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 [(11)C]TZ3321.
  
  
  
  MicroPET imaging studies of [(11)C]TZ3321 were performed to measure uptake of [(11)C]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 [(11)C]TZ3321 uptake in the lumbar spinal cord of EAE rats versus sham controls at 35-60 min post injection. The increased uptake of [(11)C]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 [(11)C]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.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Xuyi
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Zonghua
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Chunling
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rosenberg
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA. tuz@mir.wustl.edu.
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011917:Rats, Inbred Lew; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D000081025:Sphingosine-1-Phosphate Receptors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D066127:White Matter / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D020381:Interleukin-17; D049349:Receptors, Lysosphingolipid; C578616:S1PR1 protein, rat; D000081025:Sphingosine-1-Phosphate Receptors
keywords: Experimental autoimmune encephalomyelitis; Multiple sclerosis; Neuroinflammation; PET imaging; Radiotracer; Sphingosine-1-phosphate receptor 1