Differences in Fibroinflammatory Activity Shown on Ga-FAPI-04 and F-FDG PET/CT in the Two Subtypes of IgG4-Related Disease.

IgG4-related disease (IgG4-RD) is a highly heterogeneous autoimmune disease. Recently, 2 subtypes of IgG4-RD, proliferative and fibrotic, were defined according to patients' clinicopathologic characteristics. The purpose of this study was to determine the difference in fibroinflammatory activity shown on Ga-FAPI-04 and F-FDG PET/CT in the proliferative and fibrotic IgG4-RD subtypes. Thirty-seven newly diagnosed IgG4-RD patients (29 of the proliferative subtype and 8 of the fibrotic subtype) who had undergone Ga-FAPI-04 and F-FDG PET/CT were enrolled. SUV and target-to-background ratio (TBR) of IgG4-RD lesions were measured. To evaluate the weight of fibroinflammatory activity, the PET index of a lesion was calculated as the quotient of SUV or TBR of Ga-FAPI-04 and that of F-FDG. For the assessment of the global disease in an individual patient, the PET index was defined as the ratio of SUV of all involved lesions in Ga-FAPI-04 PET/CT to that in F-FDG. The F-FDG uptake values of the most prominent lesions in the proliferative and fibrotic subtypes were similar; however, the proliferative subtype showed significantly higher uptake of Ga-FAPI-04 than did the fibrotic subtype (SUV, 17.67 ± 7.46 vs. 10.93 ± 2.22, = 0.005; TBR, 15.49 ± 8.23 vs. 9.25 ± 3.00, = 0.015). The PET index of proliferative-subtype patients was higher than that of fibrotic-subtype patients (1.46 ± 0.41 vs. 1.14 ± 0.39, = 0.039). The PET index of pancreatobiliary disease was significantly higher than that of head-and-neck disease, fibrosis or aortitis, lymph nodes, and another disease subtype ( < 0.05). After first-line treatment, patients with a PET index of at least 1.5 had significantly shorter relapse-free survival than those with a PET index of less than 1.5 (22.0 mo vs. not reached, < 0.0001; hazard ratio, 13.46; 95% CI, 2.236-81.03). The proliferative subtype of IgG4-RD had a greater weight of fibroinflammatory activity than that of the fibrotic subtype. The PET index, a marker of the weight of fibroinflammatory activity, is predictive of relapse-free survival of IgG4-RD.