The goal of this study was to characterize the relationship between tumor uptake of ⁶⁴Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including ¹⁸F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2−) based on fluorescence in situ hybridization (FISH)–supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent ⁶⁴Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21–25 (day 1) and 47–49 (day 2) h after ⁶⁴Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUV_max. Average intrapatient SUV_max (<SUV_max>_pt) was compared between HER2+ and HER2− patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2− (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median <SUV_max>_pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2− patients (P < 0.005 either day). The distributions of <SUV_max>_pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2− disease (P < 0.005 and 0.001, respectively, on days 1 and 2). Conclusion: By 1 d after injection, uptake of ⁶⁴Cu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2− groups, suggests a role for ⁶⁴Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.

本研究的目的是表征通过 PET/CT 测量的⁶⁴ Cu-DOTA-曲妥珠单抗的肿瘤摄取与标准的、基于免疫组织化学 (IHC) 的人表皮生长因子受体 2 (HER2) 状态的组织病理学分类之间的关系。患有转移性乳腺癌 (MBC) 的女性。方法：活检证实为 MBC 且未接受曲妥珠单抗治疗 2 个月或更长时间的女性接受完整分期，包括¹⁸ F-FDG PET/CT。根据活检肿瘤组织的荧光原位杂交 (FISH) 补充免疫组织化学，将患者分为 HER2 阳性 (HER2+) 或阴性 (HER2-)。18 名患者接受了⁶⁴Cu-DOTA-曲妥珠单抗注射液，在 16 例之前通过曲妥珠单抗输注（45 毫克）。在注射⁶⁴ Cu-DOTA-曲妥珠单抗后 21-25（第 1 天）和 47-49（第 2 天）进行 PET/CT 。显着病变中的放射性标记摄取被测量为 SUV _max。在 HER2+ 和 HER2- 患者之间比较平均患者内 SUV _max (<SUV _max > _pt )。结果： 11 名女性为 HER2+（8 名免疫组织化学 3+；3 名免疫组织化学 2+/FISH 扩增），而 7 名女性为 HER2-（3 名免疫组织化学 2+/FISH 未扩增；4 名免疫组织化学 1+）。中值 <SUV _max > _pt对于 HER 2+ 患者，第 1 天和第 2 天分别为 6.6 和 6.8 g/mL，对于 HER2− 患者为 3.7 和 4.3 g/mL（任一天P < 0.005）。<SUV _max > _pt的分布在两组之间重叠，HER2+ 的患者间变异性大于 HER2- 疾病（第1 天和第 2 天的P < 0.005 和 0.001，分别）。结论：注射后 1 天，MBC中⁶⁴ Cu-DOTA-曲妥珠单抗的摄取与患者 HER2 状态密切相关，并且表明与 HER2 结合。HER2+ 患者内部和之间的变异性，以及 HER2+ 和 HER2− 组之间的重叠，表明⁶⁴Cu-DOTA-trastuzumab PET/CT 在优化包括曲妥珠单抗在内的治疗中。