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Title: 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 [ 11C]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 [ 11C]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. [ 11C]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 [ 11C]TZ3321 microPET is able to detect the acute upregulation of S1PR1 expressionmore » in inflamed carotid artery. Therefore, [ 11C]TZ3321 has potential to be a PET radiotracer for detecting early inflammatory response and monitoring therapeutic efficacy of vascular inflammation.« less
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [1]
  1. Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Radiology
  2. Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Internal Medicine. Center for Cardiovascular Research
Publication Date:
Grant/Contract Number:
SC0008432; SC0012737; R01NS075527; MH092797
Type:
Accepted Manuscript
Journal Name:
Molecular Imaging
Additional Journal Information:
Journal Volume: 16; Journal ID: ISSN 1536-0121
Publisher:
SAGE
Research Org:
Washington Univ., St. Louis, MO (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; sphingosine-1-phosphate receptor 1; vascular inflammation; radioligand; PET
OSTI Identifier:
1368403

Liu, Hui, Jin, Hongjun, Yue, Xuyi, Han, Junbin, Baum, Pamela, Abendschein, Dana R., and Tu, Zhude. PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury. United States: N. p., Web. doi:10.1177/1536012116689770.
Liu, Hui, Jin, Hongjun, Yue, Xuyi, Han, Junbin, Baum, Pamela, Abendschein, Dana R., & Tu, Zhude. PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury. United States. doi:10.1177/1536012116689770.
Liu, Hui, Jin, Hongjun, Yue, Xuyi, Han, Junbin, Baum, Pamela, Abendschein, Dana R., and Tu, Zhude. 2017. "PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury". United States. doi:10.1177/1536012116689770. https://www.osti.gov/servlets/purl/1368403.
@article{osti_1368403,
title = {PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury},
author = {Liu, Hui and Jin, Hongjun and Yue, Xuyi and Han, Junbin and Baum, Pamela and Abendschein, Dana R. and Tu, Zhude},
abstractNote = {Sphingosine-1-phosphate receptor (S1PR) activation plays a key role in vascular inflammatory response. Here, we report in vivo validation of [11C]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 [11C]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. [11C]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 [11C]TZ3321 microPET is able to detect the acute upregulation of S1PR1 expression in inflamed carotid artery. Therefore, [11C]TZ3321 has potential to be a PET radiotracer for detecting early inflammatory response and monitoring therapeutic efficacy of vascular inflammation.},
doi = {10.1177/1536012116689770},
journal = {Molecular Imaging},
number = ,
volume = 16,
place = {United States},
year = {2017},
month = {1}
}