Posttreatment ⁶⁸Ga-FAP-2286 PET/CT Parameters for Response and Survival Assessment After ¹⁷⁷Lu-FAP-2286 Radioligand Therapy in Advanced Solid Tumors

PURPOSE: Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and represents an emerging target for radioligand therapy (RLT). This study aimed to evaluate treatment outcomes of ¹⁷⁷Lu-FAP-2286 and to investigate whether changes in quantitative parameters on ⁶⁸Ga-FAP-2286 PET/CT are associated with treatment response and survival in patients with advanced solid tumors. METHODS: In this single-center retrospective study, patients with advanced solid tumors who completed 2 cycles of ¹⁷⁷Lu-FAP-2286 therapy and underwent both baseline and posttreatment ⁶⁸Ga-FAP-2286 PET/CT (8-16 wk after therapy) were included. Maximum standardized uptake value (SUVmax) and total tumor volume (TTV) were quantified using semiautomatic whole-body segmentation. Relative changes (ΔSUVmax and ΔTTV) were calculated. RECIST 1.1 served as the clinical reference standard. Receiver operating characteristic analysis assessed the ability of PET-derived changes to discriminate progressive disease. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: Thirty patients (median age, 65 y; range, 23-78 y) completed 2 cycles of ¹⁷⁷Lu-FAP-2286 therapy. According to RECIST 1.1, partial response, stable disease, and progressive disease occurred in 6 (20.0%), 11 (36.7%), and 13 (43.3%) patients, respectively. SUVmax and TTV decreased in 46.7% of patients. ΔSUVmax demonstrated moderate discrimination for RECIST-defined PD (AUC 0.72, P=0.04). Patients with ΔSUVmax <30% had significantly longer PFS than those with ΔSUVmax ≥30% (median 10.3 vs. 4.4 mo; log-rank P<0.001). Median OS was not reached in the ΔSUVmax <30% group compared with 9.8 months in the ΔSUVmax ≥30% group (log-rank P=0.003). In multivariable analysis, ΔSUVmax remained independently associated with PFS (HR: 5.2, 95% CI 1.5-7.8; P=0.010) and OS (HR: 4.3, 95% CI: 1.3-14.1; P=0.015). CONCLUSIONS: In patients with advanced solid tumors treated with 2 cycles of ¹⁷⁷Lu-FAP-2286, posttreatment changes in SUVmax on ⁶⁸Ga-FAP-2286 PET/CT were associated with treatment response and survival, suggesting potential utility as an imaging biomarker for early response assessment and prognostic stratification.