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Background: Mesenchymal tissue activation plays a key role already in the early phases of development of synovitis and enthesitis. PET/CT imaging with 68Gallium-labelled Fibroblast Activation Protein Inhibitor-04 (68Ga-FAPI-04) enables the visualization of fibroblast activation in vivo and has already been used to track disease activity in inflammatory rheumatic diseases 1-3. To date, however, there are no data on the clinical significance of this imaging modality in psoriatic arthritis (PsA) and its preclinical phase. Objectives: To assess the presence and localisation of activated fibroblasts detected by 68Ga-FAPI-04-PET/CT in the musculoskeletal system of psoriasis patients at high risk of progression and to determine how the presence of a 68Ga-FAPI-04-PET/CT uptake correlates with clinical and musculoskeletal ultrasound (MSUS) findings and with the risk of progression to PsA. Methods: We prospectively enrolled psoriasis patients with arthralgia who underwent consecutive rheumatological examination, MSUS of knee, wrist, and finger joints and entheses at lateral humeral epicondyle, Achilles tendon insertion, and distal patellar tendon insertion, and whole-body 68Ga-FAPI-04-PET/CT imaging. 68Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardized uptake values (SUVmax) and compared to background muscle uptake by the PET/CT Joint Index (JI). (3) We conducted logistic regression analyses to evaluate the correlation between localisation of 68Ga-FAPI-04 uptake and tender joints and entheses as well as with inflammatory findings on MSUS. Furthermore, we performed survival analyses on PsA development in patients with at least 6 months of follow-up. Results: Thirty-six psoriasis patients were enrolled. Mean age was 49.5±12.2 years and 52.8% were women. Our cohort was at high-risk of transition to PsA due to high mean Body Mass Index (30.0 ± 8.5), frequent history of smoking smoking (n=24 (66.6%)), frequent nail (n=5 (13.9%)) and scalp (n=9 (25%)) involvement and family history of psoriasis (n=12 (33.3%)) and rheumatic diseases (n=3 (8.3%)). Mean duration of skin disease and arthralgia was respectively 16.7 ± 16.8 and 3. 8± 3.4 years. 68Ga-FAPI-04 uptake was detected in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) patients, with a mean SUVmax of 3.2 ± 1.8 for joints and 2.9 ± 1.6 for entheses. (Figure 1) Large joints and lower limbs were more often affected. A significant positive correlation was found between 68Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p 68Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA over a 6-month follow-up (p=0.02). (Figure 2B) Conclusion: Substantial fibroblast activation was found in joints and entheses of psoriasis patients with arthralgias and correlated with tenderness at the clinical examination and with a higher risk of transition to PsA. No correlations with MSUS findings were found. These results suggest that fibroblast activation as depicted by 68Ga-FAPI-04-PET/CT imaging predate the onset of clinical and ultrasound signs of inflammation and might predict the development of a clinical PsA. REFERENCES: 1 Lindner T et al. J Nucl Med. 2018;59(9):1415-22. 2 Schmidkonz C et al.. Journal of Nuclear Medicine. 2023. 3 Luo Y et al. Radiology. 2023;307(3):e222052. Acknowledgements: The study was supported by the Deutsche Forschungsgemeinschaft (DFG-FOR2886 PANDORA, CRC1181 Checkpoints for Resolution of Inflammation, Leibniz award to G.S.). Additional funding was received by the Bundesministerium für Bildung und Forschung (project MASCARA, 01EC1903A), the ERC Synergy grant 4D Nanoscope, and the Emerging Fields Initiative MIRACLE of Friedrich-Alexander University Erlangen-Nürnberg. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101007757 (HIPPOCRATES). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. DS was supported by the 2022 GRAPPA Pilot Research Grant. Disclosure of Interests: None declared.
Corte et al. (Sat,) studied this question.