Exploratory Analysis of [ 68 Ga]Ga-FAP-2286 PET/CT Quantitative Parameters for Predicting Response to [ 177 Lu]Lu-FAP-2286 Therapy in Non-small Cell Lung Cancer.

[BACKGROUND] This exploratory study aimed to assess the prognostic value of quantitative parameters derived from [ 68 Ga]Ga-FAP-2286 PET/CT in predicting treatment response to [ 177 Lu]Lu-FAP-2286 radioligand therapy in patients with non-small cell lung cancer (NSCLC).

[PATIENTS AND METHODS] Patients with histologically confirmed NSCLC underwent [ 68 Ga]Ga-FAP-2286 PET/CT before and after 2 cycles of [ 177 Lu]Lu-FAP-2286 therapy. Based on clinical outcomes, patients were classified as responders or nonresponders. Quantitative PET/CT parameters-including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF), and tumor-to-background ratio (TBR)-were evaluated. Progression-free survival (PFS) and overall survival (OS) were compared using the Kaplan-Meier method and log-rank test.

[RESULTS] In this cohort of 18 NSCLC patients, baseline PET parameters, including FTV, TLF, and TBR, were significant predictors. Interval PET parameters, such as SUVmax, FTV, TLF, and TBR, were significant predictors of treatment response. In addition, ΔPET parameters ΔSUVmax, ΔFTV, and ΔTLF also correlated with therapeutic outcomes. The responder group had a median progression-free survival (mPFS) of 14.4 months, while the nonresponder group had an mPFS of 7.15 months. The OS for the responder group was not reached, whereas the nonresponder group exhibited an OS of 12 months.

[CONCLUSIONS] Quantitative parameters derived from [ 68 Ga]Ga-FAP-2286 PET/CT are valuable predictors of [ 177 Lu]Lu-FAP-2286 treatment efficacy in NSCLC patients. Dynamic monitoring of these metrics allows for early identification of treatment responses and supports personalized therapy strategies.