PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury
Sphingosine-1-phosphate receptor (S1PR) activation plays a key role in vascular inflammatory response. Here, we report in vivo validation of [ 11 C]TZ3321, a potent S1PR1 radioligand, for imaging vascular inflammation in a rat model of carotid injury. The right common carotid artery of male adult Sp...
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| Format: | Article |
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SAGE Publishing
2017-01-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012116689770 |
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| author | Hui Liu PhD, MD Hongjun Jin PhD Xuyi Yue PhD Junbin Han PhD Pamela Baum SRS Dana R. Abendschein PhD Zhude Tu PhD |
| author_facet | Hui Liu PhD, MD Hongjun Jin PhD Xuyi Yue PhD Junbin Han PhD Pamela Baum SRS Dana R. Abendschein PhD Zhude Tu PhD |
| author_sort | Hui Liu PhD, MD |
| collection | DOAJ |
| description | Sphingosine-1-phosphate receptor (S1PR) activation plays a key role in vascular inflammatory response. Here, we report in vivo validation of [ 11 C]TZ3321, a potent S1PR1 radioligand, for imaging vascular inflammation in a rat model of carotid injury. The right common carotid artery of male adult Sprague-Dawley rats was injured by balloon overinflation that denuded the endothelium and distended the vessel wall. Animals received a 60-minute micro-positron emission tomography (micro PET) scan with [ 11 C]TZ3321 at 72 hours after injury. Ex vivo autoradiography was also conducted. The expression and cellular location of S1PR1 were examined by immunohistological analysis. Three-dimensional (3D) reconstruction of the first 100-second microPET/computed tomography (CT) image indicated the location of bilateral common carotid arteries. [ 11 C]TZ3321 displayed significantly higher accumulation (standardized uptake values: 0.93 ± 0.07 vs 0.78 ± 0.09, n = 6, P = .001) in the injured carotid artery than in the contralateral side. Increased tracer uptake in the injured artery was confirmed by autoradiography (photostimulated luminescence measures: 85.5 ± 0.93 vs 71.48 ± 6.22, n = 2). Concordantly, high S1PR1expression was observed in infiltrated inflammatory cells in the injured artery. Our studies demonstrate [ 11 C]TZ3321 microPET is able to detect the acute upregulation of S1PR1 expression in inflamed carotid artery. Therefore, [ 11 C]TZ3321 has potential to be a PET radiotracer for detecting early inflammatory response and monitoring therapeutic efficacy of vascular inflammation. |
| format | Article |
| id | doaj-art-7ffa2890042b458dbe1724123cc53808 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-7ffa2890042b458dbe1724123cc538082025-02-03T10:07:51ZengSAGE PublishingMolecular Imaging1536-01212017-01-011610.1177/153601211668977010.1177_1536012116689770PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid InjuryHui Liu PhD, MD0Hongjun Jin PhD1Xuyi Yue PhD2Junbin Han PhD3Pamela Baum SRS4Dana R. Abendschein PhD5Zhude Tu PhD6 Department of Radiology, Washington University School of Medicine, St Louis, MO, USA Department of Radiology, Washington University School of Medicine, St Louis, MO, USA Department of Radiology, Washington University School of Medicine, St Louis, MO, USA Department of Radiology, Washington University School of Medicine, St Louis, MO, USA Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA Department of Radiology, Washington University School of Medicine, St Louis, MO, USASphingosine-1-phosphate receptor (S1PR) activation plays a key role in vascular inflammatory response. Here, we report in vivo validation of [ 11 C]TZ3321, a potent S1PR1 radioligand, for imaging vascular inflammation in a rat model of carotid injury. The right common carotid artery of male adult Sprague-Dawley rats was injured by balloon overinflation that denuded the endothelium and distended the vessel wall. Animals received a 60-minute micro-positron emission tomography (micro PET) scan with [ 11 C]TZ3321 at 72 hours after injury. Ex vivo autoradiography was also conducted. The expression and cellular location of S1PR1 were examined by immunohistological analysis. Three-dimensional (3D) reconstruction of the first 100-second microPET/computed tomography (CT) image indicated the location of bilateral common carotid arteries. [ 11 C]TZ3321 displayed significantly higher accumulation (standardized uptake values: 0.93 ± 0.07 vs 0.78 ± 0.09, n = 6, P = .001) in the injured carotid artery than in the contralateral side. Increased tracer uptake in the injured artery was confirmed by autoradiography (photostimulated luminescence measures: 85.5 ± 0.93 vs 71.48 ± 6.22, n = 2). Concordantly, high S1PR1expression was observed in infiltrated inflammatory cells in the injured artery. Our studies demonstrate [ 11 C]TZ3321 microPET is able to detect the acute upregulation of S1PR1 expression in inflamed carotid artery. Therefore, [ 11 C]TZ3321 has potential to be a PET radiotracer for detecting early inflammatory response and monitoring therapeutic efficacy of vascular inflammation.https://doi.org/10.1177/1536012116689770 |
| spellingShingle | Hui Liu PhD, MD Hongjun Jin PhD Xuyi Yue PhD Junbin Han PhD Pamela Baum SRS Dana R. Abendschein PhD Zhude Tu PhD PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury Molecular Imaging |
| title | PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury |
| title_full | PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury |
| title_fullStr | PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury |
| title_full_unstemmed | PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury |
| title_short | PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury |
| title_sort | pet study of sphingosine 1 phosphate receptor 1 expression in response to vascular inflammation in a rat model of carotid injury |
| url | https://doi.org/10.1177/1536012116689770 |
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