背景:成纤维细胞活化蛋白(FAP)在基质和肿瘤细胞中的独特表达模式,特别是在肉瘤中,以及它在正常组织中的缺失,已将其定位为检测和治疗各种癌症类型的有前途的治疗方法。这项前瞻性研究的目的是评估可行性,安全,生物分布,[177Lu]Lu-FAPI-2286治疗晚期转移性肉瘤的疗效。
方法:8例晚期转移性肉瘤,无法切除或在常规治疗后出现疾病复发的患者,使用[177Lu]Lu-FAPI-2286接受PTRT(肽靶向放射性核素治疗)。在治疗之前,通过[68Ga]Ga-FAPI-2286PET/CT获得肿瘤摄取的确认。
结果:在使用[177Lu]Lu-FAPI-2286(6660-7400MBq)进行PTRT的四个循环后,每个周期之间有6-8周的间隔,在患者中没有观察到3级或4级副作用,所有参与者对治疗的耐受性都很好。结果显示原发性肿瘤的平均体积减少了52.37%,伴随着转移性病变的SUVmax和TBR的显着下降(分别为29.67%和43.66%),尤其是肺转移病例。此外,除了体能的提高,疼痛明显减轻,总生存率的提高,并提高了对患者报告的治疗满意度。
结论:[177Lu]Lu-FAPI-2286PTRT,用于不同类型的癌症,在肉瘤患者中表现出良好的耐受性,副作用最小,放射性肽在肿瘤内的持久保留,和有希望的治疗效果。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。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: [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.