Is There an Added Value of Dual-Time-Point [68Ga]Ga–Fibroblast Activation Protein Inhibitor (FAPI) PET/CT in Differentiating Malignant and Benign Uptake Findings?

Background: [68Ga]Ga-FAPI PET/CT demonstrates high sensitivity for tumor detection but limited specificity because benign fibro-inflammatory conditions may also show tracer uptake. Dual-time-point imaging has been proposed to improve lesion characterization by assessing temporal changes in uptake. This study evaluated whether delayed imaging provides incremental diagnostic value over standard early imaging. Methods: This retrospective lesion-based study evaluated dual-time-point [68Ga]Ga-FAPI PET/CT imaging. SUVmax, maximal tumor-to-background ratio (TBRmax), metabolic tumor volume (MTV), and total lesion uptake (TLU) were measured on early and delayed scans. Diagnostic performance for differentiating malignant from benign uptake findings was assessed using receiver operating characteristic analysis. Results: A total of 123 patients underwent dual-time-point imaging at approximately 26 and 65 min post-injection. Overall, 620 [68Ga]Ga-FAPI uptake findings were analyzed, including 307 malignant uptake findings and 313 benign findings. SUVmax decreased significantly over time in both malignant and benign uptake findings, with a greater decline in benign findings (%ΔSUVmax −7.7% vs. −3.6%, p = 0.0045). TBRmax increased modestly in malignant uptake findings, while MTV and TLU remained largely stable. SUVmax and TBRmax were significantly higher in malignant uptake at both imaging time points; however, diagnostic performance remained moderate (AUCs of 0.65–0.69) due to substantial overlap between lesion types. Delayed imaging did not improve diagnostic accuracy compared with early imaging, and delta parameters demonstrated poor performance (AUC ~0.5). Similar findings were observed across tumor subgroups. Conclusions: In this lesion-based retrospective cohort, delayed dual-time-point [68Ga]Ga-FAPI PET/CT did not demonstrate meaningful incremental diagnostic value over early imaging. A standard early acquisition appears adequate for routine practice, although lesion interpretation remains dependent on clinical, morphologic, and, when needed, histopathologic correlation.