Biological Significance of 18F-FDG Uptake on PET in Patients with Non-Small-Cell Lung Cancer
Menée sur 140 patients atteints d'un cancer du poumon non à petites cellules, cette étude analyse les mécanismes biologiques associés à l'absorption du fluorodésoxyglucose (18F) lors d'une tomographie numérique à émission de positrons et évalue la valeur pronostique de cette absorption
Background : The aim of this study is to investigate the underlying biologic mechanisms of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) uptake on positron emission tomography (PET) in non-small cell lung cancer (NSCLC).
Methods : One-hundred forty patients with NSCLC who underwent 18F-FDG PET were included in the study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), GLUT3, hypoxia-inducible factor-1 alpha (HIF-1
α), hexokinase I, vascular endothelial growth factor (VEGF), microvessels (CD34), epidermal growth factor receptor (EGFR), and molecules relevant to PI3 K/Akt/mTOR signaling pathway (PTEN, p-Akt, p-mTOR and p-S6). We also conducted in vitro studies of 18F-FDG uptake and mTOR inhibition in NSCLC cells.
Results
:
High 18F-FDG uptake was significantly associated with poor prognosis in NSCLC patients. 18F-FDG uptake was significantly correlated with GLUT1, hexokinase I, HIF-1α, VEGF, CD34, p-Akt, p-mTOR and EGFR. PTEN expression showed inverse correlation with 18F-FDG uptake. In in vitro study, 18F-FDG uptake was markedly decreased by the inhibition of GLUT1 and GLUT1 upregulation by the induction of HIF-1α increased the 18F-FDG uptake. Inhibition of both mTOR complex1 (mTORC1) and mTORC2 suppressed cell growth, but activity of mTORC1 regulated the 18F-FDG uptake. NCI-H1650 cells with PTEN loss showed the highest 18F-FDG uptake and the least sensitivity to mTOR inhibitors.
Conclusion
:
The amount of 18F-FDG accumulation is associated with molecules relevant to glucose metabolism, hypoxia, angiogenesis and mTOR signaling pathway. Especially, PTEN status may affect not only 18F-FDG uptake but also effect of mTOR inhibitors on the growth of NSCLC.
Lung Cancer , résumé, 2012