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

Abstract

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.

• Authors: Nobuhiro Tahara, Jogeshwar Mukherjee, Hans J de Haas, Artiom D Petrov, Ahmed Tawakol, Nezam Haider, Atsuko Tahara, Cristian C Constantinescu, Jun Zhou, Hendrikus H Boersma, Tsutomu Imaizumi, Masataka Nakano, Aloke Finn, Zahi Fayad, Renu Virmani, Valentin Fuster, Lisardo Bosca, Jagat Narula
• Journal: Nature medicine (Nat Med) Vol. 20 Issue 2 Pg. 215-9 (Feb 2014) ISSN: 1546-170X [Electronic] United States
• PMID: 24412923 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Receptors, Cell Surface
• 2-deoxy-2-fluoromannose
• Rhamnose

Topics

• Analysis of Variance
• Animals
• Atherosclerosis (diagnosis, pathology)
• Autoradiography
• Humans
• Lectins, C-Type (immunology, metabolism)
• Macrophages (metabolism)
• Mannose Receptor
• Mannose-Binding Lectins (immunology, metabolism)
• Plaque, Atherosclerotic (ultrastructure)
• Positron-Emission Tomography (methods)
• Rabbits
• Receptors, Cell Surface (immunology, metabolism)
• Rhamnose (analogs & derivatives, pharmacokinetics)
• Tomography, X-Ray Computed