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Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Fluorine 18 fluorodeoxyglucose (FDG) has been shown to accumulate in inflamed tissues. However, it is not known whether vascular inflammation can be measured noninvasively. The aim of this study was to test the hypothesis that vascular inflammation can be measured noninvasively by use of positron emission tomography (PET) with FDG.

Methods and Results

Inflamed atherosclerotic lesions were induced in 9 male New Zealand white rabbits via balloon injury of the aortoiliac arterial segment and exposure to a high cholesterol diet. Ten rabbits fed standard chow served as controls. Three to six months after balloon injury, the rabbits were injected with FDG (1 mCi/kg), after which aortic uptake of FDG was assessed (3 hours after injection). Biodistribution of FDG activity within aortic segments was obtained by use of standard well gamma counting. FDG uptake was also determined noninvasively in a subset of 6 live atherosclerotic rabbits and 5 normal rabbits, via PET imaging and measurement of standardized uptake values over the abdominal aorta. Plaque macrophage density and smooth muscle cell density were determined by planimetric analysis of RAM-11 and smooth muscle actin staining, respectively. Biodistribution of FDG within nontarget organs was similar between atherosclerotic and control rabbits. However, well counter measurements of FDG uptake were significantly higher within atherosclerotic aortas compared with control aortas (P <.001). Within the upper abdominal aorta of the atherosclerotic group (area of greatest plaque formation), there was an approximately 19-fold increase in FDG uptake compared with controls (108.9 ± 55.6 percent injected dose [%ID]/g × 103 vs 5.7 ± 1.2 %ID/g × 103 [mean ± SEM], P <.001). In parallel with these findings, FDG uptake, as determined by PET, was higher in atherosclerotic aortas (standardized uptake value for atherosclerotic aortas vs control aortas, 0.68 ± 0.06 vs 0.13 ± 0.01; P <.001). Moreover, macrophage density, assessed histologically, correlated with noninvasive (PET) measurements of FDG uptake (r = 0.93, P <.0001). In contrast to this finding, FDG uptake did not correlate with either aortic wall thickness or smooth muscle cell staining of the specimens.

Conclusion

These data show that FDG accumulates in macrophage-rich atherosclerotic plaques and demonstrate that vascular macrophage activity can be quantified noninvasively with FDG-PET. As such, measurement of vascular FDG uptake with PET holds promise for the noninvasive characterization of vascular inflammation.

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Author information

Authors and Affiliations

  1. Departments of Medicine (Cardiac Unit), USA

    Ahmed Tawakol, Henry Gewirtz & James E. Muller

  2. Departments of Radiology, USA

    Raymond Q. Migrino, Udo Hoffmann, Suhny Abbara & Thomas J. Brady

  3. Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.

    Stuart Houser & Alan J. Fischmanb

Authors
  1. Ahmed Tawakol
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  2. Raymond Q. Migrino
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  5. Stuart Houser
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  7. James E. Muller
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  9. Alan J. Fischmanb
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Additional information

This study was supported in part by grants from the Center for Integration of Medicine and Innovative Technology (A.T.), National Institutes of Health (NIH) RR16046 (A.T.), and NIH EB02102E20 (R.Q.M.).

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Tawakol, A., Migrino, R.Q., Hoffmann, U. et al. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 12, 294–301 (2005). https://doi.org/10.1016/j.nuclcard.2005.03.002

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