TY - JOUR
T1 - 99mTc-Annexin A5 for noninvasive characterization of atherosclerotic lesions
T2 - Imaging and histological studies in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits
AU - Ishino, Seigo
AU - Kuge, Yuji
AU - Takai, Nozomi
AU - Tamaki, Nagara
AU - Strauss, H. William
AU - Blankenberg, Francis G.
AU - Shiomi, Masashi
AU - Saji, Hideo
N1 - Funding Information:
Acknowledgements This work was partly supported by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and from the Japan Society for the Promotion of Science, by a research grant for cardiovascular diseases from the Ministry of Health, Labour and Welfare (15C-5 and 16C-8) and by the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science.” We would like to thank Theseus Imaging Corporation for providing annexin A5.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
KW - Annexin V
KW - Apoptosis imaging
KW - Atherosclerosis
KW - Plaque
KW - Radiolabeled proteins
UR - https://www.scopus.com/pages/publications/34249104229
U2 - 10.1007/s00259-006-0289-x
DO - 10.1007/s00259-006-0289-x
M3 - Article
C2 - 17216472
AN - SCOPUS:34249104229
SN - 1619-7070
VL - 34
SP - 889
EP - 899
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 6
ER -