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 131 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 131 I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of 131 I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of 131 I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group. Results 131 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. 131 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 131 I-NM-02 were observed in the negative control group. Conclusion 131 I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with a high mortality rate. One of the main reasons for this poor prognosis is the failure of a specific diagnosis. As a tumor-homing and penetrating peptide, iRGD has not only the properties of binding to neuropilin-1 and integrin αvβ3 but also internalizing into TNBC cells. In this study, we designed and prepared 99mTc-labeled iRGD (99mTc-HYNIC-iRGD) as a single-positron emission computed tomography (SPECT) imaging probe and investigated its feasibility for the targeted diagnosis of TNBC. The results showed that the iRGD peptide had acceptable biocompatibility within the studied concentration range and could specifically bind to TNBC cells in vitro. The 99mTc-HYNIC-iRGD was readily prepared with high radiochemical purity and stability. SPECT imaging of 99mTc-HYNIC-iRGD in a TNBC tumor-bearing mouse model showed obvious tumor accumulation with rapid blood clearance and favorable biodistribution. Our findings indicate that this active-targeted strategy has great potential to be developed as a novel tool for TNBC imaging.

We report a new 131I-labeling functional platform for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of breast adenocarcinoma. In this study, polyethyleneimine (PEI) based nanogels (P.NH2 NGs) were prepared by water/oil polymerization, modified with targeted agent phenylboronic acid (PBA), and labeled with radionuclide 131I. The NGs without 131I-labeling own a spherical structure, uniform size distribution, and good cell viability. After 131I-labeling, the obtained 131I-PBA-PHP NGs displayed much higher cellular uptake than the non-targeted NGs due to the good softness and fluidity of NGs and the PBA targeting. The in vivo results demonstrated that 131I-PBA-PHP NGs could specifically target breast cancer cells and efficiently aggregate into xenograft breast adenocarcinoma for tumor SPECT imaging and specific radiotherapy. The developed 131I-labeling NGs may be used as a promising platform for efficient radioactive theranostic nanoplatform of tumor.

Novel strategies for diagnosing triple-negative breast cancer (TNBC) are essential for effective clinical treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) are potential targets for tumor imaging...