I-Labeled Anti-HER2 Nanobody for Targeted Radionuclide Therapy of HER2-Positive Breast Cancer.

Purpose: The unique structure of nanobodies is advantageous for the development of radiopharmaceuticals for nuclear medicine. Nanobodies targeted to human epidermal growth factor receptor 2 (HER2) can be used as tools for the imaging and therapy of HER2-overexpressing tumors. In this study, we aimed to describe the generation of a I-labeled anti-HER2 nanobody as a targeted radionuclide therapy (TRNT) agent for HER2-positive breast cancer.

Methods: The anti-HER2 nanobody NM-02 was labeled with I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group.

Results: I-NM-02 could be readily prepared with satisfactory radiochemical purity and stability in vitro. Apparent tumor uptake was observed in HER2-positive tumor-bearing mice with rapid blood clearance and favorable biodistribution. I-NM-02 could significantly inhibit tumor growth and extend the life of these mice with good organ compatibility. Negligible tumor accumulation and inhibitory effects of I-NM-02 were observed in the negative control group.

Conclusion: I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.