Feasibility and therapeutic potential of [¹⁷⁷Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma

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.

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.

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 SUV_max 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.

[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.