(131)I-Labeled Anti-HER2 Nanobody for Targeted Radionuclide Therapy of HER2-Positive Breast Cancer.
(131)I-Labeled Anti-HER2 Nanobody for Targeted Radionuclide Therapy of HER2-Positive Breast Cancer.
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DOI：
10.2147/ijn.s399322
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发表时间：
2023
影响因子：
8
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中科院分区：
文献类型：
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纳米抗体的独特结构有利于核医学放射性药物的开发。靶向人表皮生长因子受体2（HER 2）的纳米抗体可用作HER 2过表达肿瘤的成像和治疗工具。在这项研究中，我们的目的是描述131 I标记的抗HER 2纳米抗体作为HER 2阳性乳腺癌的靶向放射性核素治疗（TRNT）剂的产生。采用Iodogen法对抗HER 2纳米抗体NM-02进行131 I标记，并对其放化纯度和体外稳定性进行评价。研究了131 I-NM-02在正常小鼠体内的药代动力学特征。在HER 2阳性SKBR 3异种移植物中评价了131 I-NM-02的肿瘤蓄积、生物分布和治疗潜力;将HER 2阴性MB-MDA-231异种移植物用作对照组。~（131）I-NM-02的制备方法简便，放化纯度和体外稳定性良好。在HER 2阳性荷瘤小鼠中观察到明显的肿瘤摄取，具有快速血液清除和良好的生物分布。131 I-NM-02能显著抑制肿瘤生长，延长小鼠生命，并具有良好的器官相容性。在阴性对照组中观察到可忽略的肿瘤蓄积和131 I-NM-02的抑制作用。131 I-NM-02有可能作为HER 2阳性乳腺癌TRNT的新工具进行探索。
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 131I-labeled anti-HER2 nanobody as a targeted radionuclide therapy (TRNT) agent for HER2-positive breast cancer. The anti-HER2 nanobody NM-02 was labeled with 131I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of 131I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of 131I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group. 131I-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. 131I-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 131I-NM-02 were observed in the negative control group. 131I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.