BASIC SCIENCE INVESTIGATIONS Characterization of 18F-FDG Uptake in Human Endothelial Cells In Vitro

The contribution of 18F-FDG uptake by endothelial cells to uptake values measured by PET in various tissues is as yet unclear. We therefore sought to characterize 18F-FDG uptake in an in vitro model of human endothelial cells. Methods: Commercially obtained human umbilical vein endothelial cells (HUVECs) were seeded in 6-multiwell plates 48–96 h before incubation with 1–2 MBq 18F-FDG per well. Radioactivity measurements were performed after washing and mechanical dissolvation of the cellular monolayers. Cellular 18F-FDG uptake was referred to protein concentration. This experimental protocol was subsequently varied to study the effect of different parameters of interest. Furthermore, radio-thin-layer chromatography was used to identify intracellular 18F-FDG metabolites. 18F-FDG uptake in HUVECs was compared with that by a human monocyte–macrophage (HMM) preparation and by glioblastoma cells (GLIOs) under identical experimental conditions. Results: 18FFDG accumulated in HUVECs in a time-dependent manner and was trapped mainly as 18F-FDG-6-phosphate and 18F-FDG-1,6diphosphate. Unlabeled glucose and cytochalasin B competitively inhibited 18F-FDG uptake, whereas phlorizin had no significant effect. Glucose deprivation significantly enhanced 18F-FDG uptake by a factor of 2.7, whereas sodium depletion had no significant influence. HUVECs treated with vascular endothelial growth factor (VEGF) showed a significant 82% increase in 18F-FDG accumulation after a 2-h exposure to 50 ng/mL VEGF. 18F-FDG uptake in HUVECs was significantly higher than that in HMMs and in the range of the uptake values measured in GLIOs. Conclusion: 18F-FDG accumulates in HUVECs by mechanisms analogous to those in neoplastic cells or neurons. VEGF significantly stimulates endothelial 18F-FDG uptake. The observed differences in 18F-FDG uptake between HUVECs, HMMs, and GLIOs are difficult to extrapolate to in vivo conditions but stimulate further studies on the contribution of endothelial 18F-FDG uptake to the overall uptake of that tracer in neoplastic or vascular lesions.