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

Journal Article · · Molecular Imaging and Biology
 [1];  [2];  [2];  [2];  [2];  [2];  [2]
  1. Washington Univ. School of Medicine, St. Louis, MO (United States); OSTI
  2. Washington Univ. School of Medicine, St. Louis, MO (United States)
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.
Research Organization:
Washington Univ. School of Medicine, St. Louis, MO (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
SC0008432
OSTI ID:
1463267
Journal Information:
Molecular Imaging and Biology, Journal Name: Molecular Imaging and Biology Journal Issue: 5 Vol. 18; ISSN 1536-1632
Country of Publication:
United States
Language:
English

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Cited By (5)

PET Study of Sphingosine-1-Phosphate Receptor 1 Expression in Response to Vascular Inflammation in a Rat Model of Carotid Injury journal January 2017
Emerging PET Radiotracers and Targets for Imaging of Neuroinflammation in Neurodegenerative Diseases: Outlook Beyond TSPO journal January 2018
Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers journal April 2019
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
Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease journal January 2020

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