在包括转移性乳腺癌在内的多种癌症中观察到成纤维细胞激活蛋白（FAP）表达上调，这促使人们研究用于诊断和治疗目的的小分子抑制剂。虽然使用 68 Ga 或 18F 标记的 FAPi 单体进行 PET/CT 成像在乳腺癌诊断中的诊断价值已得到证实，但仍迫切需要治疗类似物。这项回顾性研究旨在评估 [177Lu]Lu-DOTAGA.FAPi 二聚体放射性核素治疗对于既往接受过 [68 Ga]Ga-DOTA.SA.FAPi PET/CT 扫描的晚期乳腺癌患者的安全性和有效性。确认FAP的表达。2020年11月至2023年3月期间，采用富有同情心的治疗方法对经过重度治疗的晚期乳腺癌患者进行[177Lu]Lu-DOTAGA.FAPi二聚体放射性核素治疗。 19 名转移性乳腺癌患者（18 名女性，1 名男性）参与了这项研究，平均年龄为 44.6±10.7 岁。治疗间隔为 8 至 12 周，中位随访时间为 14 个月。该研究的主要目的是使用 [68 Ga]Ga-DOTA.SA.FAPi PET/CT 扫描评估分子反应，并根据 PERCIST 标准进行反应评估。次要终点包括总生存期 (OS)、无进展生存期 (PFS)、临床反应评估和使用 CTCAE v5.0 指南的安全性评估。总共进行了 65 个周期，平均累积活性为 19 ± 5.7 GBq（ [177Lu]Lu-DOTAGA.FAPi 二聚体的范围为 510±±154 mCi)，范围为 11 至 33.3 GBq（300 至 900 mCi）。周期数从 2 到 6 不等，中位数为 3 个周期。治疗方案包括对患者进行不同数量的周期：具体而言，五名患者接受两个周期，九名患者接受三个周期，一名患者接受四个周期，四名患者接受六个周期。大多数患者患有浸润性/浸润性导管癌（94.7%），而一小部分患者患有浸润性小叶癌（5.3%）。所有患者均出现骨转移，其中 5 例伴有肝脏转移，7 例出现脑转移。使用 [68 Ga]Ga-DOTA.SA.FAPi PET/CT 扫描进行的疗效评估显示，所评估的 16 名患者中有 25% 获得部分缓解，而 37.5% 则出现疾病进展。根据VAS缓解标准，26.3%达到完全缓解，15.7%有部分缓解，42%显示最小缓解，11%疾病稳定，5%无缓解。临床疾病控制率良好，95%的患者实现疾病控制。临床客观缓解率为84%。中位随访期为 14 个月。在分析时，中位总生存期为 12 个月，中位无进展生存期为 8.5 个月。值得注意的是，在研究期间没有观察到严重的血液学、肾或肝毒性、电解质失衡或3级或4级不良事件。研究结果表明[177Lu]Lu-DOTAGA.FAPi二聚体治疗耐受性良好、安全、对治疗终末期转移性乳腺癌患者有效。 [177Lu]Lu-DOTAGA.FAPi 二聚体治疗在晚期乳腺癌患者中表现出良好的疗效，疾病控制率高、反应结果良好、安全性可接受。需要进一步的研究和更长时间的随访来评估长期结果并验证这些发现。© 2023。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

The upregulation of fibroblast activation protein (FAP) expression has been observed in various cancers, including metastatic breast carcinoma, prompting research into small molecule inhibitors for both diagnostic and therapeutic purposes. While the diagnostic value of PET/CT imaging using 68 Ga- or 18F-labelled FAPi-monomers in breast cancer diagnosis is well-established, there is a significant need for therapeutic analogs. This retrospective study aimed to assess the safety and effectiveness of [177Lu]Lu-DOTAGA.FAPi dimer radionuclide therapy in patients with advanced-stage breast cancer who had previously undergone [68 Ga]Ga-DOTA.SA.FAPi PET/CT scans to confirm the expression of FAP.Between November 2020 and March 2023, a compassionate treatment approach was utilized to administer [177Lu]Lu-DOTAGA.FAPi dimer radionuclide therapy to heavily pretreated patients with advanced breast cancer. Nineteen patients (18 females, 1 male) with metastatic breast cancer participated in the study, with an average age of 44.6 ± 10.7 years. The therapy was administered at intervals of 8 to 12 weeks, and the median follow-up duration was 14 months. The primary objective of the study was to assess molecular response using [68 Ga]Ga-DOTA.SA.FAPi PET/CT scans, with response evaluation based on the PERCIST criteria. Secondary endpoints included overall survival (OS), progression-free survival (PFS), clinical response assessment, and safety evaluation using CTCAE v5.0 guidelines.A total of 65 cycles were administered, with a mean cumulative activity of 19 ± 5.7 GBq (510 ± 154 mCi) ranging from 11 to 33.3 GBq (300 to 900 mCi) of [177Lu]Lu-DOTAGA.FAPi dimer. The number of cycles ranged from 2 to 6, with a median of 3 cycles. The treatment protocol consisted of different numbers of cycles administered to the patients: specifically, two cycles were given to five patients, three cycles to nine patients, four cycles to one patient, and six cycles to four patients. Most patients had invasive/infiltrative ductal carcinoma (94.7%), while a small percentage had invasive lobular carcinoma (5.3%). All patients had bone metastases, and five of them also had liver involvement, while seven had brain metastases. Response assessment using [68 Ga]Ga-DOTA.SA.FAPi PET/CT scans showed that 25% of the 16 patients evaluated had partial remission, while 37.5% exhibited disease progression. According to the VAS response criteria, 26.3% achieved complete response, 15.7% had partial response, 42% showed minimal response, 11% had stable disease, and 5% had no response. The clinical disease control rate was promising, with 95% of patients achieving disease control. The clinical objective response rate was 84%. The median follow-up period was 14 months. At the time of analysis, the median overall survival was 12 months, and the median progression-free survival was 8.5 months. Notably, no severe hematological, renal, or hepatic toxicities, electrolyte imbalances, or adverse events of grade 3 or 4 were observed during the study.The findings suggest that [177Lu]Lu-DOTAGA.FAPi dimer therapy is well-tolerated, safe, and effective for treating end-stage metastatic breast cancer patients. [177Lu]Lu-DOTAGA.FAPi dimer treatment demonstrated promising efficacy in patients with advanced breast cancer, as indicated by high disease control rates, favorable response outcomes, and acceptable safety profile. Further research and longer follow-up are warranted to assess long-term outcomes and validate these findings.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.