Correlation Between 18F-FDG Uptake on PET and Molecular Biology in Metastatic Pulmonary Tumors

Abstract

(18)F-FDG PET can help in predicting therapeutic response and outcome in patients with metastatic pulmonary tumors. However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study was to investigate the underlying biologic mechanisms of (18)F-FDG uptake in metastatic pulmonary tumors. One hundred forty-six patients with metastatic pulmonary tumors who underwent (18)F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1), glucose transporter 3 (Glut3), hexokinase I, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and microvessel density determined by CD34. (18)F-FDG uptake and the expression of these biomarkers were correlated in primary lung cancer and benign pulmonary lesions. (18)F-FDG uptake in metastatic pulmonary tumors correlated significantly with the expression of Glut1 (γ = 0.4579, P < 0.0001), HIF-1α (γ = 0.3654, P < 0.0001), hexokinase I (γ = 0.3921, P < 0.0001), VEGF (γ = 0.5528, P < 0.0001), and CD34 (γ = 0.2342, P = 0.0044). (18)F-FDG uptake in metastatic pulmonary tumors was significantly lower than in primary lung cancer but higher than in benign pulmonary lesions. High uptake of (18)F-FDG was significantly associated with poor outcome after pulmonary metastasectomy. In patients with metastatic pulmonary tumors, (18)F-FDG uptake and the expression of Glut1, HIF-1α, and VEGF were significantly higher in adenocarcinoma and squamous cell carcinoma than in sarcoma. (18)F-FDG uptake was significantly correlated with tumor size (P < 0.0001), but there was no significant relationship between tumor size and the expression of these biomarkers. The amount of (18)F-FDG uptake in metastatic pulmonary tumors is determined by the presence of glucose metabolism (Glut1), phosphorylation of glucose (hexokinase I), hypoxia (HIF-1α), and angiogenesis (VEGF and microvessel density).