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 (18)F-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 (18)F-FDG and (18)F-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 (18)F-FDG was significantly increased at hypoxic conditions in two of the tumor and all endothelial cells, whereas (18)F-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 (18)F-FDG radiotracer uptake in tumors and for the visualization of tumors by means of PET.
Oswald
Joachim
J
Institute of Radiopharmacy, Research Center Dresden-Rossendorf, Dresden, Germany.
Treite
Franziska
F
Haase
Cathleen
C
Kampfrath
Thomas
T
Mäding
Peter
P
Schwenzer
Bernd
B
Bergmann
Ralf
R
Pietzsch
Jens
J
D015687:Cell Hypoxia; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008920:Misonidazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D005462:Fluorine Radioisotopes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole