Preclinical evaluation shows that 5T4-targeted therapy inhibits tumor growth in colorectal cancer, suggesting a new treatment option.
The oncofetal antigen 5T4 is highly expressed in colorectal cancer (CRC), making it a promising theranostic target. In this study, we developed the diagnostic tracer [⁸⁹Zr]Zr-DFO-HB5 (5T4 monoclonal antibody) and therapeutic agents [¹⁷⁷Lu]Lu/[¹⁶¹Tb]Tb-DOTA-HB5, establishing a novel theranostic strategy for CRC. We selected two 5T4-positive colorectal cancer cell lines and established subcutaneous xenograft models. Immuno-PET imaging revealed specific tumor targeting of [⁸⁹Zr]Zr-DFO-HB5 in 5T4-positive CRC mouse models. Ex vivo biodistribution studies showed high and sustained tumor uptake of [¹⁷⁷Lu]Lu/[¹⁶¹Tb]Tb-DOTA-HB5, with gradually decreasing radioactivity accumulation in normal organs over time. Targeted radionuclide therapy (TRT) further confirmed that [¹⁷⁷Lu]Lu/[¹⁶¹ Tb]Tb-DOTA-HB5 significantly inhibited tumor growth in both models. Biosafety evaluation revealed only mild hematological toxicity, without obvious short-term organ damage. In conclusion, [⁸⁹Zr]Zr-DFO-HB5 enables noninvasive detection of 5T4 expression, while [¹⁷⁷Lu]Lu/[¹⁶¹Tb]Tb-DOTA-HB5 exhibits potent antitumor efficacy and favorable biosafety. The study provides a potential theranostic platform for 5T4-positive CRC and related malignancies.
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Liang et al. (2026) studied this question.
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