What question did this study set out to answer?

The aim is to explore CDH3 as a target for theranostic strategies in triple-negative breast cancer.

January 25, 2026

Preclinical Study of CDH3-Targeted 89Zr/177Lu Theranostics in Triple-Negative Breast Cancer.

Key Points

The aim is to explore CDH3 as a target for theranostic strategies in triple-negative breast cancer.
Analyzed CDH3 expression using flow cytometry.
Established a HCC1806 mouse xenograft model with CDH3 overexpression.
Evaluated dual-functional probe 89Zr/177Lu-11E10C11 through various assays including biodistribution and imaging.
Labeled anti-CDH3 monoclonal antibody with 89Zr or 177Lu for separate assessment of diagnostics and therapy.
CDH3 was highly expressed in TNBC (HCC1806).
89Zr-labeled probe clearly outlined tumor lesions with a maximum standardized uptake value of 2.11 ± 0.31.
177Lu treatment resulted in significant tumor growth inhibition (TGI of 74.94%).
Therapeutic application showed no hematologic toxicity or damage to normal organs.

Abstract

Triple-negative breast cancer (TNBC) is characterized by poor prognosis, limited therapeutic options, and low survival rates, underscoring the urgent need for novel and effective treatment strategies. This study aimed to investigate the potential of CDH3 as a theranostic target for TNBC and to develop a CDH3-based targeted radionuclide theranostic approach. Flow cytometry was used to analyze CDH3 expression, and a CDH3-overexpressing HCC1806 xenograft mouse model was established. The performance of the dual-functional probe 89Zr/177Lu-11E10C11 was systematically evaluated through radioligand binding, internalization, PET/CT imaging, and biodistribution assays. The anti-CDH3 monoclonal antibody 11E10C11 was labeled with either 89Zr or 177Lu to separately assess diagnostic capability and targeted antitumor efficacy. Results demonstrated that CDH3 was highly and specifically expressed in TNBC (HCC1806), with 89ZrZr-DFO-11E10C11 clearly delineating tumor lesions (72 h SUVmax, 2.11 ± 0.31) and 177LuLu-DOTA-11E10C11 significantly inhibiting tumor growth (TGI, 74.94%) without inducing hematologic toxicity or damage to normal organs, indicating favorable safety. In conclusion, CDH3 is a promising theranostic target for TNBC, and the 89Zr/177Lu-11E10C11 dual-functional probe successfully achieved an integrated "diagnosis-therapy" strategy, offering a novel approach with translational potential for precision management of TNBC.

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