Research article

Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation

Zhuangyu Zhang¹ , Josef Machac¹ , Gerard Helft² , Stephen G Worthley² , Cheuk Tang^3,4 , Azfar G Zaman² , Oswaldo J Rodriguez² , Monte S Buchsbaum³ , Valentin Fuster² and Juan J Badimon²

¹Division of Nuclear Medicine, Department of Radiology, The Mount Sinai School of Medicine, New York, NY, USA

²Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, NY, USA

³Neuroscience PET Laboratory, Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, USA

⁴Department of Radiology, The Mount Sinai School of Medicine, New York, NY, USA

author email corresponding author email

BMC Nuclear Medicine 2006, 6:3doi:10.1186/1471-2385-6-3

Published:	25 May 2006

Abstract

Background

Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of ¹⁸F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model.

Methods

Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta.

Results

Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity.

Conclusion

PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.