FDG–PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis

  • John R. Davies
  • David Izquierdo-Garcia
  • James H. F. Rudd
  • Nichola Figg
  • Hugh K. Richards
  • Joseph L. E. Bird
  • Franklin I. Aigbirhio
  • Anthony P. Davenport
  • Peter L. Weissberg
  • Tim D. Fryer
  • Elizabeth A. Warburton
Original Paper

Abstract

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of 18F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS). In vivo and ex vivo microPET, ex vivo well counting and histological quantification of the atherosclerotic aortas were performed for all groups. Macrophage density was greater in the HC group than the LCS group (5.1 ± 1.4% vs. 0.6 ± 0.7%, P < 0.001) with a trend towards greater macrophage density in LCS compared to controls (P = 0.08). There was a strong correlation across all groups between macrophage density and standardized uptake value (SUV) derived from ex vivo microPET (r = 0.95, P < 0.001) and well counting (r = 0.96, P < 0.001). Ex vivo FDG SUV was significantly different between the three groups (P < 0.001). However, the correlation between in vivo microPET FDG SUV and macrophage density was insignificant (r = 0.16, P = 0.57) with no statistical differences in FDG SUV seen between the three groups. This study confirms that in an animal model of inflamed and non-inflamed atherosclerosis, significant differences in FDG SUV allow differentiation of highly inflamed atherosclerotic aortas from those stabilized by statin therapy and low cholesterol diet and controls.

Keywords

PET FDG Inflammation Atherosclerosis Animal model 

Notes

Acknowledgments

This study was funded by programme grants from the British Heart Foundation. JRD, DI-G, JHFR, JLEB, APD, and PLW are all supported by grants from the British Heart Foundation (FG/03/013 and PS/02/001). EAW receives support from the Cambridge Biomedical Research Centre grant (NIHR). This work was also supported by an equipment grant (microPET) from the HEFCE and Merck Sharp and Dohme, Ltd. We would like to acknowledge the Wolfson Brain Imaging Centre radiochemistry staff for supplying the FDG.

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Copyright information

© Springer Science+Business Media, B.V. 2009

Authors and Affiliations

  • John R. Davies
    • 1
  • David Izquierdo-Garcia
    • 2
  • James H. F. Rudd
    • 1
  • Nichola Figg
    • 1
  • Hugh K. Richards
    • 3
  • Joseph L. E. Bird
    • 2
    • 4
  • Franklin I. Aigbirhio
    • 2
  • Anthony P. Davenport
    • 4
  • Peter L. Weissberg
    • 1
  • Tim D. Fryer
    • 2
  • Elizabeth A. Warburton
    • 5
  1. 1.Division of Cardiovascular MedicineUniversity of Cambridge, Addenbrooke’s HospitalCambridgeUK
  2. 2.Wolfson Brain Imaging CentreUniversity of Cambridge, Addenbrooke’s HospitalCambridgeUK
  3. 3.Department of NeurosurgeryUniversity of Cambridge, Addenbrooke’s HospitalCambridgeUK
  4. 4.Clinical Pharmacology UnitUniversity of Cambridge, Addenbrooke’s HospitalCambridgeUK
  5. 5.Clinical NeurosciencesUniversity of Cambridge, Addenbrooke’s HospitalCambridgeUK

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