Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging

ABSTRACT Background Fibroblast activation protein (FAP) is prominently involved in the tumour microenvironment and tissue remodelling processes in most cancers, and its expression is also noted in normal skeletal muscle. This study aims to explore the relationship between FAP expression and age‐rela...

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Main Authors: Minseok Suh, Joonhyung Gil, Yeon‐Koo Kang, Hongyoon Choi, Gi Jeong Cheon
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Journal of Cachexia, Sarcopenia and Muscle
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Online Access:https://doi.org/10.1002/jcsm.13730
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author Minseok Suh
Joonhyung Gil
Yeon‐Koo Kang
Hongyoon Choi
Gi Jeong Cheon
author_facet Minseok Suh
Joonhyung Gil
Yeon‐Koo Kang
Hongyoon Choi
Gi Jeong Cheon
author_sort Minseok Suh
collection DOAJ
description ABSTRACT Background Fibroblast activation protein (FAP) is prominently involved in the tumour microenvironment and tissue remodelling processes in most cancers, and its expression is also noted in normal skeletal muscle. This study aims to explore the relationship between FAP expression and age‐related muscle characteristics through FAP inhibitor (FAPI) PET/CT imaging. Methods This retrospective analysis studied 54 patients with lung cancer (n = 27) and pancreatic cancer (n = 27) using FAPI PET/CT. Imaging‐based muscle features including the mean standardised uptake value (SUVmean), skeletal muscle index (SMI) and Hounsfield units (HU) were evaluated. Age‐related FAP expression in skeletal muscles was also evaluated using the Genotype‐Tissue Expression (GTEx) dataset. Statistical analyses included Spearman's rank correlation and Kruskal–Wallis test, with a p‐value of less than 0.05 considered significant. Results Analysis revealed a moderate to strong positive correlation between FAPI SUVmean and age (ρ = 0.368, p = 0.006), with older age groups showing higher muscle uptake. Within specific cohorts, the FAPI‐74 group demonstrated a stronger correlation (ρ = 0.500, p = 0.008) compared to the FAPI‐46 group (ρ = 0.319, p = 0.105). SUVmean also correlated negatively with muscle density (HU) (ρ = −0.298, p = 0.029), suggesting an association with higher fat infiltration. GTEx data supported these findings, showing a significant increase in FAP expression across age groups (p < 0.001), with the highest median FAP in the 70–79 age group. Conclusions This study demonstrates an age‐related increase in FAPI uptake in skeletal muscle, correlated with changes in muscle density and fat infiltration. The role of FAP extends beyond pathology to normal muscle, indicating broader biological functions. Accordingly, FAPI PET shows promise for assessing age‐related muscle health and quality.
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spelling doaj-art-e17aabee97cc414a89a8d5477eaf75792025-08-20T02:06:23ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-02-01161n/an/a10.1002/jcsm.13730Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET ImagingMinseok Suh0Joonhyung Gil1Yeon‐Koo Kang2Hongyoon Choi3Gi Jeong Cheon4Departments of Nuclear Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartments of Nuclear Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartments of Nuclear Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartments of Nuclear Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaDepartments of Nuclear Medicine, Seoul National University Hospital Seoul National University College of Medicine Seoul South KoreaABSTRACT Background Fibroblast activation protein (FAP) is prominently involved in the tumour microenvironment and tissue remodelling processes in most cancers, and its expression is also noted in normal skeletal muscle. This study aims to explore the relationship between FAP expression and age‐related muscle characteristics through FAP inhibitor (FAPI) PET/CT imaging. Methods This retrospective analysis studied 54 patients with lung cancer (n = 27) and pancreatic cancer (n = 27) using FAPI PET/CT. Imaging‐based muscle features including the mean standardised uptake value (SUVmean), skeletal muscle index (SMI) and Hounsfield units (HU) were evaluated. Age‐related FAP expression in skeletal muscles was also evaluated using the Genotype‐Tissue Expression (GTEx) dataset. Statistical analyses included Spearman's rank correlation and Kruskal–Wallis test, with a p‐value of less than 0.05 considered significant. Results Analysis revealed a moderate to strong positive correlation between FAPI SUVmean and age (ρ = 0.368, p = 0.006), with older age groups showing higher muscle uptake. Within specific cohorts, the FAPI‐74 group demonstrated a stronger correlation (ρ = 0.500, p = 0.008) compared to the FAPI‐46 group (ρ = 0.319, p = 0.105). SUVmean also correlated negatively with muscle density (HU) (ρ = −0.298, p = 0.029), suggesting an association with higher fat infiltration. GTEx data supported these findings, showing a significant increase in FAP expression across age groups (p < 0.001), with the highest median FAP in the 70–79 age group. Conclusions This study demonstrates an age‐related increase in FAPI uptake in skeletal muscle, correlated with changes in muscle density and fat infiltration. The role of FAP extends beyond pathology to normal muscle, indicating broader biological functions. Accordingly, FAPI PET shows promise for assessing age‐related muscle health and quality.https://doi.org/10.1002/jcsm.13730ageingFAPFAPI PETmuscle densityskeletal muscle
spellingShingle Minseok Suh
Joonhyung Gil
Yeon‐Koo Kang
Hongyoon Choi
Gi Jeong Cheon
Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging
Journal of Cachexia, Sarcopenia and Muscle
ageing
FAP
FAPI PET
muscle density
skeletal muscle
title Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging
title_full Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging
title_fullStr Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging
title_full_unstemmed Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging
title_short Aged‐Related Fibroblast Activation Protein Expression in Skeletal Muscles Evaluated by PET Imaging
title_sort aged related fibroblast activation protein expression in skeletal muscles evaluated by pet imaging
topic ageing
FAP
FAPI PET
muscle density
skeletal muscle
url https://doi.org/10.1002/jcsm.13730
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AT yeonkookang agedrelatedfibroblastactivationproteinexpressioninskeletalmusclesevaluatedbypetimaging
AT hongyoonchoi agedrelatedfibroblastactivationproteinexpressioninskeletalmusclesevaluatedbypetimaging
AT gijeongcheon agedrelatedfibroblastactivationproteinexpressioninskeletalmusclesevaluatedbypetimaging