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

B. van Leer; M. Londema; COVID-CLIMATE consortium; Kasalak; J. H. van Snick; M. L. Duiverman; J. C. Kuijvenhoven; M. D. de Kruif; D. E. Oprea-Lager; K. Pabst; M. E. Hellemons; H. H. Boersma; M. Prokop; M. W. Nijsten; A. W.J.M. Glaudemans; J. Pillay; R. H.J.A. Slart

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^*
, M. Londema
, COVID-CLIMATE consortium
, Kasalak
, J. H. van Snick
, M. L. Duiverman
, J. C. Kuijvenhoven
, M. D. de Kruif
, D. E. Oprea-Lager
, K. Pabst
, M. E. Hellemons
, H. H. Boersma
, M. Prokop
, M. W. Nijsten
, A. W.J.M. Glaudemans
, J. Pillay
, R. H.J.A. Slart

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	565-573
Number of pages	9
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	53
Issue number	1
DOIs	https://doi.org/10.1007/s00259-025-07376-y
Publication status	Published - Dec 2025

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Publisher Copyright:
© The Author(s) 2025.

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van Leer, B., Londema, M., COVID-CLIMATE consortium, Kasalak, van Snick, J. H., Duiverman, M. L., Kuijvenhoven, J. C., de Kruif, M. D., Oprea-Lager, D. E., Pabst, K., Hellemons, M. E., Boersma, H. H., Prokop, M., Nijsten, M. W., Glaudemans, A. W. J. M., Pillay, J., & Slart, R. H. J. A. (2025). [⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge. European Journal of Nuclear Medicine and Molecular Imaging, 53(1), 565-573. https://doi.org/10.1007/s00259-025-07376-y

@article{a629822cb74f48a587d1810a248fa229,

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

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.",

author = "\{van Leer\}, B. and M. Londema and \{COVID-CLIMATE consortium\} and Kasalak and \{van Snick\}, \{J. H.\} and Duiverman, \{M. L.\} and Kuijvenhoven, \{J. C.\} and \{de Kruif\}, \{M. D.\} and Oprea-Lager, \{D. E.\} and K. Pabst and Hellemons, \{M. E.\} and Boersma, \{H. H.\} and M. Prokop and Nijsten, \{M. W.\} and Glaudemans, \{A. W.J.M.\} and J. Pillay and Slart, \{R. H.J.A.\} and A. Schols and Gietema, \{H. A.\} and \{Mohamed Hoesein\}, \{F. A.A.\} and Postma, \{D. F.\} and Lammertsma, \{A. A.\} and Beenen, \{L. F.M.\} and St{\"o}ger, \{J. L.\} and Bek, \{L. M.\} and \{van den Borst\}, B. and S. Schalekamp and D. Gach and \{van Kuijk\}, \{S. M.J.\} and Beijers, \{R. J.H.C.G.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1007/s00259-025-07376-y",

language = "English",

volume = "53",

pages = "565--573",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

number = "1",

}

van Leer, B, Londema, M, COVID-CLIMATE consortium, Kasalak, van Snick, JH, Duiverman, ML, Kuijvenhoven, JC, de Kruif, MD, Oprea-Lager, DE, Pabst, K, Hellemons, ME , Boersma, HH, Prokop, M, Nijsten, MW, Glaudemans, AWJM, Pillay, J & Slart, RHJA 2025, '[⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge', European Journal of Nuclear Medicine and Molecular Imaging, vol. 53, no. 1, pp. 565-573. https://doi.org/10.1007/s00259-025-07376-y

[⁶⁸Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge. / van Leer, B.; Londema, M.; COVID-CLIMATE consortium et al.
In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 53, No. 1, 12.2025, p. 565-573.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - [68Ga]FAPI PET/CT reveals increased pulmonary fibroblast activation protein expression in long COVID patients after ICU discharge

AU - van Leer, B.

AU - Londema, M.

AU - COVID-CLIMATE consortium

AU - Kasalak,

AU - van Snick, J. H.

AU - Duiverman, M. L.

AU - Kuijvenhoven, J. C.

AU - de Kruif, M. D.

AU - Oprea-Lager, D. E.

AU - Pabst, K.

AU - Hellemons, M. E.

AU - Boersma, H. H.

AU - Prokop, M.

AU - Nijsten, M. W.

AU - Glaudemans, A. W.J.M.

AU - Pillay, J.

AU - Slart, R. H.J.A.

AU - Schols, A.

AU - Gietema, H. A.

AU - Mohamed Hoesein, F. A.A.

AU - Postma, D. F.

AU - Lammertsma, A. A.

AU - Beenen, L. F.M.

AU - Stöger, J. L.

AU - Bek, L. M.

AU - van den Borst, B.

AU - Schalekamp, S.

AU - Gach, D.

AU - van Kuijk, S. M.J.

AU - Beijers, R. J.H.C.G.

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105008561918

U2 - 10.1007/s00259-025-07376-y

DO - 10.1007/s00259-025-07376-y

M3 - Article

C2 - 40542858

AN - SCOPUS:105008561918

SN - 1619-7070

VL - 53

SP - 565

EP - 573

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 1

ER -

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

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