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

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

doi:10.1038/nm.3437

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

159 Citations (Scopus)

Abstract

Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]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 F-18-labeled mannose (2-deoxy-2[F-18]fluoro-D-mannose, [F-18]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [F-18]FDM and [F-18]FDG in atherosclerotic lesions in a rabbit model; [F-18]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[C-14]carbon-D-glucose ([C-14]2DG) support at least 35% higher [F-18]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.

Original language	English
Pages (from-to)	215-219
Number of pages	5
Journal	Nature Medicine
Volume	20
Issue number	2
DOIs	https://doi.org/10.1038/nm.3437
Publication status	Published - Feb-2014

Keywords

NONINVASIVE DETECTION
GLUCOSE TRANSPORTERS
ADHESION MOLECULE-1
PLAQUE INFLAMMATION
VULNERABLE PLAQUES
DISEASE
FLUORODEOXYGLUCOSE
MACROPHAGES
MECHANISMS

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Tahara, N., Mukherjee, J., de Haas, H. J., Petrov, A. D., Tawakol, A., Haider, N., Tahara, A., Constantinescu, C. C., Zhou, J., Boersma, H. H., Imaizumi, T., Nakano, M., Finn, A., Fayad, Z., Virmani, R., Fuster, V., Bosca, L., & Narula, J. (2014). 2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis. Nature Medicine, 20(2), 215-219. https://doi.org/10.1038/nm.3437

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title = "2-deoxy-2[F-18]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[F-18]fluoro-D-glucose ([F-18]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 F-18-labeled mannose (2-deoxy-2[F-18]fluoro-D-mannose, [F-18]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [F-18]FDM and [F-18]FDG in atherosclerotic lesions in a rabbit model; [F-18]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[C-14]carbon-D-glucose ([C-14]2DG) support at least 35% higher [F-18]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.",

keywords = "NONINVASIVE DETECTION, GLUCOSE TRANSPORTERS, ADHESION MOLECULE-1, PLAQUE INFLAMMATION, VULNERABLE PLAQUES, DISEASE, FLUORODEOXYGLUCOSE, MACROPHAGES, MECHANISMS",

author = "Nobuhiro Tahara and Jogeshwar Mukherjee and {de Haas}, {Hans J} and Petrov, {Artiom D} and Ahmed Tawakol and Nezam Haider and Atsuko Tahara and Constantinescu, {Cristian C} and Jun Zhou and Boersma, {Hendrikus H} and Tsutomu Imaizumi and Masataka Nakano and Aloke Finn and Zahi Fayad and Renu Virmani and Valentin Fuster and Lisardo Bosca and Jagat Narula",

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doi = "10.1038/nm.3437",

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Tahara, N, Mukherjee, J, de Haas, HJ, Petrov, AD, Tawakol, A, Haider, N, Tahara, A, Constantinescu, CC, Zhou, J, Boersma, HH, Imaizumi, T, Nakano, M, Finn, A, Fayad, Z, Virmani, R, Fuster, V, Bosca, L & Narula, J 2014, '2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis', Nature Medicine, vol. 20, no. 2, pp. 215-219. https://doi.org/10.1038/nm.3437

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T1 - 2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis

AU - Tahara, Nobuhiro

AU - Mukherjee, Jogeshwar

AU - de Haas, Hans J

AU - Petrov, Artiom D

AU - Tawakol, Ahmed

AU - Haider, Nezam

AU - Tahara, Atsuko

AU - Constantinescu, Cristian C

AU - Zhou, Jun

AU - Boersma, Hendrikus H

AU - Imaizumi, Tsutomu

AU - Nakano, Masataka

AU - Finn, Aloke

AU - Fayad, Zahi

AU - Virmani, Renu

AU - Fuster, Valentin

AU - Bosca, Lisardo

AU - Narula, Jagat

PY - 2014/2

Y1 - 2014/2

N2 - Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]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 F-18-labeled mannose (2-deoxy-2[F-18]fluoro-D-mannose, [F-18]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [F-18]FDM and [F-18]FDG in atherosclerotic lesions in a rabbit model; [F-18]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[C-14]carbon-D-glucose ([C-14]2DG) support at least 35% higher [F-18]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.

AB - Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]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 F-18-labeled mannose (2-deoxy-2[F-18]fluoro-D-mannose, [F-18]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [F-18]FDM and [F-18]FDG in atherosclerotic lesions in a rabbit model; [F-18]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[C-14]carbon-D-glucose ([C-14]2DG) support at least 35% higher [F-18]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.

KW - NONINVASIVE DETECTION

KW - GLUCOSE TRANSPORTERS

KW - ADHESION MOLECULE-1

KW - PLAQUE INFLAMMATION

KW - VULNERABLE PLAQUES

KW - DISEASE

KW - FLUORODEOXYGLUCOSE

KW - MACROPHAGES

KW - MECHANISMS

U2 - 10.1038/nm.3437

DO - 10.1038/nm.3437

M3 - Article

C2 - 24412923

SN - 1078-8956

VL - 20

SP - 215

EP - 219

JO - Nature Medicine

JF - Nature Medicine

IS - 2

ER -

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

Abstract

Keywords

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