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

Title: PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis

Abstract

Upregulation of sphingosine-1-phosphate receptor 1 (S1PR1) expression in multiple sclerosis (MS) lesions is associated with neuroinflammatory response. This study investigated the correlation between neuroinflammation and S1PR1 expression in the spinal cord of an experimental autoimmune encephalomyelitis (EAE) rat model of MS, using the S1PR1 positron emission tomography (PET) radiotracer [11C]TZ3321. MicroPET imaging studies of [11C]TZ3321 were performed to measure uptake of [11C]TZ3321 in the spinal cord of EAE rats. Immunohistochemical staining was performed to confirm the overexpression of S1PR1 and other inflammatory biomarkers. MicroPET imaging demonstrated a 20–30 % increase in [11C]TZ3321 uptake in the lumbar spinal cord of EAE rats versus sham controls at 35–60 min post injection. The increased uptake of [11C]TZ3321 was correlated with the overexpression of S1PR1 in the lumbar spinal cord of EAE rats that was confirmed by immunohistochemical staining. Upregulated S1PR1 expression was associated with glial cell activation and immune cell infiltration. MicroPET imaging modality with a specific radioligand [11C]TZ3321 is able to assess the expression of S1PR1 in EAE rat lumbar spinal cord. This may provide a new approach to the assessment of neuroinflammatory response in MS and other inflammatory diseases.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Washington Univ. School of Medicine, St. Louis, MO (United States)
Publication Date:
Research Org.:
Washington Univ., St. Louis, MO (United States). School of Medicine
Sponsoring Org.:
USDOE
OSTI Identifier:
1463267
Grant/Contract Number:  
SC0008432
Resource Type:
Accepted Manuscript
Journal Name:
Molecular Imaging and Biology (Print)
Additional Journal Information:
Journal Name: Molecular Imaging and Biology (Print); Journal Volume: 18; Journal Issue: 5; Journal ID: ISSN 1536-1632
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Liu, Hui, Jin, Hongjun, Yue, Xuyi, Luo, Zonghua, Liu, Chunling, Rosenberg, Adam J., and Tu, Zhude. PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis. United States: N. p., 2016. Web. doi:10.1007/s11307-016-0944-y.
Liu, Hui, Jin, Hongjun, Yue, Xuyi, Luo, Zonghua, Liu, Chunling, Rosenberg, Adam J., & Tu, Zhude. PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis. United States. doi:10.1007/s11307-016-0944-y.
Liu, Hui, Jin, Hongjun, Yue, Xuyi, Luo, Zonghua, Liu, Chunling, Rosenberg, Adam J., and Tu, Zhude. Mon . "PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis". United States. doi:10.1007/s11307-016-0944-y. https://www.osti.gov/servlets/purl/1463267.
@article{osti_1463267,
title = {PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis},
author = {Liu, Hui and Jin, Hongjun and Yue, Xuyi and Luo, Zonghua and Liu, Chunling and Rosenberg, Adam J. and Tu, Zhude},
abstractNote = {Upregulation of sphingosine-1-phosphate receptor 1 (S1PR1) expression in multiple sclerosis (MS) lesions is associated with neuroinflammatory response. This study investigated the correlation between neuroinflammation and S1PR1 expression in the spinal cord of an experimental autoimmune encephalomyelitis (EAE) rat model of MS, using the S1PR1 positron emission tomography (PET) radiotracer [11C]TZ3321. MicroPET imaging studies of [11C]TZ3321 were performed to measure uptake of [11C]TZ3321 in the spinal cord of EAE rats. Immunohistochemical staining was performed to confirm the overexpression of S1PR1 and other inflammatory biomarkers. MicroPET imaging demonstrated a 20–30 % increase in [11C]TZ3321 uptake in the lumbar spinal cord of EAE rats versus sham controls at 35–60 min post injection. The increased uptake of [11C]TZ3321 was correlated with the overexpression of S1PR1 in the lumbar spinal cord of EAE rats that was confirmed by immunohistochemical staining. Upregulated S1PR1 expression was associated with glial cell activation and immune cell infiltration. MicroPET imaging modality with a specific radioligand [11C]TZ3321 is able to assess the expression of S1PR1 in EAE rat lumbar spinal cord. This may provide a new approach to the assessment of neuroinflammatory response in MS and other inflammatory diseases.},
doi = {10.1007/s11307-016-0944-y},
journal = {Molecular Imaging and Biology (Print)},
number = 5,
volume = 18,
place = {United States},
year = {2016},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Role of Sphingosine 1-Phosphate (S1P) Receptor 1 in Experimental Autoimmune Encephalomyelitis —II
journal, January 2013

