PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB
PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB
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DOI：
10.1007/s00259-013-2682-6
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发表时间：
2014-05-01
影响因子：
9.1
通讯作者：
de Vries, Erik F. J.
中科院分区：
文献类型：
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作者：
Faria, Daniele de Paula;Copray, Sjef;de Vries, Erik F. J.
在这项研究中，我们比较了[C-11]CIC，[C-11]MeDAS和[C-11]PIB揭示多发性硬化症大鼠模型中局灶性病变中髓鞘含量的时间变化的能力。Sprague-Dawley大鼠被立体定向注射1%溶血素或盐水到右脑半球的胼胝体和纹状体中。分别于注射生理盐水后7 d（对照组）、注射溶血素后7 d（脱髓鞘组）和注射溶血素后4周（再髓鞘组）行PET动态显像，[C-11]CIC、[C-11]MeDAS和[C-11]PIB的动力学与Logan图解法拟合最好，表明示踪剂结合是可逆的。commonly建模显示，所有示踪剂最适合与可逆的两个组织房室模型。病灶内示踪剂的摄取和分布量与髓鞘状态一致。然而，[C-11]CIC的缓慢动力学和均匀脑摄取使得该示踪剂不太适合于体内PET成像。[C-11]PIB在大脑的白色物质中显示出良好的摄取，但[C-11]PIB在小脑中的摄取较低，尽管该区域的髓鞘密度较高。[C-11]MeDAS分布与不同脑区的髓鞘密度相关性良好。本研究表明，PET成像局灶性病变的脱髓鞘和髓鞘再生过程是可行的。我们对三种髓鞘示踪剂的比较表明，[C-11]MeDAS对整个CNS的脱髓鞘和髓鞘再生病变的定量PET成像具有比[C-11]CIC和[C-11]PIB更有利的性质。
In this study, we compared the ability of [C-11]CIC, [C-11]MeDAS and [C-11]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake.Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group).The kinetics of [C-11]CIC, [C-11]MeDAS and [C-11]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [C-11]CIC make this tracer less suitable for in vivo PET imaging. [C-11]PIB showed good uptake in the white matter in the cerebrum, but [C-11]PIB uptake in the cerebellum was low, despite high myelin density in this region. [C-11]MeDAS distribution correlated well with myelin density in different brain regions.This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [C-11]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [C-11]CIC and [C-11]PIB.