Abstract
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.