68Ga-FAPI PET/CT may provide a non-invasive approach to assessing fibroblast activation and disease activity in patients with primary Sjögren’s disease (SjD), according to a recent prospective case-control study published in Rheumatology (Oxford). The imaging modality also showed potential for evaluating treatment response, with reductions in salivary gland FAPI uptake observed alongside clinical improvement following glucocorticoid therapy.
FAPI PET/CT targets fibroblast activation protein expressed by activated fibroblasts involved in tissue remodelling and fibrogenesis. Although the technique was initially developed for cancer imaging, growing evidence has demonstrated its potential in fibroinflammatory and immune-mediated diseases. Unlike 18F-FDG PET/CT, which primarily reflects increased glucose metabolism associated with inflammatory activity, FAPI imaging provides information on fibroblast activation and may offer complementary insights into tissue remodelling and fibrosis.
The prospective study included patients with SjD who fulfilled the 2016 American College of Rheumatology-European Alliance of Associations for Rheumatology classification criteria, with patients with cancer included as controls. Participants with SjD underwent clinical assessment using the EULAR Sjögren’s Syndrome Patient Reported Index and EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), together with serological investigations. Labial salivary gland biopsies were also performed in a subset of patients, and participants underwent longitudinal follow-up.
Imaging with 68Ga-FAPI-04 PET/CT demonstrated significantly greater tracer uptake in the lacrimal, parotid, and sublingual glands among patients with SjD compared with controls, with all comparisons reaching statistical significance (P < 0.001). No significant difference was observed in the submandibular glands.
The parotid gland showed particularly strong diagnostic performance. Receiver operating characteristic analysis demonstrated an area under the curve of 0.89 (95% CI, 0.84–0.94; P < 0.001) for the maximum standardized uptake value (SUVmax). After correction for multiple comparisons, parotid gland FAPI uptake remained significantly and positively associated with erythrocyte sedimentation rate (ESR), with correlation coefficients ranging from 0.51 to 0.58, and rheumatoid factor (RF), with correlation coefficients ranging from 0.50 to 0.57 (P < 0.05).
Among the measures of disease activity evaluated, parotid total lesion fibroblast (TLF) activation was significantly correlated with ESSDAI scores (r = 0.48, P < 0.05). This association suggested that FAPI uptake may reflect clinically relevant disease activity in the salivary glands.
The longitudinal findings further supported the potential role of FAPI PET/CT in treatment monitoring. In nine patients who underwent follow-up imaging, glucocorticoid treatment was associated with reductions in clinical disease activity measures accompanied by decreases in FAPI uptake in the salivary glands.
The findings indicate that 68Ga-FAPI PET/CT can visualize fibroblast activation in the major glandular sites affected by SjD and may provide quantitative imaging measures associated with systemic inflammatory markers and disease activity. The observed changes following glucocorticoid treatment also suggest that FAPI PET/CT could have a role in monitoring treatment response. Further studies involving larger patient populations and longer follow-up will be needed to establish the clinical value of FAPI PET/CT in SjD and determine how it could complement existing clinical, serological, and histopathological assessments.
References
- Wang J, Jia Y, Xiang J, Lin K, Wang R, Wang Y, Chen J, Luo Y, Fei Y, Zhu Z. 68Ga-FAPI PET/CT for assessing fibroblast activation and disease activity in primary Sjögren’s disease: a prospective case-control study. Rheumatology (Oxford). 2026 Sep 1;65(9):keag440.
- Jenabi E, Hotta M, Atzinger A, Volkmann E, Jung T, Bailly M, Pirich C, Calais J, Kuwert T, Beheshti M. The Role of FAPI PET/CT in the Assessment of Inflammatory Diseases. Semin Nucl Med. 2026 Jul;56(4):685-701.