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

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Abstract

Purpose

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.

Procedures

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.

Results

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.

Conclusions

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.

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Abbreviations

3D-OSEM:

Three-dimensional ordered subset expectation maximization

BDNF:

Brain-derived neurotrophic factor

CCL2:

Chemokine (C-C motif) ligand 2

CFA:

Complete Freund’s adjuvant

CNS:

Central nervous system

DAB:

3,3-Diaminobenzidine

EAE:

Experimental autoimmune encephalomyelitis

GDNF:

Glial cell-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

HPLC:

High-performance liquid chromatography

HRP:

Horseradish peroxidase

Iba-1:

Ionized calcium-binding adapter molecule 1

IL:

Interleukin

MBP:

Myelin basic protein

MS:

Multiple sclerosis

PBS:

Phosphate-buffered saline

PET:

Positron emission tomography

S1PR1:

Sphingosine-1-phosphate receptor 1

SUV:

Standardized uptake value

TAC:

Time–activity curve

TNF-α:

Tumor necrosis factor-α

TSPO:

Translocator protein 18 kDa

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Acknowledgments

This work was supported by DOE-Training in Techniques and Translation: Novel Nuclear Medicine Imaging Agents for Oncology and Neurology, DESC0008432, the Washington University School of Medicine Mallinckrodt Institute of Radiology (MIR) Cyclotron Facility Allotment #14-017, and NIH/NINDS, NS075527, and NIH/NIMH, MH092797. We thank Nicole Fettig, Margaret Morris, Amanda Roth, Lori Strong, and Ann Stroncek for their assistance with the microPET imaging studies, Marlene Scott and Bill Coleman in the Elvie L. Taylor Histology Core Facility of Washington University School of Medicine for sample embedding and H&E staining. The authors also like to thank Lynne A. Jones’ assistance in preparation of the manuscript.

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Authors and Affiliations

  1. Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Hui Liu, Hongjun Jin, Xuyi Yue, Zonghua Luo, Chunling Liu, Adam J. Rosenberg & Zhude Tu

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  1. Hui Liu
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  2. Hongjun Jin
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Correspondence to Zhude Tu.

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Liu, H., Jin, H., Yue, X. et al. PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis. Mol Imaging Biol 18, 724–732 (2016). https://doi.org/10.1007/s11307-016-0944-y

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