  • Seki, Noriyasu; Kataoka, Hirotoshi; Sugahara, Kunio
  • Pharmacology & Pharmacy, Vol. 04, Issue 08
  • DOI: 10.4236/pp.2013.48090

An 18-kDa Translocator Protein (TSPO) Polymorphism Explains Differences in Binding Affinity of the PET Radioligand PBR28
journal, October 2011

  • Owen, David R.; Yeo, Astrid J.; Gunn, Roger N.
  • Journal of Cerebral Blood Flow & Metabolism, Vol. 32, Issue 1
  • DOI: 10.1038/jcbfm.2011.147

Mixed-Affinity Binding in Humans with 18-kDa Translocator Protein Ligands
journal, December 2010


Fingolimod for Multiple Sclerosis
journal, January 2012

  • Pelletier, Daniel; Hafler, David A.
  • New England Journal of Medicine, Vol. 366, Issue 4
  • DOI: 10.1056/NEJMct1101691

A Genetic Polymorphism for Translocator Protein 18 Kda Affects both in Vitro and in Vivo Radioligand Binding in Human Brain to this Putative Biomarker of Neuroinflammation
journal, September 2012

  • Kreisl, William C.; Jenko, Kimberly J.; Hines, Christina S.
  • Journal of Cerebral Blood Flow & Metabolism, Vol. 33, Issue 1
  • DOI: 10.1038/jcbfm.2012.131

Pathological mechanisms in progressive multiple sclerosis
journal, February 2015


Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS): EAE as model for MS
journal, October 2011


Multiple sclerosis—a quiet revolution
journal, February 2015

  • Ransohoff, Richard M.; Hafler, David A.; Lucchinetti, Claudia F.
  • Nature Reviews Neurology, Vol. 11, Issue 3
  • DOI: 10.1038/nrneurol.2015.14

Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data
journal, September 1996


Models of autoimmune demyelination in the central nervous system: on the way to translational medicine
journal, October 2009

  • Linker, Ralf A.; Lee, De-Hyung
  • Experimental & Translational Stroke Medicine, Vol. 1, Issue 1
  • DOI: 10.1186/2040-7378-1-5

FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation
journal, December 2010

  • Choi, J. W.; Gardell, S. E.; Herr, D. R.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 2
  • DOI: 10.1073/pnas.1014154108

Graphical Analysis of Reversible Radioligand Binding from Time—Activity Measurements Applied to [ N - 11 C-Methyl]-(−)-Cocaine PET Studies in Human Subjects
journal, September 1990

  • Logan, Jean; Fowler, Joanna S.; Volkow, Nora D.
  • Journal of Cerebral Blood Flow & Metabolism, Vol. 10, Issue 5
  • DOI: 10.1038/jcbfm.1990.127

Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
journal, August 2013

  • Kunkel, Gregory T.; Maceyka, Michael; Milstien, Sheldon
  • Nature Reviews Drug Discovery, Vol. 12, Issue 9
  • DOI: 10.1038/nrd4099

Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis
journal, April 1999


Role of Sphingosine 1-Phosphate (S1P) Receptor 1 in Experimental Autoimmune Encephalomyelitis —I
journal, January 2013

  • Seki, Noriyasu; Maeda, Yasuhiro; Kataoka, Hirotoshi
  • Pharmacology & Pharmacy, Vol. 04, Issue 08
  • DOI: 10.4236/pp.2013.48089

Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis
journal, June 2010


Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
journal, October 2010

  • Brinkmann, Volker; Billich, Andreas; Baumruker, Thomas
  • Nature Reviews Drug Discovery, Vol. 9, Issue 11
  • DOI: 10.1038/nrd3248

