Complementary Roles of 68Ga-FAPI and 18F-FDG PET/CT in Evaluating IgG4-Related Disease: A Systematic Review and Pooled Analysis

1.1. Background IgG4-related disease (IgG4-RD) lacks standardized imaging criteria. This study systematically reviewed head-to-head comparisons of ⁶⁸ Ga-FAPI and ¹⁸ F-FDG PET/CT to clarify their complementary roles in diagnosing and staging IgG4-RD. 1.2. Main body Three high-quality studies (n = 90) were pooled. ⁶⁸ Ga-FAPI showed significantly higher SUVmax and target-to-background ratios (TBR) in parenchymal organs (pancreas, salivary glands) vs ¹⁸ F-FDG ( P  < 0.001), offering superior lesion contrast. While ¹⁸ F-FDG detected more lymph node activity, ⁶⁸ Ga-FAPI identified 136 vs 78 total lesions, improving systemic burden assessment. Pathology correlated FAPI with fibrosis and FDG with inflammation, defining a "flip-flop" pattern. A FAPI/FDG ratio ≥ 1.5 predicted relapse risk. 1.3. Conclusion ⁶⁸ Ga-FAPI excels in parenchymal organ involvement, while FDG highlights inflammatory lymphadenopathy. Combining both tracers enables multimodal evaluation of fibroinflammatory activity, guiding personalized management and prognostication in IgG4-RD.