Prospective Head-to-Head Comparison of 18F-FDG and 68Ga-FAPI PET/CT in De Novo and Recurrent Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

Purpose To compare gallium 68 (68Ga) fibroblast activation protein inhibitor (FAPI) PET/CT with plasma Epstein-Barr virus (EBV)-DNA load measurement, contrast-enhanced MRI/CT, and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT for nasopharyngeal carcinoma (NPC) initial assessment and recurrence surveillance. Materials and Methods Participants with NPC who underwent both 18F-FDG and 68Ga-FAPI PET/CT examinations within 1 week for initial assessment (treatment-naive cohort) and recurrence surveillance (posttreatment cohort) were enrolled in this prospective study conducted between July 2020 and November 2023 (Chinese Clinical Trial Registry identifier no. ChiCTR2100054163). The data of plasma EBV DNA load and contrast-enhanced MRI/CT were analyzed. Diagnostic performance was compared using the McNemar test. The relationships between plasma EBV DNA and the two tracers were assessed by using simple linear regression analysis. Results Sixty-five participants (median age, 50 years [IQR, 41.50-61 years]; 50 male) were included, with 31 in the treatment-naive cohort and 34 in the posttreatment cohort. In participant-level analysis, 68Ga-FAPI PET/CT demonstrated the highest accuracy rate in identifying the participants with de novo (100% [31 of 31] vs 84% [26 of 31], 77% [24 of 31], and 84% [26 of 31], P = .06, .02, and .06, respectively) and recurrent (94% [32 of 34] vs 53% [18 of 34], 68% [23 of 34], and 85% [29 of 34], P = .001, .02, and .25, respectively) NPC, compared with plasma EBV DNA, contrast-enhanced MRI/CT, and 18F-FDG PET/CT. Furthermore, compared with contrast-enhanced MRI/CT and 18F-FDG PET/CT, 68Ga-FAPI PET/CT led to upstaging in five of 31 (16%) and downstaging in four of 31 (13%) treatment-naive participants. Lesion uptake at 68Ga-FAPI PET/CT did not correlate with plasma EBV DNA load (P > .05). Conclusion 68Ga-FAPI PET/CT outperformed plasma EBV DNA level, contrast-enhanced MRI/CT, and 18F-FDG PET/CT in initial assessment and recurrence surveillance of NPC. Keywords: Head/Neck, PET/CT, Nasopharyngeal Carcinoma, Epstein-Barr Virus, Fibroblast Activation Protein Inhibitor, FDG Chinese Clinical Trial Registry identifier no. ChiCTR2100054163 Supplemental material is available for this article. © RSNA, 2026.