[⁶⁸Ga]Ga-FAPI-04 PET/CT for subtyping and prognostication of IgG4-related disease

Recently, two subtypes of immunoglobulin G4-related disease (IgG4-RD), proliferative type and fibrotic type, were defined according to patients' clinicopathological characteristics. The objective of this study is to determine the difference of fibrotic activity shown in [⁶⁸Ga]Ga-FAPI-04 PET/CT in these two subtypes of IgG4-RD.

Sixty-eight IgG4-RD patients (50 proliferative subtype, 18 fibrotic subtype; 47 newly diagnosed treatment-naïve, 21 with relapsed or persistent disease after treatment) who underwent [⁶⁸Ga]Ga-FAPI-04 PET/CT were enrolled. The SUVmax and target-to-background ratio (TBR) were measured in IgG4-RD lesions. Metabolic lesion volume (MLV) and total lesion uptake (TLU) were obtained from the MIM workstation, and SUVmean of the global lesions was calculated as the quotient of TLU and MLV (SUVmean = TLU/MLV). Proliferative subtype of IgG4-RD showed significantly higher uptake of [⁶⁸Ga]Ga-FAPI-04 than the fibrotic subtype (SUVmax, 16.59 ± 7.06 vs. 12.08 ± 4.65, P = 0.007; TBR, 14.50 ± 7.98 vs. 10.32 ± 5.08, P = 0.036). The TLU and MLV were also significantly higher in the proliferative subtype (median [IQR], TLU, 861.40 [340.40, 2465.48] vs. 419.15 [244.98, 657.90], P = 0.020; MLV, 177.11 [79.99, 503.94] vs. 107.98 [54.10, 163.24], P = 0.029). The pancreato-hepato-biliary disease demonstrated the highest SUVmax and TBR, followed by fibrosis/periaortitis, head-and-neck disease, and others involvements (P < 0.05). Lymph nodes demonstrated the lowest SUVmax and TBR among all disease. The relapse-free survival curve did not show significant difference between proliferative and fibrotic patients (P = 0.56). Patients with TBR ≥ 16.3 or SUVmean ≥ 5 had significantly shorter relapse-free survival than those below these thresholds (TBR, 39.7 months vs. not reached, P = 0.0078, hazard ratio = 5.74 [95%CI, 1.58-20.80]; SUVmean, 39.0 months vs. not reached, P = 0.019, hazard ratio = 4.36 [95%CI, 1.27-14.94]).

The proliferative subtype of IgG4-RD exhibited more dominant uptake of [⁶⁸Ga]Ga-FAPI-04 than the fibrotic subtype, suggesting greater fibrotic disease burden. [⁶⁸Ga]Ga-FAPI-04 PET/CT derived parameters is predictive of relapse-free survival in patients with IgG4-RD.

ClinicalTrials. NCT04125511 (Characterizing IgG4RD With 68GaFAPI PET/CT). Registered 14 October 2019, https//clinicaltrials.gov/study/NCT04125511?cond=NCT04125511&rank=1.