Experimental hypoxia is a potent stimulus for radiotracer uptake in vitro: Comparison of different tumor cells and primary endothelial cells

Hypoxia causes upregulation of vascular endothelial growth factor (VEGF) which is a key regulator in tumor angiogenesis and essential for the proliferation of endothelial cells. Endothelial cells have been described to accumulate radiotracers like 18F-FDG. However, the contribution of radiotracer uptake by endothelial cells to uptake measured in tumors by positron emission tomography (PET) is still unclear. In this study 18F-FDG and 18F-FMISO radiotracer uptake in various tumor and primary endothelial cells cultured at hypoxic conditions was investigated. Experimental hypoxia was confirmed by significant upregulation of VEGF mRNA. In comparison to normoxic conditions, cellular uptake of 18F-FDG was significantly increased at hypoxic conditions in two of the tumor and all endothelial cells, whereas 18F-FMISO uptake was only enhanced in tumor cell lines HT-29 and MCF-7. Our data showed a marked influence of experimental hypoxia on the metabolism and gene expression of tumor and endothelial cells in vitro. This indicates an important contribution of endothelial cells to 18F-FDG radiotracer uptake in tumors and for the visualization of tumors by means of PET.