Biologic Correlation of 2-[18F]-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission Tomography in Thymic Epithelial Tumors

Purpose The usefulness of 2-[F-18]-fluoro-2-deoxy-D-glucose ([F-18]FDG) positron emission tomography (PET) can help predict the grade of malignancy and staging in thymic epithelial tumors. However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study was to investigate the underlying biologic mechanisms of [F-18] FDG uptake. Patients and Methods Forty-nine patients with thymic epithelial tumors who underwent [18F] FDG PET were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), microvessels (CD31 and CD34), cell cycle control marker (p53), and apoptosis marker (bcl-2). We also conducted an in vitro study of [F-18] FDG uptake in a thymic tumor cell line. Results There was a positive correlation between [F-18] FDG uptake and GLUT1 (P < .0001), HIF-1 alpha (P = .0036), VEGF (P <= .0001), microvessel density (MVD; P < .0001), and p53 (P = .0002). GLUT3 and bcl-2 showed no positive correlation with [18F] FDG uptake. The expression of Glut1, HIF-1 alpha, VEGF, CD31, CD34, and p53 was also significantly associated with the grade of malignancy and poor outcome in thymic epithelial tumors, whereas this relationship was not observed in GLUT3 and bcl-2. Our in vitro study demonstrated that upregulation of GLUT1 and HIF-1 alpha was closely associated with [F-18] FDG uptake into thymic tumor cell. Conclusion [F-18] FDG uptake in thymic epithelial tumors is determined by the presence of glucose metabolism (GLUT1), hypoxia (HIF-1 alpha)angiogenesis (VEGF and MVD), and cell cycle regulator (p53). J Clin Oncol 28: 3746-3753. (C) 2010 by American Society of Clinical Oncology