skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury

Journal Article · · Molecular Imaging
 [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
+ Show Author Affiliations

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.

Research Organization:
Washington Univ., St. Louis, MO (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States)
Grant/Contract Number:
SC0008432; SC0012737; R01NS075527; MH092797
OSTI ID:
1368403
Journal Information:
Molecular Imaging, Vol. 16; ISSN 1536-0121
Publisher:
SAGECopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 18 works
Citation information provided by
Web of Science

References (20)

Apoptosis Signal–Regulating Kinase 1 Deficiency Attenuates Vascular Injury–Induced Neointimal Hyperplasia by Suppressing Apoptosis in Smooth Muscle Cells journal February 2013
PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis journal March 2016
Sphingosine 1-Phosphate Mediates Hyperalgesia via a Neutrophil-Dependent Mechanism journal January 2013
Estradiol and Progestins Differentially Modulate Leukocyte Infiltration After Vascular Injury journal January 2004
The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment journal August 2014
PET imaging of inflammation in atherosclerosis journal June 2014
Protective and pathogenic functions of macrophage subsets journal October 2011
Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo journal March 2014
Synthesis and biological evaluation of γ-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists journal January 2007
Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis journal April 2011
The role of the adventitia in vascular inflammation journal September 2007
Neutrophils and immunity: challenges and opportunities journal February 2006
Rat Carotid Artery Balloon Injury Model book January 2007
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1 journal January 2004
Sphingosine-1-Phosphate Receptor Subtypes Differentially Regulate Smooth Muscle Cell Phenotype journal August 2008
Sphingosine 1-Phosphate: A Regulator of Arterial Lesions journal October 2009
An update on the biology of sphingosine 1-phosphate receptors journal January 2014
Fingolimod treatment for multiple sclerosis Patients What Do We Do with Varicella? journal October 2011
KRP-203, Sphingosine 1-Phosphate Receptor Type 1 Agonist, Ameliorates Atherosclerosis in LDL-R −/− Mice journal July 2013
Inflammation and Vascular Injury journal January 2012

Cited By (2)

Syntheses and in vitro biological evaluation of S1PR1 ligands and PET studies of four F-18 labeled radiotracers in the brain of nonhuman primates journal January 2018
Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics journal December 2018

Similar Records

Design, Synthesis, and In Vitro and In Vivo Evaluation of an 18 F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer
Journal Article · Thu Jun 09 00:00:00 EDT 2016 · Journal of Medicinal Chemistry · OSTI ID:1368403
+4 more
A potent and selective C-11 labeled PET tracer for imaging sphingosine-1-phosphate receptor 2 in the CNS demonstrates sexually dimorphic expression
Journal Article · Tue Jun 09 00:00:00 EDT 2015 · Organic and Biomolecular Chemistry · OSTI ID:1368403
+3 more
Role of sphingosine‐1‐phosphate receptors in vascular injury of inflammatory bowel disease
Journal Article · Wed Feb 17 00:00:00 EST 2021 · Journal of Cellular and Molecular Medicine · OSTI ID:1368403
+2 more

Related Subjects

60 APPLIED LIFE SCIENCES
sphingosine-1-phosphate receptor 1
vascular inflammation
radioligand
PET