Assessing dynamic metabolic heterogeneity in non-small cell lung cancer patients via ultra-high sensitivity total-body [18F]FDG PET/CT imaging: quantitative analysis of [18F]FDG uptake in primary tumors and metastatic lymph nodes.

Purpose: This study aimed to quantitatively assess [¹⁸F]FDG uptake in primary tumor (PT) and metastatic lymph node (mLN) in newly diagnosed non-small cell lung cancer (NSCLC) using the total-body [¹⁸F]FDG PET/CT and to characterize the dynamic metabolic heterogeneity of NSCLC. Methods: The 60-min dynamic total-body [¹⁸F]FDG PET/CT was performed before treatment. The PTs and mLNs were manually delineated. An unsupervised K-means classification method was used to cluster patients based on the imaging features of PTs. The metabolic features, including Patlak-Ki, Patlak-Intercept, SUV_mean, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features, were extracted from PTs and mLNs. The targeted next-generation sequencing of tumor-associated genes was performed. The expression of Ki67, CD3, CD8, CD34, CD68, and CD163 in PTs was determined by immunohistochemistry. Results: A total of 30 patients with stage IIIA–IV NSCLC were enrolled. Patients were divided into fast dynamic FDG metabolic group (F-DFM) and slow dynamic FDG metabolic group (S-DFM) by the unsupervised K-means classification of PTs. The F-DFM group showed significantly higher Patlak-Ki (P < 0.001) and SUV_mean (P < 0.001) of PTs compared with the S-DFM group, while no significant difference was observed in Patlak-Ki and SUV_mean of mLNs between the two groups. The texture analysis indicated that PTs in the S-DFM group were more heterogeneous in FDG uptake than those in the F-DFM group. Higher T cells (CD3⁺/CD8⁺) and macrophages (CD68⁺/CD163⁺) infiltration in the PTs were observed in the F-DFM group. No significant difference was observed in tumor mutational burden between the two groups. Conclusion: The dynamic total-body [¹⁸F]FDG PET/CT stratified NSCLC patients into the F-DFM and S-DFM groups, based on Patlak-Ki and SUV_mean of PTs. PTs in the F-DFM group seemed to be more homogenous in terms of [¹⁸F]FDG uptake than those in the S-DFM group. The higher infiltrations of T cells and macrophages were observed in the F-DFM group, which suggested a potential benefit from immunotherapy. [ABSTRACT FROM AUTHOR]