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.

中文翻译：

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通过超高灵敏度全身 [18F]FDG PET/CT 成像评估非小细胞肺癌患者的动态代谢异质性：原发性肿瘤和转移性淋巴结中 [18F]FDG 摄取的定量分析

目的

本研究旨在使用全身 [ ¹⁸ F]FDG PET/CT定量评估新诊断非小细胞肺癌 (NSCLC) 原发肿瘤 (PT) 和转移淋巴结 (mLN) 中的[ ¹⁸ F]FDG 摄取并表征 NSCLC 的动态代谢异质性。

方法

治疗前进行 60 分钟动态全身 [ ¹⁸ F]FDG PET/CT。PT 和 mLN 是手动描绘的。基于 PT 的成像特征，使用无监督 K 均值分类方法对患者进行聚类。从 PT 和 mLN 中提取代谢特征，包括 Patlak-Ki、Patlak-Intercept、SUV_{均值、代谢肿瘤体积 (MTV)、总病变糖酵解 (TLG) 和结构特征。}进行了肿瘤相关基因的靶向下一代测序。通过免疫组织化学测定 PT 中 Ki67、CD3、CD8、CD34、CD68 和 CD163 的表达。

结果

共有 30 名 IIIA-IV 期 NSCLC 患者入组。通过PT的无监督K均值分类将患者分为快动态FDG代谢组（F-DFM）和慢动态FDG代谢组（S-DFM）。与 S-DFM 组相比，F-DFM 组的 PT Patlak-Ki（ P  < 0.001）和 SUV_均值（P < 0.001）显着更高，而 Patlak-Ki 和 SUV_均值mLNs 之间 没有显着差异两组。纹理分析表明，与 F-DFM 组相比，S-DFM 组中的 PT 在 FDG 摄取方面更加异质。高等 T 细胞 (CD3 ⁺ /CD8 ⁺ ) 和巨噬细胞 (CD68 ⁺ /CD163 ⁺) 在 F-DFM 组中观察到 PT 的浸润。两组之间的肿瘤突变负荷未观察到显着差异。

结论

基于 PT 的 Patlak-Ki 和 SUV_平均值，动态全身 [ ¹⁸ F]FDG PET/CT 将 NSCLC 患者分层为 F-DFM 和 S-DFM 组。^{F-DFM 组中的 PT 在 [ 18} F]FDG 摄取方面似乎比 S-DFM 组中的更均匀。在 F-DFM 组中观察到更高的 T 细胞和巨噬细胞浸润，这表明免疫疗法具有潜在益处。