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Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!
Contrast Media & Molecular Imaging Pub Date : 2019-05-29 , DOI: 10.1155/2019/9294586
Min Zhang 1, 2, 3 , Gaëlle Hugon 1, 2 , Caroline Bouillot 4 , Radu Bolbos 4 , Jean-Baptiste Langlois 4 , Thierry Billard 4, 5, 6 , Frédéric Bonnefoi 4 , Biao Li 3 , Luc Zimmer 1, 4, 7 , Fabien Chauveau 1, 2
Affiliation  

The observation that amyloid radiotracers developed for Alzheimer's disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. Ex vivo autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content.

中文翻译:

溶血卵磷脂大鼠局灶性脱髓鞘模型中髓鞘放射示踪剂的评价:谨防陷阱!

为阿尔茨海默氏病开发的淀粉样放射性示踪剂与脑白质结合的观察结果为多发性硬化中髓磷脂的核显像铺平了道路。溶血卵磷脂(溶血磷脂酰胆碱(LPC))大鼠脱髓鞘模型被证明可用于评估和比较候选放射性示踪剂与靶髓磷脂。立体定向LPC注射后的局灶性脱髓鞘作用大于在实验性自身免疫性脑炎模型中观察到的病变,然后进行自发进行性髓鞘再生。此外,对侧半球可以作为给定动物的内部对照。然而,脱髓鞘可伴有局灶性坏死和/或邻近的心室扩张。这些副作用对影像学表现的影响从未得到仔细评估。本研究描述了LPC模型的优化,并强调了使用MRI控制模型的变异性和缺陷。典型的淀粉样蛋白示踪剂[11C] PIB用于显示体内PET不能提供足够的敏感性来可靠地跟踪髓磷脂的变化,并且可能对LPC副作用而不是脱髓鞘如此敏感。为了充分评估和比较放射性示踪剂,以评估髓磷脂的含量,应首选使用氟放射性示踪剂的体外放射自显影。典型的淀粉样蛋白示踪剂[11C] PIB用于显示体内PET不能提供足够的敏感性来可靠地跟踪髓磷脂的变化,并且可能对LPC副作用而不是脱髓鞘如此敏感。为了充分评估和比较放射性示踪剂以评估髓磷脂的含量,应首选使用氟放射性示踪剂的体外放射自显影。典型的淀粉样蛋白示踪剂[11C] PIB用于显示体内PET不能提供足够的敏感性来可靠地跟踪髓磷脂的变化,并且可能对LPC副作用而不是脱髓鞘如此敏感。为了充分评估和比较放射性示踪剂以评估髓磷脂的含量,应首选使用氟放射性示踪剂的体外放射自显影。
更新日期:2019-11-01
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