Hypoxia Imaging With 18F-Fluoroerythronitroimidazole Integrated PET/CT and Immunohistochemical Studies in Non-Small Cell Lung Cancer

Purpose: F-18-fluoroerythronitroimidazole (F-18-FETNIM) PET/CT allows a noninvasive assessment of tumor hypoxia. The purpose of this study was to evaluate a noninvasive and simplicity parameter for quantization of F-18-FETNIM uptake with expectations to predict survival in non-small cell lung cancer surgical patients and investigate the relationship between F-18-FETNIM uptake and molecular markers related to hypoxia, glucose metabolism, and angiogenesis. Patients and Methods: Thirty-two patients with biopsy-proven non-small cell lung cancer for surgical treatment were enrolled from March 2007 to February 2011. All patients had PET/CT studies with F-18-FETNIM and subsequently underwent surgery. Twenty-five patients had stage II disease of surgical staging only for statistical analysis. The tumor-to-mediastinum (T/Me) ratio was calculated and correlated with survival and immunohistochemical staining of hypoxia inducible factor 1 alpha (HIF-1 alpha), glucose transporter 1 (GLUT-1), and vascular endothelial growth factor (VEGF). Results: The actuarial survival was worse for patients showing a high T/Me ratio, the best discriminative cutoff value being 1.9. A statistically significant worse survival was noted in patients having a tumor with a T/Me ratio of 1.9 or greater, compared with patients showing a tumor with a T/Me ratio of less than 1.9, a 3-year survival of 43.8% and 88.9%, respectively (P = 0.034). There was a positive correlation between T/Me ratio and HIF-1 alpha (P = 0.023), GLUT-1 (P = 0.035), and VEGF (P = 0.042). Conclusions: T/Me ratio provides a noninvasive parameter for quantization of F-18-FETNIM uptake on PET/CT. T/Me ratio is correlated with a worse outcome and with the expression of HIF-1 alpha, GLUT-1, and VEGF, all up-regulated under hypoxic conditions.