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Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs
BACKGROUND: Receptor for advanced glycated end product (RAGE) expression is a prominent feature of atherosclerosis. We have previously shown in apoE null mice uptake of a radiolabeled anti-RAGE antibody in atherosclerotic plaque and now evaluate RAGE-directed imaging to identify advanced plaques in...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078320/ https://www.ncbi.nlm.nih.gov/pubmed/25006545 http://dx.doi.org/10.1186/s13550-014-0026-6 |
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author | Johnson, Lynne L Tekabe, Yared Kollaros, Maria Eng, George Bhatia, Ketan Li, Chong Krueger, Christian G Shanmuganayagam, Dhanansayan Schmidt, Ann Marie |
author_facet | Johnson, Lynne L Tekabe, Yared Kollaros, Maria Eng, George Bhatia, Ketan Li, Chong Krueger, Christian G Shanmuganayagam, Dhanansayan Schmidt, Ann Marie |
author_sort | Johnson, Lynne L |
collection | PubMed |
description | BACKGROUND: Receptor for advanced glycated end product (RAGE) expression is a prominent feature of atherosclerosis. We have previously shown in apoE null mice uptake of a radiolabeled anti-RAGE antibody in atherosclerotic plaque and now evaluate RAGE-directed imaging to identify advanced plaques in a large animal model. METHODS: Nine hyperlipidemic (HL) pigs were injected with 603.1 ± 129.5 MBq of (99m)Tc-anti-RAGE F(ab′)(2), and after 6 h (blood pool clearance), they underwent single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of the neck, thorax, and hind limbs. Two HL pigs received (99m)Tc non-immune IgG F(ab′)(2), and three farm pigs were injected with (99m)Tc-anti-RAGE F(ab′)(2). After imaging, the pigs were euthanized. The aorta from the root to bifurcation was dissected, and the innominates, proximal carotids, and coronaries were dissected and counted, stained for H&E and RAGE, and AHA-classified. RESULTS: On pathology, 24% of the arterial segments showed AHA class III or IV lesions, and these lesions were confined almost exclusively to coronaries and carotids with % stenosis from 15% to 65%. Scatter plots of %ID/g for class III/IV vs. I/II lesions showed almost complete separation. Focal vascular uptake of tracer visualized on SPECT scans corresponded to class III/IV lesions in the coronary and carotid vessels. In addition, uptake in the hind limbs was noted in the HL pigs and corresponded to RAGE staining of small arteries in the muscle sections. Correlations for the vascular lesions were r = 0.747, P = 0.001 for %ID vs. %ID/g and r = 0.83, P = 0.002 for %ID/g vs. % RAGE staining. CONCLUSIONS: Uptake of radiolabeled anti-RAGE antibody in coronary and carotid fibroatheroma and in the small arteries of the hind limbs in a relevant large animal model of atherosclerosis supports the important role of RAGE in atherosclerosis and peripheral artery disease as a target for imaging and treatment. |
format | Online Article Text |
id | pubmed-4078320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer |
record_format | MEDLINE/PubMed |
spelling | pubmed-40783202014-07-08 Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs Johnson, Lynne L Tekabe, Yared Kollaros, Maria Eng, George Bhatia, Ketan Li, Chong Krueger, Christian G Shanmuganayagam, Dhanansayan Schmidt, Ann Marie EJNMMI Res Original Research BACKGROUND: Receptor for advanced glycated end product (RAGE) expression is a prominent feature of atherosclerosis. We have previously shown in apoE null mice uptake of a radiolabeled anti-RAGE antibody in atherosclerotic plaque and now evaluate RAGE-directed imaging to identify advanced plaques in a large animal model. METHODS: Nine hyperlipidemic (HL) pigs were injected with 603.1 ± 129.5 MBq of (99m)Tc-anti-RAGE F(ab′)(2), and after 6 h (blood pool clearance), they underwent single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of the neck, thorax, and hind limbs. Two HL pigs received (99m)Tc non-immune IgG F(ab′)(2), and three farm pigs were injected with (99m)Tc-anti-RAGE F(ab′)(2). After imaging, the pigs were euthanized. The aorta from the root to bifurcation was dissected, and the innominates, proximal carotids, and coronaries were dissected and counted, stained for H&E and RAGE, and AHA-classified. RESULTS: On pathology, 24% of the arterial segments showed AHA class III or IV lesions, and these lesions were confined almost exclusively to coronaries and carotids with % stenosis from 15% to 65%. Scatter plots of %ID/g for class III/IV vs. I/II lesions showed almost complete separation. Focal vascular uptake of tracer visualized on SPECT scans corresponded to class III/IV lesions in the coronary and carotid vessels. In addition, uptake in the hind limbs was noted in the HL pigs and corresponded to RAGE staining of small arteries in the muscle sections. Correlations for the vascular lesions were r = 0.747, P = 0.001 for %ID vs. %ID/g and r = 0.83, P = 0.002 for %ID/g vs. % RAGE staining. CONCLUSIONS: Uptake of radiolabeled anti-RAGE antibody in coronary and carotid fibroatheroma and in the small arteries of the hind limbs in a relevant large animal model of atherosclerosis supports the important role of RAGE in atherosclerosis and peripheral artery disease as a target for imaging and treatment. Springer 2014-06-11 /pmc/articles/PMC4078320/ /pubmed/25006545 http://dx.doi.org/10.1186/s13550-014-0026-6 Text en Copyright © 2014 Johnson et al.; licensee Springer http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Original Research Johnson, Lynne L Tekabe, Yared Kollaros, Maria Eng, George Bhatia, Ketan Li, Chong Krueger, Christian G Shanmuganayagam, Dhanansayan Schmidt, Ann Marie Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs |
title | Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs |
title_full | Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs |
title_fullStr | Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs |
title_full_unstemmed | Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs |
title_short | Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs |
title_sort | imaging rage expression in atherosclerotic plaques in hyperlipidemic pigs |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078320/ https://www.ncbi.nlm.nih.gov/pubmed/25006545 http://dx.doi.org/10.1186/s13550-014-0026-6 |
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