Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 34, Issue 11, pp 1747-1755

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

  • Yan ZhaoAffiliated withDepartment of Nuclear Medicine, Graduate School of Medicine, Hokkaido University
  • , Yuji KugeAffiliated withDepartment of Tracer Kinetics, Graduate School of Medicine, Hokkaido UniversityDepartment of Molecular Imaging, Graduate School of Medicine, Hokkaido UniversityDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
  • , Songji ZhaoAffiliated withDepartment of Nuclear Medicine, Graduate School of Medicine, Hokkaido UniversityDepartment of Tracer Kinetics, Graduate School of Medicine, Hokkaido University
  • , Koichi MoritaAffiliated withDepartment of Nuclear Medicine, Graduate School of Medicine, Hokkaido University
  • , Masayuki InubushiAffiliated withDepartment of Molecular Imaging, Graduate School of Medicine, Hokkaido University
  • , H. William StraussAffiliated withDepartment of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center
  • , Francis G. BlankenbergAffiliated withDepartment of Pediatric Radiology, Stanford University School of Medicine
  • , Nagara TamakiAffiliated withDepartment of Nuclear Medicine, Graduate School of Medicine, Hokkaido University Email author 

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Abstract

Purpose

99mTc-annexin A5, a marker of ongoing apoptosis, and 18F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE−/− mice.

Methods

Male ApoE−/− mice (n = 12–14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, 99mTc-annexin A5 or 18F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development).

Results

Both 99mTc-annexin A5 and 18F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for 18F-FDG (mean, 56.07 %ID×kg/m2) than for 99mTc-annexin A5 (mean, 10.38 %ID×kg/m2). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for 99mTc-annexin A5; r = 0.56, p < 0.05 for 18F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score <0.5) were significantly higher for 99mTc-annexin A5 than for 18F-FDG (f = 4.73, p = 0.03).

Conclusion

Both 99mTc-annexin A5 and 18F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of 18F-FDG may be advantageous for lesion detection, whereas the preferential uptake of 99mTc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation.

Keywords

Atherosclerosis Apoptosis 99mTc-annexin A5 18F-FDG Apolipoprotein E-knockout mouse