成纤维细胞激活蛋白（FAP）在基质细胞和肿瘤细胞（特别是肉瘤）中的独特表达模式，以及其在正常组织中的缺失，使其成为检测和治疗各种癌症类型的有前途的治疗诊断方法。本前瞻性研究的目的是评估 [177Lu]Lu-FAPI-2286 在晚期转移性肉瘤患者中的可行性、安全性、生物分布和治疗效果。 8 名无法切除或出现疾病复发的晚期转移性肉瘤患者常规治疗后，使用[177Lu]Lu-FAPI-2286进行PTRT（肽靶向放射性核素治疗）。治疗前，通过 [68Ga]Ga-FAPI-2286 PET/CT 确认肿瘤摄取。使用 [177Lu]Lu-FAPI-2286 (6660-7400 MBq) 进行四个周期的 PTRT 后，6-8每个周期之间间隔一周，患者中没有观察到3级或4级副作用，并且所有参与者对治疗的耐受性良好。结果显示，原发肿瘤的平均体积减少了 52.37%，同时转移灶的 SUVmax 和 TBR 显着下降（分别为 29.67% 和 43.66%），特别是在肺转移的情况下。此外，除了身体能力的改善外，疼痛也明显减轻，总体生存率提高，患者对治疗的满意度也提高。[177Lu]Lu-FAPI-2286 PTRT，用于多种癌症类型，在肉瘤患者中表现出良好的耐受性，副作用最小，放射性肽在肿瘤内持久保留，并且具有良好的治疗效果。这项前瞻性研究的初步结果需要通过进一步的临床试验来证实。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma.Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [177Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [68Ga]Ga-FAPI-2286 PET/CT.After four cycles of PTRT with [177Lu]Lu-FAPI-2286 (6660-7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUVmax and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients.[177Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.