[C]PIB PET 成像可以检测到进行性多发性硬化症非人灵长类动物模型中的白质和灰质脱髓鞘。
[C]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis.
机构信息
Laboratory of Nuclear Medicine (LIM-43), Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Department of Physiology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
出版信息
Mult Scler Relat Disord. 2019 Oct;35:108-115. doi: 10.1016/j.msard.2019.07.020. Epub 2019 Jul 24.
BACKGROUND
Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C]PIB is widely used for detection of β-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS.
METHODS
Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of recombinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis.
RESULTS
All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r= 0.32, P < 0.0001) and the rhMOG/CFA group (r= 0.46, P < 0.0001).
CONCLUSION
[C]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.
背景
多发性硬化症（MS）是一种中枢神经系统脱髓鞘和炎症性疾病。其诊断基于临床，通常通过磁共振成像（MRI）确认。然而，这种影像学方式并不理想，无法区分灰白质区域的脱髓鞘与炎症性病变。正电子发射断层扫描（PET）利用特定放射性药物，可作为一种区分这些过程的工具。放射性药物[C]PIB 广泛用于检测β-淀粉样斑块，但由于其在白质中的一致摄取，也被用于分析髓鞘含量。本研究旨在评估[C]PIB PET 成像作为一种工具，用于检测非人类灵长类动物进展性 MS 模型中白质和灰质内脱髓鞘区域。
方法
通过注射重组人髓鞘少突胶质细胞糖蛋白（rhMOG）在不完全弗氏佐剂（IFA）或完全弗氏佐剂（CFA）中乳化，在狨猴中诱导实验性自身免疫性脑脊髓炎（EAE）。在免疫前（基线）和出现症状后（实验结束时）采集[C]PIB PET 图像。分离脑组织进行组织化学分析。
结果
所有 rhMOG/IFA 治疗和 rhMOG/CFA 治疗的动物均出现 EAE 的临床症状。rhMOG/CFA 组仅在左侧运动皮层（9%，P=0.011）观察到[C]PIB 摄取减少。对于 rhMOG/IFA 组，全脑（15%，P=0.015）、胼胝体体部右侧（34%，P=0.02）、胼胝体压部（38%，P=0.004）、海马（19%，P=0.036）、视束（13%，P=0.025）、丘脑（14%，P=0.041）、苍白球（23%，P=0.017）、尾状核头部（25%，P=0.045）、尾状核尾部（29%，P=0.003）、壳核（28%，P=0.047）和胼胝体体部左侧（14%，P=0.037）及尾状核头部（23%，P=0.023）观察到[C]PIB 摄取显著减少。[C]PIB 摄取与卢索快速蓝组织学（髓鞘标志物）显著相关，在 rhMOG/IFA 组（r=0.32，P<0.0001）和 rhMOG/CFA 组（r=0.46，P<0.0001）中均如此。
结论
[C]PIB PET 成像可有效检测非人类灵长类动物进展性 MS 模型中灰质和白质的脱髓鞘。
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