[177Lu]Lu-FAPI Radioligand Therapy: Emerging Horizons and Clinical Promise in Solid Tumors: A Comprehensive Review.

Abstract

[¹⁷⁷Lu]Lu-FAPI, a novel and innovative radioligand targeting fibroblast activation protein (FAP), has rapidly emerged as a powerful therapeutic strategy for difficult-to-treat solid malignancies. FAP is highly expressed in cancer-associated fibroblasts (CAFs) across a broad spectrum of solid malignancies, thereby providing a valuable therapeutic target for novel radiopharmaceuticals. To date, a growing body of preliminary studies has explored the therapeutic potential of [¹⁷⁷Lu]Lu-FAPI in oncology, with numerous ongoing clinical trials currently recruiting patients to substantiate its evolving prospects. This comprehensive review critically synthesizes current clinical evidence on [¹⁷⁷Lu]Lu-FAPI radioligand therapy (RLT), outlining its available formulations, therapeutic efficacy, safety profile, recent advancements, challenges, and emerging applications across diverse tumor types. [¹⁷⁷Lu]Lu-FAPI has shown considerable promise as an effective and relatively safe theranostic agent, with particular advantages in combination therapy approaches. Nevertheless, larger, well-controlled clinical studies are essential to establish its long-term efficacy and safety profile. Despite current limitations, this review underscores the emerging role of [¹⁷⁷Lu]Lu-FAPI in oncological care, with growing relevance to personalized oncology strategies, and calls for further investigation to refine its clinical integration and maximize patient-specific outcomes.