Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
J Nucl Med. 2023 Sep;64(9):1364-1370. doi: 10.2967/jnumed.122.265364. Epub 2023 Jul 13.
Imaging using the human epidermal growth factor receptor 2 (HER2)-binding tracer Ga-labeled Z-Cys-MMA-DOTA ([Ga]Ga-ABY-025) was shown to reflect HER2 status determined by immunohistochemistry and in situ hybridization in metastatic breast cancer (MBC). This single-center open-label phase II study investigated how [Ga]Ga-ABY-025 uptake corresponds to biopsy results and early treatment response in both primary breast cancer (PBC) planned for neoadjuvant chemotherapy and MBC. Forty patients with known positive HER2 status were included: 19 with PBC and 21 with MBC (median, 3 previous treatments). [Ga]Ga-ABY-025 PET/CT, [F]F-FDG PET/CT, and core-needle biopsies from targeted lesions were performed at baseline. [F]F-FDG PET/CT was repeated after 2 cycles of therapy to calculate the directional change in tumor lesion glycolysis (Δ-TLG). The largest lesions (up to 5) were evaluated in all 3 scans per patient. SUVs from [Ga]Ga-ABY-025 PET/CT were compared with the biopsied HER2 status and Δ-TLG by receiver operating characteristic analyses. Trial biopsies were HER2-positive in 31 patients, HER2-negative in 6 patients, and borderline HER2-positive in 3 patients. The [Ga]Ga-ABY-025 PET/CT cutoff SUV of 6.0 predicted a Δ-TLG lower than -25% with 86% sensitivity and 67% specificity in soft-tissue lesions (area under the curve, 0.74 [95% CI, 0.67-0.82]; = 0.01). Compared with the HER2 status, this cutoff resulted in clinically relevant discordant findings in 12 of 40 patients. Metabolic response (Δ-TLG) was more pronounced in PBC (-71% [95% CI, -58% to -83%]; < 0.0001) than in MBC (-27% [95% CI, -16% to -38%]; < 0.0001), but [Ga]Ga-ABY-025 SUV was similar in both with a mean SUV of 9.8 (95% CI, 6.3-13.3) and 13.9 (95% CI, 10.5-17.2), respectively ( = 0.10). In multivariate analysis, global Δ-TLG was positively associated with the number of previous treatments ( = 0.0004) and negatively associated with [Ga]Ga-ABY-025 PET/CT SUV ( = 0.018) but not with HER2 status ( = 0.09). [Ga]Ga-ABY-025 PET/CT predicted early metabolic response to HER2-targeted therapy in HER2-positive breast cancer. Metabolic response was attenuated in recurrent disease. [Ga]Ga-ABY-025 PET/CT appears to provide an estimate of the HER2 expression required to induce tumor metabolic remission by targeted therapies and might be useful as an adjunct diagnostic tool.
使用人表皮生长因子受体 2（HER2）结合示踪剂 Ga 标记的 Z-Cys-MMA-DOTA ([Ga]Ga-ABY-025）进行的成像显示，转移性乳腺癌（MBC）中 HER2 状态与免疫组织化学和原位杂交确定的 HER2 状态一致。这项单中心开放标签 II 期研究调查了 [Ga]Ga-ABY-025 摄取与原发性乳腺癌（PBC）中计划接受新辅助化疗的原发性乳腺癌（PBC）和 MBC 的活检结果和早期治疗反应之间的对应关系。 40 名已知 HER2 状态阳性的患者入组：19 名 PBC 和 21 名 MBC（中位数，3 次既往治疗）。在基线时进行了[Ga]Ga-ABY-025 PET/CT、[F]F-FDG PET/CT 和靶向病变的核心针活检。在治疗 2 个周期后重复[F]F-FDG PET/CT，以计算肿瘤病变糖酵解的方向变化（Δ-TLG）。每个患者的所有 3 次扫描中最多评估 5 个最大的病变。通过接受者操作特征分析比较[Ga]Ga-ABY-025 PET/CT 的 SUV 与活检的 HER2 状态和 Δ-TLG。 在 31 名患者中，试验活检为 HER2 阳性，6 名患者为 HER2 阴性，3 名患者为边界 HER2 阳性。[Ga]Ga-ABY-025 PET/CT 的 SUV 截断值为 6.0，预测 Δ-TLG 低于-25%，灵敏度为 86%，特异性为 67%（软组织病变的曲线下面积，0.74 [95%CI，0.67-0.82]； = 0.01）。与 HER2 状态相比，该截断值导致 40 名患者中有 12 名存在临床相关的不一致发现。代谢反应（Δ-TLG）在 PBC 中更为明显（-71% [95%CI，-58%至-83%]； < 0.0001），而在 MBC 中为-27%（95%CI，-16%至-38%）； < 0.0001），但[Ga]Ga-ABY-025 SUV 在两者之间相似，平均 SUV 分别为 9.8（95%CI，6.3-13.3）和 13.9（95%CI，10.5-17.2）（ = 0.10）。多变量分析显示，全球 Δ-TLG 与既往治疗次数呈正相关（ = 0.0004），与 [Ga]Ga-ABY-025 PET/CT SUV 呈负相关（ = 0.018），但与 HER2 状态无关（ = 0.09）。[Ga]Ga-ABY-025 PET/CT 预测了 HER2 阳性乳腺癌中 HER2 靶向治疗的早期代谢反应。在复发性疾病中，代谢反应减弱。[Ga]Ga-ABY-025 PET/CT 似乎提供了对 HER2 表达的估计，通过靶向治疗诱导肿瘤代谢缓解所需的 HER2 表达，并且可能作为一种有用的辅助诊断工具。
