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

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.