(99m)Tc-Annexin A5 for noninvasive characterization of atherosclerotic lesions: Imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits Journal Article


Authors: Ishino, S.; Kuge, Y.; Takai, N.; Tamaki, N.; Strauss, H. W.; Blankenberg, F. G.; Shiomi, M.; Saji, H.
Article Title: (99m)Tc-Annexin A5 for noninvasive characterization of atherosclerotic lesions: Imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits
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. © 2007 Springer-Verlag.
Keywords: controlled study; unclassified drug; nonhuman; methodology; technetium 99m; radiopharmaceuticals; animal; metabolism; animals; animal tissue; apoptosis; animal experiment; animal model; diagnostic imaging; histology; correlation analysis; chemistry; isotope labeling; heart infarction; atherosclerosis; radioactivity; radiopharmaceutical agent; scintiscanning; tracer; radioisotope; macrophage; macrophages; regression analysis; nick end labeling; hyperlipidemia; autoradiography; myocardial infarction; lipocortin 5; hyperlipidemias; rabbits; aorta; annexin a5; rabbit; annexin v; plaque; technetium; arteriosclerosis; immunohistology; annexin a5 tc 99m; apoptosis imaging; radiolabeled proteins
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 34
Issue: 6
ISSN: 1619-7070
Publisher: Springer  
Date Published: 2007-06-01
Start Page: 889
End Page: 899
Language: English
DOI: 10.1007/s00259-006-0289-x
PUBMED: 17216472
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: EJNMA" - "Source: Scopus"
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  1. Harry W Strauss
    164 Strauss