Fibroblast-like synoviocyte–targeted PET with 18F-FAPI‑42 for imaging rheumatoid arthritis: Comparison to 18F-FDG PET/MR

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease involving multiple peripheral joints. Activated fibroblast-like synoviocytes with high fibroblast activation protein (FAP) expression are a key component in the development of RA. This study aimed to compare the performance of ¹⁸F-FAP inhibitor (FAPI)-42 PET/CT or PET/MR to ¹⁸F-FDG PET/MR in RA.

Methods: Ten patients with RA were prospectively recruited in this study. They underwent whole-body ¹⁸F-FDG PET/MR and ¹⁸F-FAPI-42 PET/CT (n = 7) or PET/MR (n = 3). PET/MR scans included T1-weighted fast spin echo (FSE) and fat-suppressed T2-weighted FSE or Short Tau Inversion Recovery images covering bilateral temporomandibular joints, hands and wrists, shoulders, hips, knees, ankles and feet. MR images were evaluated for the presence or absence of synovitis, bone marrow edema (BME), and bone erosion in 78 joints. PET images were evaluated for ¹⁸F-FDG and ¹⁸F-FAPI-42 uptake by positive uptake and target-to-background ratio (TBR defined as a ratio between the joint SUV_max normalized by the SUV_max of blood pool at the descending aorta) in 78 joints.

Results: In 10 patients with RA, the median joint counts of positive FAPI uptake and FDG uptake had no significant difference (15 [interquartile range, IQR 5, 24] vs. 12 [IQR 4, 19]). ¹⁸F-FDG PET/MR detected 164/633 (25.9%) joints with MR synovitis, 98/633 (15.5%) with MR BME, 136/633 (21.5%) with MR bone erosion, and 142/780 (18.2%) with positive FDG uptake. ¹⁸F-FAPI PET detected 172/762 (22.6%) joints with positive FAPI uptake. FAPI and FDG positivity showed high agreement (κ = 0.728, P < 0.001). TBRs of FAPI positively correlated with TBRs of FDG (r = 0.711, P < 0.001). The median TBRs of FAPI were significantly higher than TBRs of FDG in joints with MR synovitis, BME, and bone erosion (2.62 [IQR 0.95, 4.34] vs. 1.83 [IQR 1.08, 3.72] for MR synovitis; 2.83 [IQR 1.06, 5.15] vs. 2.05 [IQR 1.19, 3.69] for MR BME; 2.54 [IQR 0.68, 4.56] vs. 1.92 [IQR 0.95, 3.90] for MR bone erosion, P < 0.01 for all).

Conclusions: In this pilot study, ¹⁸F-FAPI-42 PET showed agreement with ¹⁸F-FDG PET for detecting joint involvement in rheumatoid arthritis and had higher TBR than ¹⁸F-FDG PET. Whole-body ¹⁸F-FAPI-42 PET/MR is a promising tool for the evaluation of disease activity in patients with RA.

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