Differences in Fibroinflammatory Activity Shown on⁶⁸Ga-FAPI-04 and¹⁸F-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 ⁶⁸Ga-FAPI-04 and ¹⁸F-FDG PET/CT in the proliferative and fibrotic IgG4-RD subtypes. <b>Methods:</b> Thirty-seven newly diagnosed IgG4-RD patients (29 of the proliferative subtype and 8 of the fibrotic subtype) who had undergone ⁶⁸Ga-FAPI-04 and ¹⁸F-FDG PET/CT were enrolled. SUV_max 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_max or TBR of ⁶⁸Ga-FAPI-04 and that of ¹⁸F-FDG. For the assessment of the global disease in an individual patient, the PET index was defined as the ratio of SUV_mean of all involved lesions in ⁶⁸Ga-FAPI-04 PET/CT to that in ¹⁸F-FDG. <b>Results:</b> The ¹⁸F-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 ⁶⁸Ga-FAPI-04 than did the fibrotic subtype (SUV_max, 17.67 ± 7.46 vs. 10.93 ± 2.22, <i>P</i> = 0.005; TBR, 15.49 ± 8.23 vs. 9.25 ± 3.00, <i>P</i> = 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, <i>P</i> = 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 (<i>P</i> < 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, <i>P</i> < 0.0001; hazard ratio, 13.46; 95% CI, 2.236-81.03). <b>Conclusion:</b> 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.