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VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs
BACKGROUND: New therapies to treat diabetic peripheral artery disease (PAD) require target-specific non-invasive imaging modalities to follow efficacy. As a translational study, we performed targeted imaging of receptors for vascular endothelial growth factor (VEGF) in response to anterior femoral a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218044/ https://www.ncbi.nlm.nih.gov/pubmed/32399850 http://dx.doi.org/10.1186/s13550-020-00626-0 |
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author | Johnson, Lynne L. Johnson, Jordan Ali, Ziad Tekabe, Yared Ober, Rebecca Geist, Gail McLuckie, Alicia Safarov, Aram Holland, April Zhang, Geping Backer, Marina Backer, Joseph |
author_facet | Johnson, Lynne L. Johnson, Jordan Ali, Ziad Tekabe, Yared Ober, Rebecca Geist, Gail McLuckie, Alicia Safarov, Aram Holland, April Zhang, Geping Backer, Marina Backer, Joseph |
author_sort | Johnson, Lynne L. |
collection | PubMed |
description | BACKGROUND: New therapies to treat diabetic peripheral artery disease (PAD) require target-specific non-invasive imaging modalities to follow efficacy. As a translational study, we performed targeted imaging of receptors for vascular endothelial growth factor (VEGF) in response to anterior femoral artery occlusion (FAO) in Yucatan minipigs and compare the normal response to response in diabetic Yucatan minipigs. METHODS: Eleven Yucatan minipigs, 6 non-diabetic (non-D) and 5 purpose bred diabetic (D) (Sinclair, Auxvasse MO), underwent intravascular total occlusion of the anterior femoral artery (FA). At days 1 and 28, pigs underwent SPECT/CT (201)Tl hindlimb perfusion imaging and at day 7 were injected with [(99m)Tc]DOTA-PEG-scVEGF (scV/Tc) tracer targeting VEGF receptor, and underwent biopsies of the hindlimb muscles for gamma counting and histology, followed by imaging. One day after the final scan, pigs underwent contrast angiography of the lower extremities. Counts from scans were converted to percentage injected activity (%IA). RESULTS: Perfusion was lower in the occluded hindlimb compared to non-occluded on day 1 in both the D and non-D pigs. At day 7, scV/Tc count ratio of counts from ROIs drawn in proximal gastrocnemius muscle for the occluded over non-occluded limb was significantly higher in non-D vs. D pigs (1.32 ± 0.06 vs. 1.04 ± 0.13, P = 0.02) reflecting higher level of angiogenesis. Perfusion increased between days 1 and 28 in the muscles in the occluded limb for the non-diabetic pigs while the diabetic pig showed no increase (+ 0.13 ± 0.08 %IA vs. − 0.13 ± 0.11, P = 0.003). The anterior FA showed poor contrast filling beyond occluder and qualitatively fewer bridging collaterals compared to non-D pigs at 28 days. CONCLUSION: VEGF receptor targeted imaging showed the effects of diabetes to suppress angiogenesis in response to occlusion of the anterior femoral artery of purpose bred diabetic Yucatan minipigs and indicates potential applicability as a marker to follow efficacy of novel therapies to improve blood flow by stimulating angiogenesis in diabetic PAD. |
format | Online Article Text |
id | pubmed-7218044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-72180442020-05-15 VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs Johnson, Lynne L. Johnson, Jordan Ali, Ziad Tekabe, Yared Ober, Rebecca Geist, Gail McLuckie, Alicia Safarov, Aram Holland, April Zhang, Geping Backer, Marina Backer, Joseph EJNMMI Res Original Research BACKGROUND: New therapies to treat diabetic peripheral artery disease (PAD) require target-specific non-invasive imaging modalities to follow efficacy. As a translational study, we performed targeted imaging of receptors for vascular endothelial growth factor (VEGF) in response to anterior femoral artery occlusion (FAO) in Yucatan minipigs and compare the normal response to response in diabetic Yucatan minipigs. METHODS: Eleven Yucatan minipigs, 6 non-diabetic (non-D) and 5 purpose bred diabetic (D) (Sinclair, Auxvasse MO), underwent intravascular total occlusion of the anterior femoral artery (FA). At days 1 and 28, pigs underwent SPECT/CT (201)Tl hindlimb perfusion imaging and at day 7 were injected with [(99m)Tc]DOTA-PEG-scVEGF (scV/Tc) tracer targeting VEGF receptor, and underwent biopsies of the hindlimb muscles for gamma counting and histology, followed by imaging. One day after the final scan, pigs underwent contrast angiography of the lower extremities. Counts from scans were converted to percentage injected activity (%IA). RESULTS: Perfusion was lower in the occluded hindlimb compared to non-occluded on day 1 in both the D and non-D pigs. At day 7, scV/Tc count ratio of counts from ROIs drawn in proximal gastrocnemius muscle for the occluded over non-occluded limb was significantly higher in non-D vs. D pigs (1.32 ± 0.06 vs. 1.04 ± 0.13, P = 0.02) reflecting higher level of angiogenesis. Perfusion increased between days 1 and 28 in the muscles in the occluded limb for the non-diabetic pigs while the diabetic pig showed no increase (+ 0.13 ± 0.08 %IA vs. − 0.13 ± 0.11, P = 0.003). The anterior FA showed poor contrast filling beyond occluder and qualitatively fewer bridging collaterals compared to non-D pigs at 28 days. CONCLUSION: VEGF receptor targeted imaging showed the effects of diabetes to suppress angiogenesis in response to occlusion of the anterior femoral artery of purpose bred diabetic Yucatan minipigs and indicates potential applicability as a marker to follow efficacy of novel therapies to improve blood flow by stimulating angiogenesis in diabetic PAD. Springer Berlin Heidelberg 2020-05-12 /pmc/articles/PMC7218044/ /pubmed/32399850 http://dx.doi.org/10.1186/s13550-020-00626-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Research Johnson, Lynne L. Johnson, Jordan Ali, Ziad Tekabe, Yared Ober, Rebecca Geist, Gail McLuckie, Alicia Safarov, Aram Holland, April Zhang, Geping Backer, Marina Backer, Joseph VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs |
title | VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs |
title_full | VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs |
title_fullStr | VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs |
title_full_unstemmed | VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs |
title_short | VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs |
title_sort | vegf receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic yucatan minipigs |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218044/ https://www.ncbi.nlm.nih.gov/pubmed/32399850 http://dx.doi.org/10.1186/s13550-020-00626-0 |
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