. 2025 Jun 21.

doi: 10.1007/s00259-025-07376-y. Online ahead of print.

[⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge

B van Leer^{1

2}, M Londema³, Ö Kasalak⁴, J H van Snick⁵, M L Duiverman⁶, J C Kuijvenhoven⁷, M D de Kruif⁸, D E Oprea-Lager^{9

10}, K Pabst¹¹, M E Hellemons¹², H H Boersma^{5

13}, M Prokop^{4

14}, M W Nijsten³, A W J M Glaudemans⁵, J Pillay^#^{3

15}, R H J A Slart^#^{5

16}; COVID-CLIMATE consortium

Collaborators, Affiliations

Collaborators

COVID-CLIMATE consortium:
R J H C G Beijers, S M J van Kuijk, D Gach, S Schalekamp, B van den Borst, L M Bek, J L Stöger, L F M Beenen, A A Lammertsma, D F Postma, F A A Mohamed Hoesein, H A Gietema, A Schols

Affiliations

¹ Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. b.van.leer@umcg.nl.
² Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, TA29, PO box: 30001, Groningen, The Netherlands. b.van.leer@umcg.nl.
³ Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, TA29, PO box: 30001, Groningen, The Netherlands.
⁶ Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ Department of Pulmonology, Medical Center Leeuwarden, Leeuwarden, The Netherlands.
⁸ Department of Pulmonology, Zuyderland Medical Center, Heerlen, The Netherlands.
⁹ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
¹⁰ Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands.
¹¹ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Essen, Essen, Germany.
¹² Department of Pulmonology, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, The Netherlands.
¹³ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁴ Department of Radiology, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands.
¹⁵ Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
¹⁶ Biomedical Photonic Imaging Group, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.

^# Contributed equally.

PMID: 40542858
DOI: 10.1007/s00259-025-07376-y

[⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge

B van Leer et al. Eur J Nucl Med Mol Imaging. 2025.

. 2025 Jun 21.

doi: 10.1007/s00259-025-07376-y. Online ahead of print.

Authors

Collaborators

COVID-CLIMATE consortium:
R J H C G Beijers, S M J van Kuijk, D Gach, S Schalekamp, B van den Borst, L M Bek, J L Stöger, L F M Beenen, A A Lammertsma, D F Postma, F A A Mohamed Hoesein, H A Gietema, A Schols

Affiliations

¹ Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. b.van.leer@umcg.nl.
² Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, TA29, PO box: 30001, Groningen, The Netherlands. b.van.leer@umcg.nl.
³ Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, TA29, PO box: 30001, Groningen, The Netherlands.
⁶ Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ Department of Pulmonology, Medical Center Leeuwarden, Leeuwarden, The Netherlands.
⁸ Department of Pulmonology, Zuyderland Medical Center, Heerlen, The Netherlands.
⁹ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
¹⁰ Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands.
¹¹ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Essen, Essen, Germany.
¹² Department of Pulmonology, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, The Netherlands.
¹³ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁴ Department of Radiology, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands.
¹⁵ Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
¹⁶ Biomedical Photonic Imaging Group, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.

^# Contributed equally.

PMID: 40542858
DOI: 10.1007/s00259-025-07376-y

Abstract

Purpose: Post-acute sequelae of COVID-19 (PASC) has emerged as a major healthcare problem. A comprehensive mechanism of disease remains to be elucidated. In this study we aimed to explore pulmonary and muscle fibroblast activation protein (FAP) activity in former critical COVID-19 patients with persistent dyspnea, using [⁶⁸Ga]FAPI-46 PET/CT.

Methods: In this single center prospective observational study we included former critical COVID-19 patients reporting complaints of dyspnea > 3 months after hospital discharge. A [⁶⁸Ga]FAPI PET/CT scan was performed including a high-resolution CT scan, lung function test, EQ-5D questionnaire, 6 min walking test and inflammatory markers. Age and sex-matched subjects, without pulmonary pathology, served as controls. The [⁶⁸Ga]FAPI uptake was corrected for lean body mass and the target-to-background ratio (TBR) was calculated.

Results: Eighteen PASC patients and 15 controls (median age 59 and 63 years and BMI of 34.6 and 25.2 kg/m²) were included. The interval between hospital discharge and study visit was 30 months. Increased pulmonary FAP expression was observed in PASC, (TBR 0.79 ± 0.23) compared to controls (TBR 0.40 ± 0.13, P < 0.001). Increased FAP expression was also observed in the paravertebral muscles (PASC: TBR 1.17 and controls TBR 1.00, P = 0.03). Forced expiratory volume and forced vital capacity showed moderate negative correlation with the pulmonary TBR, while the percentage of ground glass opacities showed a moderate positive correlation.

Conclusion: [⁶⁸Ga]FAPI PET/CT demonstrated elevated FAP expression in PASC. These findings provide insight into possible pathophysiological mechanisms of PASC and a potential new diagnostic modality.

Keywords: Critically ill; FAPI PET/CT; Long COVID; Muscles; Post-acute sequalae of COVID-19; Respiratory.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: The study protocol was approved by the Institution Review Board of the University Medical Center Groningen (202100802) and registered at ClinicalTrials.gov (NCT05981885). The study was performed in accordance with the Declaration of Helsinki. All patients provided written informed consent. Competing interests: Janesh Pillay is supported by a research grant from the Netherlands Organization for Health Research and Development, The Netherlands (ZonMw Clinical Fellowship grant 09032212110044) and has received funding from ‘a Partnership of Siemens and UMCG for building the future of Health’ (PUSH MO24.00027). The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Riemer Slart is an associate editor for EJNMMI. Information regarding FAPI-46 precursor composition used in this study containing approximately 20% of the non-binding (R)-enantiomer was provided by GE HealthCare and incorporated in this manuscript.

References

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[⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge

Collaborators

Affiliations

[⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous