Abstract
327 Objectives Acute intravascular thrombosis is associated with focal increased uptake of FDG on PET and may provide a surrogate of early molecular events in the thrombotic cascade. Thrombi are rich in platelets, but also in neutrophils and monocytes. The objective was to characterize 2-deoxyglucose uptake by thrombotic activation of these cells. Methods Human neutrophils, platelets and monocytes were isolated and thrombotically activated by platelet activating factor (PAF), thrombin and lipopolysaccharide (LPS), respectively. The effect of activation on uptake of D-glucose analogs (fluorescent NBDG, 18F-FDG, 14C-2DG) was measured by gamma well counting, liquid scintillation counting, confocal microscopy, or flow cytometry. Activation-induced expression and localization of GLUT transporters and hexokinase (HK) was established by real-time PCR, or immunostaining with Western Blot analysis, confocal microscopy, or flow cytometry. Results PAF activation of neutrophils results in rapid 3-4 fold increase in uptake of D-glucose analogs, associated with increases in expression of GLUT-1, GLUT-3, GLUT-4, HK1, HK3, and small increases in GLUT-5 and 6. Thrombin activation of platelets results in a very rapid 3 fold increase in uptake of D-glucose analogs, and a 4-6 fold increase in membrane-associated GLUT-3 expression, likely by rapid externalization of an internal pool of transporter. LPS stimulation of monocytes produces only a minimal (10-30%) increase in glucose uptake, with a slight increase in GLUT-1 expression only. Conclusions Thrombogenic activation of platelets and neutrophils results in significant increased uptake of D-glucose analogs, associated with increased expression of GLUT-1, GLUT-3, GLUT-4, HK1, and HK 3, and externalization of an internal pool of GLUT-3 transporters by platelets. Stimulated monocytes show minimal increased uptake of D-glucose analogs. FDG PET may provide an imaging surrogate of early molecular events associated with thrombogenesis, and a mechanism for early assessment of antithrombotic therapies. Research Support NIH/NCI R01CA121003-01A
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