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. 2025 Feb;16(1):e13730.
doi: 10.1002/jcsm.13730.

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

Minseok Suh  1 , Joonhyung Gil  1 , Yeon-Koo Kang  1 , Hongyoon Choi  1 , Gi Jeong Cheon  1
Affiliations

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

Minseok Suh et al. J Cachexia Sarcopenia Muscle. 2025 Feb.

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.

Keywords: FAP; FAPI PET; ageing; muscle density; skeletal muscle.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(a) Correlation between skeletal muscle SUVmean and age. (b) Correlation between SUVmean and average CT Hounsfield unit of the skeletal muscle.
FIGURE 2
FIGURE 2
Fibroblast activation protein expression across different age groups. A box and whisker plot was generated through median, quartiles, interquartile range, and potential outliers.
FIGURE 3
FIGURE 3
Representative image of age‐related increase in FAPI uptake in skeletal muscle.
See this image and copyright information in PMC

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