Fibroblast activation protein (FAP)-binding radiopharmaceuticals have emerged as promising candidates for both diagnostic and therapeutic applications in oncology due to their selective targeting of cancer-associated fibroblasts (CAFs). This review evaluates the current literature on the therapeutic use of FAP-targeted radiopharmaceuticals in human studies, with a focus on their safety, efficacy, and clinical applicability. Data on radionuclide type, clinical outcome, radiological and metabolic response and adverse events were extracted and summarized. The included studies demonstrated that lutetium-177,yttrium-90 and actinium-225 (in combination therapy) labeled FAP inhibitors exhibit high tumor uptake, with varying but mostly sufficient retention and a favorable safety profile. While mild adverse events such as fatigue, nausea and grade 1 or 2 hematotoxicity were observed, severe toxicities were rare. FAPI-based radionuclide therapies generally show high disease control rates, with promising results from tandem and combination strategies. The heterogeneity of tumor types and small sample sizes limited the generalizability of findings. FAP-targeted radioligand therapy appears to be a promising treatment option for patients with advanced cancer who have exhausted standard therapies. However, further large-scale, prospective clinical trials are necessary to determine optimal dosing strategies, long-term safety and efficacy across different tumor types. Emerging approaches, such as covalently binding FAP-targeted radiopharmaceuticals and the use of alpha-emitters such as actinium-225, lead-212 and bismuth-213, may further enhance treatment outcomes and warrant future investigation.
成纤维细胞活化蛋白（FAP）靶向放射性药物因其对癌症相关成纤维细胞（CAFs）的选择性靶向能力，已成为肿瘤学诊断和治疗应用中极具前景的候选药物。本文综述了当前关于FAP靶向放射性药物在人体研究中治疗应用的文献，重点关注其安全性、有效性和临床适用性。研究提取并总结了放射性核素类型、临床结局、影像学与代谢反应及不良事件等数据。纳入的研究表明，镥-177、钇-90和锕-225（联合治疗）标记的FAP抑制剂均表现出较高的肿瘤摄取率，其滞留时间虽有差异但总体充足，且安全性良好。虽然观察到疲劳、恶心及1-2级血液毒性等轻度不良事件，但严重毒性反应罕见。基于FAPI的放射性核素治疗普遍显示出较高的疾病控制率，其中串联治疗与联合治疗策略的结果尤为可观。肿瘤类型的异质性和小样本量限制了研究结果的普适性。对于已用尽标准治疗的晚期癌症患者，FAP靶向放射性配体疗法似乎是一种有前景的治疗选择。然而，仍需进一步开展大规模前瞻性临床试验，以确定不同肿瘤类型的最佳给药策略、长期安全性和疗效。新兴技术如共价结合型FAP靶向放射性药物，以及锕-225、铅-212和铋-213等α发射体的应用，可能进一步提升治疗效果，值得未来深入研究。
肿瘤(癌症)患者之家