68Ga-FAPI PET/CT for assessing fibroblast activation and disease activity in primary Sjögren's disease: a prospective case-control study.

OBJECTIVE: Sjögren's disease (SjD) is an autoimmune exocrinopathy characterized by chronic glandular inflammation. Fibroblast activation protein (FAP) is a promising imaging biomarker for local inflammation. This study aims to evaluate the utility of [68Ga]Ga-FAPI PET/CT in SjD, assess its correlation with disease activity, and explore its role in monitoring treatment response. METHODS: This study enrolled SjD patients (2016 ACR-EULAR criteria), with cancer patients as controls. All SjD participants underwent ESSPRI and ESSDAI assessments and serological testing; labial gland biopsies were additionally performed in a subset. The enrolled patients subsequently underwent longitudinal follow-up. RESULTS: [68Ga]Ga-FAPI-04 PET/CT imaging revealed significantly higher tracer uptake in the lacrimal, parotid, and sublingual glands of SjD patients compared with controls (all p < 0.001), while no significant difference was observed in the submandibular gland. Receiver operating characteristic analysis demonstrated high diagnostic performance, particularly for parotid gland parameters (SUVmax: AUC = 0.89; 95% CI: 0.84-0.94; p < 0.001). After correcting for multiple comparisons, parotid gland uptake remained significantly and positively correlated with ESR (r = 0.51-0.58, p < 0.05) and RF (r = 0.50-0.57, p < 0.05). Regarding disease activity, only parotid total lesion fibroblast activation (TLF) demonstrated a significant correlation with the ESSDAI score (r = 0.48, p < 0.05). Follow-up imaging in nine patients showed that glucocorticoid therapy was associated with concurrent reductions in clinical scores and salivary gland FAPI uptake. CONCLUSION: [68Ga]Ga-FAPI PET/CT noninvasively assesses fibroblast activation in SjD, correlates with disease activity and treatment response, and supports its potential clinical utility. TRIAL REGISTRATION: This study has been registered online at NIH ClinicalTrial.gov (NCT07062523).