随着最近批准更有效的 HER2 靶向治疗，肿瘤人表皮生长因子受体 2 型 (HER2) 状态的测定变得越来越重要。临床体内 HER2 表达评估缺乏合适的方法。 Affibody 分子是小型亲和蛋白，非常适合受体的成像检测，其使用小型（分子量 6.5 kDa）非免疫球蛋白支架进行工程设计。用正电子发射器标记 Affibody 分子，能够开发出用于分子成像的敏感且特异的试剂。 SPECT 探针的开发将允许在无法进行 PET 的区域使用基于 Affibody 的成像。在这项首次人体研究中，我们评估了为 HER2 表达的 SPECT/CT 成像而开发的 99mTc-ZHER2:41071 Affibody 分子的安全性、生物分布和剂量测定。方法：招募了 31 名原发性乳腺癌患者，并将其分为三个队列（注射 500、1000 或 1500 µg ZHER2:41071），其中至少有 5 名具有高（阳性）HER2 肿瘤表达（IHC 评分为 3 或 2）的患者和 ISH 阳性）和 5 名 HER2 肿瘤表达低（IHC 评分 2 或 1 且 ISH 阴性）或缺失的患者。患者注射了 451 ± 71 MBq 99mTc-ZHER2:4107。注射后2、4、6和24小时后进行平面闪烁扫描，并在注射后2、4和6小时后进行SPECT/CT成像。结果：99mTc-ZHER2:41071 注射耐受性良好，且与不良事件无关。累积最高的正常器官是肾脏和肝脏。有效剂量为0.019±0.004 mSv/MBq。注射 1000 µg 可以在注射后 2 小时提供 HER2 阳性和 HER2 低或 HER2 阴性肿瘤之间的最佳标准区分（SUVmax 16.9 ± 7.6 与 3.6 ± 1.4，p < 0.005）。 HER2 阳性淋巴结转移中的 99mTc-ZHER2:41071 摄取 (SUVmax 6.9 ± 2.4, n = 5) 显着 (p < 0.05) 高于 HER2 低/阴性淋巴结 (SUVmax 3.5 ± 1.2, n = 5) 4). 99mTc-ZHER2:41071 使肝脏受累患者的肝转移可视化。结论：99mTc-ZHER2:41071 的注射显得安全并表现出良好的剂量测定。根据当前 HER2 靶向药物使用的定义，1000 µg 的蛋白质剂量可以最好地区分 HER2 阳性和 HER2 低/阴性表达的 HER2。© 作者。

The determination of tumor human epidermal growth factor receptor type 2 (HER2) status is of increasing importance with the recent approval of more efficacious HER2-targeted treatments. There is a lack of suitable methods for clinical in vivo HER2 expression assessment. Affibody molecules are small affinity proteins ideal for imaging detection of receptors, which are engineered using a small (molecular weight 6.5 kDa) nonimmunoglobulin scaffold. Labeling of Affibody molecules with positron emitters enabled the development of sensitive and specific agents for molecular imaging. The development of probes for SPECT would permit the use of Affibody-based imaging in regions where PET is not available. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the 99mTc-ZHER2:41071 Affibody molecule developed for SPECT/CT imaging of HER2 expression. Methods: Thirty-one patients with primary breast cancer were enrolled and divided into three cohorts (injected with 500, 1000, or 1500 µg ZHER2:41071) comprising at least five patients with high (positive) HER2 tumor expression (IHC score 3+ or 2+ and ISH positive) and five patients with low (IHC score 2+ or 1+ and ISH negative) or absent HER2 tumor expression. Patients were injected with 451 ± 71 MBq 99mTc-ZHER2:4107. Planar scintigraphy was performed after 2, 4, 6 and 24 h, and SPECT/CT imaging followed planar imaging 2, 4 and 6 h after injection. Results: Injections of 99mTc-ZHER2:41071 were well tolerated and not associated with adverse events. Normal organs with the highest accumulation were the kidney and liver. The effective dose was 0.019 ± 0.004 mSv/MBq. Injection of 1000 µg provided the best standard discrimination between HER2-positive and HER2-low or HER2-negative tumors 2 h after injection (SUVmax 16.9 ± 7.6 vs. 3.6 ± 1.4, p < 0.005). The 99mTc-ZHER2:41071 uptake in HER2-positive lymph node metastases (SUVmax 6.9 ± 2.4, n = 5) was significantly (p < 0.05) higher than that in HER2-low/negative lymph nodes (SUVmax 3.5 ± 1.2, n = 4). 99mTc-ZHER2:41071 visualized hepatic metastases in a patient with liver involvement. Conclusions: Injections of 99mTc-ZHER2:41071 appear safe and exhibit favorable dosimetry. The protein dose of 1000 µg provides the best discrimination between HER2-positive and HER2-low/negative expression of HER2 according to the definition used for current HER2-targeting drugs.© The author(s).