2-deoxy-2-[18F]fluoro-d-mannose positron emission tomography imaging in atherosclerosis

PET imaging using 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) has been widely used for the detection of plaque inflammation. Here, however, Nobuhiro Tahara and colleagues explore the possibility of using 18 F-labeled mannose (2-deoxy-2-[ 18 F]fluoro-d-mannose, [ 18 F]FDM), a structural analog to FDG, as an alternative and potentially more specific PET tracer than FDG for assessing the risk of acute vascular events in patients. The approach targets the mannose receptor–bearing macrophages that are abundant in high-risk atherosclerotic plaques, with feasibility demonstrated in a rabbit model of atherosclerosis. Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2-[ 18 F]fluoro- D -glucose ([ 18 F]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because mannose is an isomer of glucose that is taken up by macrophages through glucose transporters and because mannose receptors are expressed on a subset of the macrophage population in high-risk plaques, we applied 18 F-labeled mannose (2-deoxy-2-[ 18 F]fluoro- D -mannose, [ 18 F]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [ 18 F]FDM and [ 18 F]FDG in atherosclerotic lesions in a rabbit model; [ 18 F]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[ 14 C]carbon- D -glucose ([ 14 C]2DG) support at least 35% higher [ 18 F]FDM uptake by macrophages in cell experiments. We also demonstrate that FDM restricts binding of anti–mannose receptor antibody to macrophages by approximately 35% and that mannose receptor targeting may provide an additional avenue for imaging of plaque inflammation.