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Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography

Abstract

Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.

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Figure 1: Properties of the contrast agent N1177.
Figure 2: Kinetics and distribution of N1177 in nonatherosclerotic rabbits.
Figure 3: Imaging of macrophages in atherosclerotic plaques.
Figure 4: Histology.

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Acknowledgements

We thank G. Cornily for her assistance with statistical analysis. This work was supported by grants from the Fédération Française de Cardiologie (F.H. and J.-C.C.) and from the US National Institutes of Health/National Heart, Lung and Blood Institute (R01 HL71021 and R01 HL78667 to Z.A.F.).

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Authors and Affiliations

Authors

Contributions

F.H. and Z.A.F. conceived of and designed the project. F.H. and J.-C.C. performed the CT scans and the data analysis. J.E.F. performed the cell culture experiments. R.G. conducted the electron microscopy studies. E.V. performed the immunohistology studies. F.H., J.-C.C.,V.A., E.A.F., V.F., L.J.F. and Z.A.F. contributed to the writing of the manuscript. All authors discussed and commented on the manuscript.

Corresponding author

Correspondence to Zahi A Fayad.

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The authors declare no competing financial interests.

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Hyafil, F., Cornily, JC., Feig, J. et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat Med 13, 636–641 (2007). https://doi.org/10.1038/nm1571

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