Preliminary clinical investigation of ¹⁸F-(2S,4R)-4-fluoroglutamine PET/CT in the evaluation of lung cancer.

Authors

Xiaoxia Xu, Futao Liu, Qing Xie, Song Liu, Nan Li, Zhi Yang

Published in

European journal of nuclear medicine and molecular imaging. Aug 06, 2026. Epub Aug 06, 2026.

Abstract

The clinical utility of ¹⁸F-fluoroglutamine (¹⁸F-FGln) PET/CT for characterizing metabolic heterogeneity and improving lung cancer staging remains underexplored.
In this prospective study, 31 patients with 36 primary lung lesions underwent dual-tracer (¹⁸F-FDG/¹⁸F-FGln) PET/CT. A metastatic cohort (n = 28) was analyzed for distant staging. Diagnostic performance was assessed using ROC analysis, logistic regression, and radiomic texture parameters (volume, mass, CT histogram features).
For primary lesions, ¹⁸F-FDG showed marginally higher detection rates (86.1% vs. 80.6%) and significantly greater avidity (SUVmax: 9.15 ± 0.16 (FDG) vs. 3.94 ± 1.57 (FGln), P < 0.001). CT texture analysis revealed kurtosis as an independent predictor of ¹⁸F-FGln uptake (OR = 1.16, P = 0.025), correlating with metabolic-structural coupling (r = 0.445, P = 0.009). In nodal staging, ¹⁸F-FGln identified improved diagnostic performance than ¹⁸F-FDG (AUC: 0.92 vs. 0.62). Metastatic lymph nodes showed higher ¹⁸F-FGln uptake, with increased SUVmax (3.57 ± 1.23 vs. 2.03 ± 0.47, P < 0.001) and TBR (2.11 ± 0.92 vs. 0.93 ± 0.21, P < 0.001). Multivariate analysis identified ¹⁸F-FGln SUVmax (OR = 32.79, P < 0.001) and CT density (OR = 0.90, P < 0.001) were predictors of metastatic lymph nodes (LNs). For distant metastases, ¹⁸F-FGln detected more distant lesions (86 vs. 70), particularly in bone (SUVmax 7.48 ± 3.03 vs. 6.80 ± 4.48) and brain (TBR 7.04 ± 2.96 vs. 0.88 ± 0.30, P < 0.001), altering staging in 3 cases.
¹⁸F-FGln PET/CT showed promising clinical potential in lung cancer, particularly in nodal staging, with higher diagnostic performance compared with ¹⁸F-FDG. It also demonstrated improved detection of bone and cerebral metastases in selected patients. Furthermore, ¹⁸F-FGln uptake correlated with CT-derived texture features, especially kurtosis, suggesting a possible association with tumor heterogeneity. Despite several false-negative cases, these results indicate that ¹⁸F-FGln may serve as a complementary metabolic imaging biomarker in lung cancer. Multicenter validation studies are needed to confirm these findings.
ChiCTR2000037834 Retrospectively Reg Date：2020-09-02.

PMID:
42560521
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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