European Journal of Nuclear Medicine and Molecular Imaging

, Volume 34, Issue 6, pp 889–899

99mTc-Annexin A5 for noninvasive characterization of atherosclerotic lesions: imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits

Authors

  • Seigo Ishino
    • Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
    • Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
    • Department of Molecular Imaging, Graduate School of MedicineHokkaido University
  • Nozomi Takai
    • Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Nagara Tamaki
    • Department of Nuclear Medicine, Graduate School of MedicineHokkaido University
  • H. William Strauss
    • Department of Nuclear MedicineMemorial Sloan-Kettering Cancer Center
  • Francis G. Blankenberg
    • Pediatric RadiologyStanford University School of Medicine
  • Masashi Shiomi
    • Institute for Experimental AnimalsKobe University School of Medicine
  • Hideo Saji
    • Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
Original Article

DOI: 10.1007/s00259-006-0289-x

Cite this article as:
Ishino, S., Kuge, Y., Takai, N. et al. Eur J Nucl Med Mol Imaging (2007) 34: 889. doi:10.1007/s00259-006-0289-x

Abstract

Purpose

Apoptosis is commonly observed in advanced atherosclerotic lesions. 99mTc-annexin A5 (99mTc-annexin V) has been proposed as a potential tracer for imaging apoptosis in atherosclerotic plaques. Accordingly, we determined the usefulness of 99mTc-annexin A5 as an atherosclerosis imaging tracer in a rabbit model (myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits; WHHLMI rabbits) of spontaneous atherosclerosis.

Methods

The WHHLMI and control rabbits were injected intravenously with 99mTc-annexin A5. After in vivo planar imaging, the radioactivity in the aorta was measured. Autoradiography, TUNEL staining, Azan-Mallory staining and immunohistological studies were performed serially throughout the aorta.

Results

99mTc-Annexin A5 accumulation in the aorta of the WHHLMI rabbits was 5.6-fold higher than in that of control rabbits. Autoradiography showed heterogeneous multifocal accumulation of 99mTc-annexin A5 in WHHLMI rabbits. 99mTc-Annexin A5 accumulation was highest in the atheromatous lesions (6.2 ± 2.5, %ID × BW/mm2 × 103), followed in decreasing order by neointimal (4.9 ± 1.3), fibroatheromatous (4.5 ± 1.9), and collagen-rich lesions (3.3 ± 1.4). The regional 99mTc-annexin A5 accumulation was significantly correlated with the TUNEL-positive cell density, macrophage density and “vulnerability index,” an index of the morphological destabilized characteristics. The in vivo imaging clearly visualized the atherosclerotic lesions in WHHLMI rabbits.

Conclusion

The present study in WHHLMI rabbits showed higher 99mTc-annexin A5 accumulation in grade IV atheroma than in other more stable lesions. 99mTc-Annexin A5 may be useful in identifying atheroma that is at higher risk for rupture and possibly in assessing the response to anti-atherosclerotic therapy.

Keywords

AtherosclerosisAnnexin VApoptosis imagingPlaqueRadiolabeled proteins

Copyright information

© Springer-Verlag 2007