Comparative Evaluation of [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT in Metastatic Breast and Lung Cancer: Semiquantitative, Volumetric and Prognostic Assessment

Objective: To compare metastatic lesion detection on [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT in metastatic breast and lung cancers and to assess the relationship between PET-derived imaging parameters and progression-free survival (PFS). Methods: In this prospective dual-cohort study, 45 patients (23 breast cancer, 22 lung adenocarci-noma) underwent paired [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT within four weeks. Semiquantitative (SUVmax, SUVmean) and volumetric (MTV, TLG, STV, TLF) PET parameters were measured. Metastatic detection was compared, and correlations with PFS were assessed. Results: In breast cancer [18F]FDG demonstrated higher primary tu-mor uptake, whereas 68Ga-FAPi showed lower background activity, resulting in higher tumor-to-background ratios for brain and bone metastases. Whole-body volumetric indi-ces (wbTLG, wbTLF) showed strong inverse correlations with PFS. In lung adenocarcino-ma, volumetric FAPi-derived parameters (wbTLF, wbSTV) demonstrated modest but sig-nificant correlations with PFS. [68Ga]Ga-DOTA.SA.FAPi PET/CT detected more brain me-tastases than [18F]FDG PET/CT in both cohorts (breast: 15/15 vs. 8/15; lung: 14/14 vs. 4/14). Conclusions: [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT provide comple-mentary diagnostic and prognostic information. In metastatic breast cancer, FAPi-derived volumetric parameters strongly correlate with PFS and improve detection of brain metas-tases. In lung adenocarcinoma, [68Ga]Ga-DOTA.SA.FAPi PET/CT offers low background uptake and prognostically relevant stromal metrics. These findings support a potential role for integrating [68Ga]Ga-DOTA.SA.FAPi PET/CT into disease staging, prognostica-tion, and treatment monitoring. This study did not involve prospective assignment to health-related interventions and therefore did not require clinical trial registration.