多发性硬化大鼠模型中S1PR1表达的正电子发射断层显像（PET）研究
PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis.
作者信息
Liu Hui, Jin Hongjun, Yue Xuyi, Luo Zonghua, Liu Chunling, Rosenberg Adam J, Tu Zhude
机构信息
Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
出版信息
Mol Imaging Biol. 2016 Oct;18(5):724-32. doi: 10.1007/s11307-016-0944-y.
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 [(11)C]TZ3321.
PROCEDURES
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.
RESULTS
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.
CONCLUSIONS
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.
目的
多发性硬化症（MS）病灶中鞘氨醇-1-磷酸受体1（S1PR1）表达上调与神经炎症反应相关。本研究使用S1PR1正电子发射断层扫描（PET）放射性示踪剂[(11)C]TZ3321，调查实验性自身免疫性脑脊髓炎（EAE）大鼠模型（一种MS模型）脊髓中神经炎症与S1PR1表达之间的相关性。
程序
进行[(11)C]TZ3321的微型PET成像研究，以测量[(11)C]TZ3321在EAE大鼠脊髓中的摄取情况。进行免疫组织化学染色以确认S1PR1和其他炎症生物标志物的过表达。
结果
微型PET成像显示，注射后35 - 60分钟，EAE大鼠腰段脊髓中[(11)C]TZ3321的摄取量比假手术对照组增加了20 - 30%。[(11)C]TZ3321摄取量的增加与EAE大鼠腰段脊髓中S1PR1的过表达相关，这一点通过免疫组织化学染色得到证实。S1PR1表达上调与胶质细胞活化和免疫细胞浸润有关。
结论
使用特异性放射性配体[(11)C]TZ3321的微型PET成像方式能够评估EAE大鼠腰段脊髓中S1PR1的表达。这可能为评估MS和其他炎症性疾病中的神经炎症反应提供一种新方法。
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