A Sphingosine-1-Phosphate Receptor 1-Directed Agonist Reduces Central Nervous System Inflammation in a Plasmacytoid Dendritic Cell-Dependent Manner
journal, August 2012

  • Galicia-Rosas, Georgina; Pikor, Natalia; Schwartz, Jordan A.
  • The Journal of Immunology, Vol. 189, Issue 7
  • DOI: 10.4049/jimmunol.1102261

An update on the biology of sphingosine 1-phosphate receptors
journal, January 2014

  • Blaho, Victoria A.; Hla, Timothy
  • Journal of Lipid Research, Vol. 55, Issue 8
  • DOI: 10.1194/jlr.R046300

Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation
journal, September 2007

  • Kebir, Hania; Kreymborg, Katharina; Ifergan, Igal
  • Nature Medicine, Vol. 13, Issue 10
  • DOI: 10.1038/nm1651

A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis
journal, February 2010

  • Kappos, Ludwig; Radue, Ernst-Wilhelm; O'Connor, Paul
  • New England Journal of Medicine, Vol. 362, Issue 5
  • DOI: 10.1056/NEJMoa0909494

A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury
journal, February 2016


Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic molecules
journal, March 2009

  • Marsolais, David; Rosen, Hugh
  • Nature Reviews Drug Discovery, Vol. 8, Issue 4
  • DOI: 10.1038/nrd2356

Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation
journal, September 2013

  • Garris, Christopher S.; Wu, Linfeng; Acharya, Swati
  • Nature Immunology, Vol. 14, Issue 11
  • DOI: 10.1038/ni.2730

Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands
journal, May 2007

  • Innis, Robert B.; Cunningham, Vincent J.; Delforge, Jacques
  • Journal of Cerebral Blood Flow & Metabolism, Vol. 27, Issue 9
  • DOI: 10.1038/sj.jcbfm.9600493

Synthesis of fluorinated analogues of sphingosine-1-phosphate antagonists as potential radiotracers for molecular imaging using positron emission tomography
journal, October 2014

  • Prasad, Vysakh Pushpa; Wagner, Stefan; Keul, Petra
  • Bioorganic & Medicinal Chemistry, Vol. 22, Issue 19
  • DOI: 10.1016/j.bmc.2014.08.009

Mechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis
journal, January 2010


Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the Cc Chemokine Receptor (Ccr2)
journal, October 2000

  • Izikson, Leonid; Klein, Robyn S.; Charo, Israel F.
  • The Journal of Experimental Medicine, Vol. 192, Issue 7
  • DOI: 10.1084/jem.192.7.1075

BZM055, an Iodinated Radiotracer Candidate for PET and SPECT Imaging of Myelin and FTY720 Brain Distribution
journal, January 2011

  • Briard, Emmanuelle; Orain, David; Beerli, Christian
  • ChemMedChem, Vol. 6, Issue 4
  • DOI: 10.1002/cmdc.201000477

S1P 1 Receptor Modulation with Cyclical Recovery from Lymphopenia Ameliorates Mouse Model of Multiple Sclerosis
journal, October 2011

  • Gonzalez-Cabrera, Pedro J.; Cahalan, Stuart M.; Nguyen, Nhan
  • Molecular Pharmacology, Vol. 81, Issue 2
  • DOI: 10.1124/mol.111.076109

Fingolimod phosphate promotes the neuroprotective effects of microglia
journal, March 2013


Synthesis and Evaluation of Fluorinated Fingolimod (FTY720) Analogues for Sphingosine-1-Phosphate Receptor Molecular Imaging by Positron Emission Tomography
journal, April 2015

  • Shaikh, Rizwan S.; Schilson, Stefanie S.; Wagner, Stefan
  • Journal of Medicinal Chemistry, Vol. 58, Issue 8
  • DOI: 10.1021/jm502021d

PET Imaging of Disease Progression and Treatment Effects in the Experimental Autoimmune Encephalomyelitis Rat Model
journal, June 2014

  • de Paula Faria, D.; Vlaming, M. L. H.; Copray, S. C. V. M.
  • Journal of Nuclear Medicine, Vol. 55, Issue 8
  • DOI: 10.2967/jnumed.114.137216