Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Solna, Sweden;
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
J Nucl Med. 2024 May 1;65(5):700-707. doi: 10.2967/jnumed.123.266847.
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 [Ga]Ga-ABY-025 for visualization of HER2-low mBC. A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [Ga]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 [Ga]Ga-ABY-025. The SUV 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. Ten patients with HER2-low mBC underwent [Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [Ga]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 and 1 in a liver metastasis with a high SUV but a "cold" core. The visualization of HER2-low mBC with [Ga]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 [Ga]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.
患者 HER2 低转移性乳腺癌（mBC），定义为免疫组织化学（IHC）评分 1+或 2+而无 HER2 基因扩增，可能受益于 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个临床挑战。我们旨在研究使用 [Ga]Ga-ABY-025 进行 HER2 特异性 PET 成像以可视化 HER2 低 mBC 的可行性和安全性。这项前瞻性试点研究纳入了 10 名患有 HER2 低 mBC 的患者，这是一项在表达 HER2 的实体瘤中使用 [Ga]Ga-ABY-025 进行的 2 期篮子成像研究的一部分。患者在瑞典斯德哥尔摩卡罗林斯卡大学医院的乳腺科招募。在注射 200MBq [Ga]Ga-ABY-025 后 3 小时采集 PET/CT 图像。SUV 用于定量示踪剂摄取。超声引导下的肿瘤活检由 HER2 PET 的结果指导。主要结局是评估 HER2 低 mBC 患者中 HER2 PET 的安全性和可行性，通过检测可能与程序相关的不良事件的发生情况来测量。10 名 HER2 低 mBC 患者接受了 [Ga]Ga-ABY-025 PET/CT 检查，并对肿瘤活检进行了配对。未发生不良事件。在所有患者中，均观察到[Ga]Ga-ABY-025 摄取具有实质性的个体内和个体间异质性的摄取。在 10 名具有 ABY-025 摄取病变的患者中，8 名患者的相应病变的 HER2 低状态通过 IHC 或原位杂交得到证实。两名患者的肿瘤活检 IHC 评分为 0：1 例为低 SUV 的皮肤病变，1 例为高 SUV 的肝转移灶，但存在“冷”核心。使用 [Ga]Ga-ABY-025 PET/CT 可视化 HER2 低 mBC 是可行且安全的。示踪剂摄取区域的 HER2 表达水平不同。[Ga]Ga-ABY-025 摄取的观察到的个体内和个体间异质性表明，HER2 PET 可能被用作非侵入性评估疾病异质性的工具，并且有潜力识别出可能从 HER2 靶向药物中获益的患者。
