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First published online May 14, 2009, 10.2967/jnumed.108.060749
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Journal of Nuclear Medicine Vol. 50 No. 6 959-965
© 2009 by Society of Nuclear Medicine
doi: 10.2967/jnumed.108.060749

Basic Science Investigation

Quantification of Inflammation Within Rabbit Atherosclerotic Plaques Using the Macrophage-Specific CT Contrast Agent N1177: A Comparison with 18F-FDG PET/CT and Histology

Fabien Hyafil1,2, Jean-Christophe Cornily1,3, James H.F. Rudd1,4, Josef Machac5, Laurent J. Feldman2 and Zahi A. Fayad1

1 Translational and Molecular Imaging Institute and Imaging Science Laboratories, Mount Sinai School of Medicine, New York, New York; 2 Department of Cardiology and Nuclear Medicine, Bichat Hospital, Assistance Publique-Hôpitaux de Paris and Institut National de la Santé et de la Recherche Médicale, 698, Paris, France; 3 Department of Cardiology, Brest University Hospital, Brest, France, and ORPHY Laboratory, Université de Brest, Brest, France; 4 Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom; and 5 Department of Nuclear Medicine, Mount Sinai Hospital, New York, New York

Correspondence: For correspondence or reprints contact: Zahi A. Fayad, Mount Sinai School of Medicine, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, Box 1234, New York, NY 10029. E-mail: zahi.fayad{at}mssm.edu

Macrophages play a key role in atherosclerotic plaque rupture. The iodine-based contrast agent N1177 accumulates in macrophages, allowing for their detection with CT. In this study, we tested whether the intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlated with inflammatory activity evaluated with 18F-FDG PET/CT and macrophage density on histology. Methods: Atherosclerotic plaques were induced in the aorta of New Zealand White rabbits (n = 7) by a repeated balloon injury (4 wk apart) and 4 mo of hyperlipemic diet. Noninjured rabbits, fed a chow diet, were used as controls (n = 3). A CT scan of the aorta (n = 10) was acquired in each rabbit before, during, and at 2 h after intravenous injection of N1177 (250 mg of iodine/kg). One week later, the same rabbits underwent PET/CT 3 h after injection of 18F-FDG (37 MBq/kg [1 mCi/kg]). CT enhancement was calculated as the difference in aortic wall densities between images obtained before and images obtained at 2 h after injection of N1177. Mean standardized uptake values were measured on PET axial slices of the aorta in regions of interest encompassing the vessel wall. Macrophage density was measured by immunohistology (anti-RAM-11 antibody) on corresponding aortic cross-sections. Results: N1177-enhanced CT measured stronger enhancement in the aortic wall of atherosclerotic rabbits than in control rabbits (10.0 ± 5.2 vs. 2.0 ± 2.1 Hounsfield units, respectively; P < 0.05). After the injection of 18F-FDG, PET detected higher standardized uptake values in the aortic wall of atherosclerotic rabbits than in control rabbits (0.61 ± 0.12 vs. 0.21 ± 0.02; P < 0.05). The intensity of enhancement in the aortic wall measured with CT after injection of N1177 correlated with 18F-FDG uptake on PET/CT (r = 0.61, P < 0.001) and macrophage density on immunohistology (r = 0.63, P < 0.001). Conclusion: The intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlates with intense uptake of 18F-FDG measured with PET and with macrophage density on histology, suggesting a role for N1177 in noninvasive identification of high-risk atherosclerotic plaques with CT.

Key Words: atherosclerosis • computed tomography • contrast agents • macrophages • positron emission tomography

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.


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