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Localization of Deoxyglucose and Annexin A5 in Experimental Atheroma Correlates with Macrophage Infiltration but not Lipid Deposition in the Lesion

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Abstract

Purpose

The aim of this study was to understand the relationship of lipid deposition to the macrophage content, macrophage metabolism, and apoptosis in plaque. We compared the uptake of 2-deoxy-2-fluoro-D-[14C]glucose ([14C]FDG) and [99mTc]HYNIC-annexin V ([99mTc]annexin A5) with the lesion histology in apolipoprotein E knockout (apoE−/−) mice.

Procedures

Male apoE−/− mice (n = 9) were injected with [14C]FDG and [99mTc]annexin A5. Cryostat sections of aorta samples (n = 49) were used for dual-tracer autoradiography, and regional tracer uptake levels were evaluated. Lesions were identified histologically with Movat's pentachrome (AHA lesion phenotypes), Mac-2 staining (macrophage infiltration) and Oil Red O staining (lipid deposition).

Results

The highest uptakes of [14C]FDG (3.10 ± 1.50 %ID × kilogram per square millimeter) and [99mTc]annexin A5 (0.49 ± 0.20 %ID × kilogram per square millimeter) were shown in atheromatous lesions (types III and IV). Each tracer uptake showed better correlation with macrophage infiltration than lipid deposition ([14C]FDG, r = 0.44 vs. r = 0.14; [99mTc]annexin A5, r = 0.65 vs. r = 0.48).

Conclusions

Both tracers were concentrated in type III and IV atheromatous lesions which corresponded to macrophage infiltration rather than lipid deposition.

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Abbreviations

FDG:

2-Deoxy-2-fluoro-D-glucose

HYNIC:

Hydrazinonicotinamide

[99mTc]annexin A5:

[99mTc]HYNIC-annexin A5

apoE−/− mice:

Apolipoprotein E knockout mice

PET:

Positron emission tomography

CT:

Computed tomography

MRI:

Magnetic resonance image

TIA:

Transient ischemic attack

ARG:

Autoradiography

ROI:

Region of interest

ACS:

Acute coronary syndrome

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Acknowledgments

This study was partially supported by Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese government. This research was also partially supported by a Grant-in-Aid for General Scientific Research from the Japan Society for the Promotion of Science. The authors would like to thank the staff 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 the NCI-Frederick Cancer Research and Development Center for providing annexin A5.

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan

    Yan Zhao & Nagara Tamaki

  2. Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Songji Zhao

  3. Central Institute of Isotope Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Yuji Kuge

  4. Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    William H. Strauss

  5. Department of Pediatric Radiology, Stanford University School of Medicine, Palo Alto, CA, USA

    Francis G. Blankenberg

Authors
  1. Yan Zhao
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  2. Songji Zhao
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  3. Yuji Kuge
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  6. Nagara Tamaki
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Corresponding author

Correspondence to Yuji Kuge.

Additional information

Significance:

In this study we compared the lesion distribution of [99mTc]annexin A5 (marker of ongoing apoptosis) and [14C]FDG (marker of the increased metabolism of inflammatory cells) with lesion histology in atherosclerotic plaques of apoE−/− mice. This data clarified the pathophysiologic significance of molecular imaging using [99mTc]annexin A5 and [14C]FDG, indicated the potential of the two probes on unstable plaque detection, and suggested the reason why discrepancy may be observed between [18F]FDG imaging and other diagnostic imaging or clinical outcomes.

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Zhao, Y., Zhao, S., Kuge, Y. et al. Localization of Deoxyglucose and Annexin A5 in Experimental Atheroma Correlates with Macrophage Infiltration but not Lipid Deposition in the Lesion. Mol Imaging Biol 13, 712–720 (2011). https://doi.org/10.1007/s11307-010-0389-7

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  • DOI: https://doi.org/10.1007/s11307-010-0389-7

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