First-in-Human Experience of 177Lu-FAPI-2286 Radioligand Therapy in Follicular Dendritic Cell Sarcoma: A Case Report

Background Follicular dendritic cell sarcoma (FDCS) is an uncommon neoplasm with no standardized treatment guidelines. Conventional therapies, including chemotherapy and targeted agents, yield limited benefit in advanced disease. Fibroblast activation protein (FAP)-targeted radioligand therapy (RLT) using ¹⁷⁷ Lu-FAPI-2286 has emerged as a promising theranostic strategy in multiple malignancies, though its role in FDCS remains unexplored. Case Presentation : A 53-year-old female with biopsy-proven FDCS involving the lesser sac and liver was treated with gemcitabine–docetaxel, adriamycin, and pazopanib, with progressive disease after each line. On ⁶⁸ Ga-FAPI-46 PET/CT, her lesions demonstrated intense FAPI uptake. She underwent two cycles of ¹⁷⁷ Lu-FAPI-2286 (150 mCi each, 6 weeks apart). Post-therapy imaging confirmed tumor targeting, and FDG PET/CT after treatment demonstrated decreased metabolic activity with increased necrosis, consistent with partial metabolic response (PERCIST criteria). The therapy was well tolerated without hematological, renal, or hepatic toxicity. Conclusion This is the first reported case of FDCS treated with ¹⁷⁷ Lu-FAPI-2286, demonstrating clinical and metabolic response with excellent safety. FAPI RLT may represent a viable salvage therapy for refractory FDCS and warrants further prospective evaluation.