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

  • Yan Zhao
  • Yuji Kuge
  • Songji Zhao
  • Koichi Morita
  • Masayuki Inubushi
  • H. William Strauss
  • Francis G. Blankenberg
  • Nagara Tamaki
Original Article



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.


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).


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).


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.


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



This research was supported in part by Grant-in-Aid for General Scientific Research and Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan and from the Japan Society for the Promotion of Science and by a research grant for cardiovascular diseases from the Ministry of Health, Labour and Welfare (15C-5 and 16C-8). The authors would like to thank the staff members of the Department of Nuclear Medicine and Central Institute of Isotope Science, Hokkaido University, and the Facility of Radiology, Hokkaido University Medical Hospital for supporting this work. We also thank Theseus Imaging Corporation for providing annexin A5.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Yan Zhao
    • 1
  • Yuji Kuge
    • 2
    • 3
    • 4
  • Songji Zhao
    • 1
    • 2
  • Koichi Morita
    • 1
  • Masayuki Inubushi
    • 3
  • H. William Strauss
    • 5
  • Francis G. Blankenberg
    • 6
  • Nagara Tamaki
    • 1
  1. 1.Department of Nuclear Medicine, Graduate School of MedicineHokkaido UniversitySapporoJapan
  2. 2.Department of Tracer Kinetics, Graduate School of MedicineHokkaido UniversitySapporoJapan
  3. 3.Department of Molecular Imaging, Graduate School of MedicineHokkaido UniversitySapporoJapan
  4. 4.Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  5. 5.Department of Nuclear MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  6. 6.Department of Pediatric RadiologyStanford University School of MedicinePalo AltoUSA

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