Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy in patients with cancer. HER2 expression in a complex environment, such as in a heterogeneous tumor, makes the precise assessment of the HER2 status difficult using current methods. In this study, we developed a novel ^99mTc-labeled anti-HER2 single-domain antibody (^99mTc-NM-02) as a molecular imaging tracer for the noninvasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in 10 patients with breast cancer. Our data showed that no drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid; however, only background tracer levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10^–3 mSv/MBq, and tracer uptake was visually observed in the primary tumors and metastases. A maximal standard uptake value of 1.5 was determined as a reasonable cutoff for identifying HER2 positivity using SPECT/CT imaging. Our ^99mTc-NM-02 tracer is safe for use in breast cancer imaging, with reasonable radiation doses, favorable biodistribution, and imaging characteristics. ^99mTc-NM-02 SPECT imaging may be an accurate and noninvasive method to detect the HER2 status in patients with breast cancer.

中文翻译：

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开发用于 SPECT/CT 评估乳腺癌 HER2 表达的 99mTc 标记单域抗体

准确测定人表皮生长因子受体 2 (HER2) 的表达对于癌症患者的 HER2 靶向治疗至关重要。HER2 在复杂环境（例如异质性肿瘤）中的表达使得使用当前方法难以精确评估 HER2 状态。在这项研究中，我们开发了一种新型^99m Tc 标记的抗 HER2 单域抗体（^99mTc-NM-02) 作为无创检测 HER2 表达的分子成像示踪剂，并在 10 名乳腺癌患者中研究了其安全性、辐射剂量学、生物分布和肿瘤靶向潜力。我们的数据显示没有发生药物相关的不良反应。示踪剂主要蓄积于肾脏和肝脏，少量被脾脏、肠和甲状腺吸收；然而，在通常发生原发性肿瘤和转移的其他器官中仅观察到背景示踪剂水平。平均有效剂量为 6.56 × 10 ^–3 mSv/MBq，在原发肿瘤和转移瘤中肉眼观察到示踪剂摄取。最大标准摄取值 1.5 被确定为使用 SPECT/CT 成像识别 HER2 阳性的合理截止值。我们的^99mTc-NM-02示踪剂具有合理的辐射剂量、良好的生物分布和成像特性，可安全用于乳腺癌成像。^99m Tc-NM-02 SPECT 成像可能是检测乳腺癌患者 HER2 状态的一种准确且无创的方法。