CD166-positive colorectal CSCs.
- This radiolabeled peptide holds promise as a powerful tool for nuclear imaging of CRCSCs in patients.
- The findings support the potential for improved diagnostic capabilities in colorectal cancer management.
