Article
68Ga-FAPI-04 PET/CT reveals increased entheseal and synovial mesenchymal activation in psoriasis patients at risk of transition to psoriatic arthritis
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Authors
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Giulia Corte
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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Armin Atzinger
- Universitätsklinikum Erlangen, Nuklearmedizin, Erlangen
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Alp Temiz
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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Rita Noversa de Sousa
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen; Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Matosinhos, Serviço de Medicina Interna, Matosinhos
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Melek Yalcin-Mutlu
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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Verena Schönau
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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Maria Gabriella Raimondo
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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Arnd Kleyer
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen; Charité-Universitätsmedizin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Torsten Kuwert
- Universitätsklinikum Erlangen, Nuklearmedizin, Erlangen
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Andreas Ramming
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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David Simon
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen; Charité-Universitätsmedizin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Michael Sticherling
- Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen; Uni-Klinikum, Hautklinik, Erlangen
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Christian Schmidkonz
- Universitätsklinikum Erlangen, Nuklearmedizin, Erlangen; Institute for Medical Engineering, Technical University of Applied Sciences Amberg–Weiden, Weiden
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
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Filippo Fagni
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Erlangen; Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie, Erlangen
| Published: | September 18, 2024 |
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Outline
Text
Introduction: Positron-emission tomography/computed tomography with 68Gallium-labelled Fibroblast Activation Protein Inhibitor-04 (68Ga-FAPI-04 PET/CT) enables the visualization of fibroblast activation in vivo in inflammatory rheumatic diseases [1], [2]. However, there are no data yet on the clinical significance of 68Ga-FAPI-04 PET/CT in psoriatic arthritis (PsA) and its preclinical phase.
We assessed presence and localisation of activated fibroblasts detected by 68Ga-FAPI-04-PET/CT in musculoskeletal system of psoriasis patients and evaluated how this correlates with clinical and musculoskeletal ultrasound (MSUS) findings and with the risk of progression to clinical PsA.
Methods: We prospectively enrolled psoriasis patients with arthralgia who underwent a rheumatological examination including MSUS of most relevant joints and entheses and subsequently underwent a 68Ga-FAPI-04-PET/CT imaging. 68Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardized uptake values (SUVmax) and PET/CT Joint Index [2]. Conducting logistic regression analyses we evaluated the correlation between localisation of 68Ga-FAPI-04-PET/CT uptake and tender joints and entheses at clinical examination and with MSUS findings. We furthermore performed survival analyses on patients with at least 6 months of follow-up.
Results: Thirty-six patients were enrolled. Mean age (SD) was 49.5 (12.2) years, 52.8% were women. 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 (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. 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 <0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlation was found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720) (Figure 1A [Fig. 1]). Patients with relevant synovio-entheseal 68Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA over a 6 months follow-up (p=0.02).
Conclusion: Substantial fibroblast activation was found in musculoskeletal system of psoriasis patients with arthralgias. This has been shown to correlate with tenderness localisation ad the clinical examination and with a high risk of transition to PsA. No correlations with MSUS findings were found. These results suggest that fibroblast activation depicted by 68Ga-FAPI-04-PET/CT imaging predate clinical and ultrasound changes of inflammation.
Figure 2 [Fig. 2]
References
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- Schmidkonz C, Atzinger A, Ramming A, Kuwert T. FAPI PET/CT Immune-Fibrosis Imaging for New Insights into Rheumatologic Disorders. J Nucl Med. 2023 Nov;64(11):1674-5. DOI: 10.2967/jnumed.123.266182
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- Luo Y, Pan Q, Zhou Z, Li M, Wei Y, Jiang X, Yang H, Li F. 68Ga-FAPI PET/CT for Rheumatoid Arthritis: A Prospective Study. Radiology. 2023 May;307(3):e222052. DOI: 10.1148/radiol.222052
