131I-Labeled Anti-HER2 Nanobody for Targeted Radionuclide Therapy of HER2-Positive Breast Cancer

Abstract

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.

Micronutrient Status and Breast Cancer: A Narrative Review

“…Very similar results had been observed in some previous studies [288]. Moreover, the literature supports that iodine can also be used in photoimmunotherapy [289] and brachytherapy [290,291] and has potential in targeted radionuclide therapy [292]. A very interesting application of iodine is in 125I seeds, which can be implanted into a patient's lesion to provide treatment, improve the treatment's effects, reduce adverse reactions, and better the quality of life.…”

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

“…With a single dose of 3.0 MBq, 211 At-VHH_1028 led to complete tumor regression in three of four mice bearing BT474 breast cancer cell xenografts [150]. The same antitumor effect was also observed when 131 I-NM-02, another nanobody, was used in HER2-positive xenografts [151]. 177 Lu-ABY-027 affibody was also evaluated for its ability to treat HER2-positive tumors and showed higher efficacy when combined with trastuzumab in comparison to monotherapies [152].…”

Reviving a Classic Antigen with a Cutting-Edge Approach: Nanobodies for HER2+ Breast Cancer

“…After successfully developing the 99m Tc-NM-02 MI tracer with NM-02 NB as the lead compound [ 59 ], Zhao et al recently investigated whether labeling said NB with 131 I may be employed as a targeted radionuclide treatment agent for HER2+ breast cancer in xenografted mice [ 88 ]. One of the main reasons 131 I was employed in this work is because its theranostic properties, namely the ability to emit β-particles and γ rays, enable it to perform both SPECT imaging and radionuclide therapy [ 89 ].…”

“…One of the main reasons 131 I was employed in this work is because its theranostic properties, namely the ability to emit β-particles and γ rays, enable it to perform both SPECT imaging and radionuclide therapy [ 89 ]. In comparison to mice with HER2- tumors, 131 I-NM-02-treated HER2+ xenografts displayed significantly reduced tumor growth and increased survival times with optimal organ compatibility, hinting at the potential translation of said agent for clinical use [ 88 ].…”