Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody–drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [⁶⁸Ga]Ga-ABY-025 for visualization of HER2-low mBC. Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [⁶⁸Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [⁶⁸Ga]Ga-ABY-025. The SUV_max was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome—the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events. Results: Ten patients with HER2-low mBC underwent [⁶⁸Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [⁶⁸Ga]Ga-ABY-025–avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025–avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUV_max and 1 in a liver metastasis with a high SUV_max but a "cold" core. Conclusion: The visualization of HER2-low mBC with [⁶⁸Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [⁶⁸Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.

HER2 低转移性乳腺癌 (mBC) 患者（定义为免疫组织化学 (IHC) 评分为 1+ 或 2+，且无 HER2 基因扩增）可能会受益于 HER2 抗体-药物偶联物。由于 HER2 表达的空间和时间异质性以及病理报告的差异，确定合适的候选者是一项临床挑战。我们的目的是研究使用 [ ⁶⁸ Ga]Ga-ABY-025 进行 HER2 特异性 PET 成像以实现 HER2 低 mBC 可视化的可行性和安全性。方法：对 10 名 HER2 低 mBC 患者进行了一项前瞻性预研究，作为HER2 表达实体瘤中[ ⁶⁸ Ga]Ga-ABY-025的 2 期篮式成像研究的一部分。患者是在瑞典斯德哥尔摩卡罗林斯卡大学医院的乳腺诊所招募的。注射 200 MBq 的 [ ⁶⁸ Ga]Ga-ABY-025后 3 小时获取 PET/CT 图像。 SUV _max用于量化示踪剂的吸收。超声引导下的肿瘤活检以 HER2 PET 结果为指导。主要结果——HER2 PET 在 HER2 低 mBC 患者中的安全性和可行性，测量了可能与手术相关的不良事件的发生率。结果： 10 名 HER2 低 mBC 患者接受了 [ ⁶⁸ Ga]Ga-ABY-025 PET/CT 和配对肿瘤活检。没有发生不良事件。在所有患者中，[ ⁶⁸ Ga]Ga-ABY-025-狂热病变在示踪剂摄取方面具有显着的个体内和个体间异质性。在 10 名 ABY-025 阳性病变的患者中，有 8 名通过 IHC 或原位杂交证实了相应病变的 HER2 低状态。两名患者的肿瘤活检 IHC 评分为 0：1 分是 SUV _max较低的皮肤病灶，1 分是 SUV _max高但核心为“冷”的肝转移灶。结论： [ ⁶⁸ Ga]Ga-ABY-025 PET/CT显像 HER2-low mBC是可行且安全的。 IHC 上示踪剂摄取区域显示不同水平的 HER2 表达。观察到的 [ ⁶⁸ Ga]Ga-ABY-025 摄取的个体内和个体间异质性表明 HER2 PET 可以用作疾病异质性无创评估的工具，并且有可能识别 HER2 靶向药物可对患者产生影响的患者。临床益处。