Relationship between 18F-FDG uptake on positron emission tomography and molecular biology in malignant pleural mesothelioma

The usefulness of 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron emission tomography (PET) can help for predicting the therapeutic response and outcome in malignant pleural mesothelioma (MPM). However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study is to investigate the underlying biologic mechanisms of (18)F-FDG uptake.

Twenty-one patients with MPM who underwent (18)F-FDG PET before treatment were included in this study. Tumour sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); cell proliferation (Ki-67 labelling index); Akt/mTOR signalling pathway (PTEN, p-Akt, p-mTOR and p-S6K); cell cycle control (p53 and pRb); apoptosis marker (bcl-2). We also conducted an in vitro study of (18)F-FDG uptake in mesothelioma cell lines.

(18)F-FDG uptake was significantly correlated with Glut1 (p<0.0001), HIF-1α (p=0.006), hexokinase I (p=0.0002), VEGF (p=0.0013), CD34 (p=0.0001), Ki-67(p=0.0047), mTOR (p=0.00478) and p53 (p=0.0004). High uptake of (18)F-FDG was significantly associated with poor outcome in MPM. Our in vitro study showed that upregulation of Glut1 and HIF-1α was closely related with (18)F-FDG uptake into mesothelioma cell, and mTOR inhibitor induced a decrease in Glut1 expression and (18)F-FDG uptake.

The amount of (18)F-FDG uptake in MPM is determined by the presence of glucose metabolism, phosphorylation of glucose, hypoxia, angiogenesis, cell proliferation (Ki-67), cell cycle regulator, and mTOR signalling pathway.