Abstract 2197: Immune Modulation with Granulocyte/macrophage Colony-stimulating Factor Enhances PET Imaging of Inflamed Atherosclerotic Plaques
Objectives: PET imaging using FDG (a measure of tissue glycolysis) has been used to localize inflamed atherosclerotic plaques. The cytokine, granulocyte/macrophage colony-stimulating factor, (GMCSF), enhances expression of the glucose transporter molecule glut-1, and increases glycolysis in macrophages. Accordingly, we tested the hypothesis that GMCSF enhances FDG-PET detection of inflamed atherosclerotic lesions.
Methods: Atherosclerotic lesions were induced in 5 male New Zealand white rabbits via balloon injury of the aortoiliac arterial segment and exposure to a high cholesterol diet. Two rabbits fed standard chow served as controls. MicroPET FDG imaging (3 hrs after injection of 1 mCi/kg FDG) was performed twice for each animal: after injection of saline, and 2 days later, after administration of GMCSF (100 mcg SQ QDx2 and 100 mcg IV x 1). To facilitate localization of PET activity, CT angiography was performed on the animals. FDG uptake in the injured aortoiliac segments was measured by 2 observers who were blinded to treatment. A target-to background ratio (TBR) was calculated by dividing FDG uptake in the aortoiliac plaques (target) to FDG uptake in paraspinal muscles (background). Thereafter aortic plaque inflammation was assessed by analyzing plaque staining with RAM11.
Results: In control rabbits, mean (+/− SEM) FDG uptake (TBR) in aortoiliac segments was reduced after GMCSF (2.26+/− 0.07 vs. 1.46+/−0.17, P < 0.01). In contrast, within atherosclerotic rabbits, there was a 174% increase in TBR after GMCSF (5.8+/−0.14 vs. 10.1+/−0.40, P < 0.001). Moreover, FDG uptake (TBR) after GMCSF correlated with macrophage staining (R = 0.75, P < 0.01).
Conclusions: These data demonstrate that immune modulation with the cytokine GMCSF can be employed to enhance FDG localization of inflamed plaques in vivo. Further studies are needed to determine if immune modulation can be used to enhance the delivery of FDG and other imaging or therapeutic agents to inflamed plaques in humans.