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Advantages of gadolinium based ultrasmall nanoparticles vs molecular gadolinium chelates for radiotherapy guided by MRI for glioma treatment.
Cancer Nanotechnology ( IF 4.5 ) Pub Date : 2014-07-01 , DOI: 10.1186/s12645-014-0004-8
Géraldine Le Duc 1 , Stéphane Roux 2 , Amandine Paruta-Tuarez 3 , Sandrine Dufort 4 , Elke Brauer 1 , Arthur Marais 3 , Charles Truillet 3 , Lucie Sancey 3 , Pascal Perriat 5 , François Lux 3 , Olivier Tillement 3
Affiliation  

AGuIX nanoparticles are formed of a polysiloxane network surrounded by gadolinium chelates. They present several characteristics. They are easy to produce, they present very small hydrodynamic diameters (<5 nm) and they are biodegradable through hydrolysis of siloxane bonds. Such degradation was evaluated in diluted conditions at physiological pH by dynamic light scattering and relaxometry. AGuIX nanoparticles are also known as positive contrast agents and efficient radiosensitizers. The aim of this paper is to compare their efficiency for magnetic resonance imaging and radiosensitization to those of the commercial gadolinium based molecular agent: DOTAREM®. An experiment with healthy animals was conducted and the MRI pictures we obtained show a better contrast with the AguIX compared to the DOTAREM® for the same amount of injected gadolinium in the animal. The better contrast obtained after injection of Aguix than DOTAREM® is due to a higher longitudinal relaxivity and a residential time in the blood circulation that is two times higher. A fast and large increase in the contrast is also observed by MRI after an intravenous injection of the AGuIX in 9 L gliosarcoma bearing rats, and a plateau is reached seven minutes after the injection. We established a radiotherapy protocol consisting of an irradiation by microbeam radiation therapy 20 minutes after the injection of a specific quantity of gadolinium. After microbeam radiation therapy, no notable difference in median survival time was observed in the presence or absence of gadolinium chelates (38 and 44 days respectively). In comparison, the median survival time is increased to 102.5 days with AGuIX particles showing their interest in this nanomedicine protocol. This remarkable radiosensitizing effect could be explained by the persistent tumor uptake of the particles, inducing a significant nanoscale dose deposition under irradiation.

中文翻译:

molecular引导的超小纳米粒子与分子g螯合物相比,在MRI指导下用于神经胶质瘤治疗的放射治疗的优势。

AGuIX纳米颗粒由被siloxane螯合物包围的聚硅氧烷网络形成。它们具有几个特征。它们易于生产,它们的流体动力学直径很小(<5 nm),并且可以通过硅氧烷键的水解而被生物降解。通过动态光散射和弛豫法在生理pH下在稀释条件下评估了这种降解。AGuIX纳米颗粒也被称为正型造影剂和有效的放射增敏剂。本文的目的是将其在磁共振成像和放射增敏方面的效率与市售的基于molecular的分子试剂DOTAREM®进行比较。对健康动物进行了一项实验,在相同数量的动物g中,与DOTAREM®相比,我们获得的MRI图像显示出与AguIX更好的对比度。注射Aguix后获得的对比度比DOTAREM®更好,这是由于较高的纵向松弛度和血液循环中的停留时间高了两倍。静脉注射AGuIX后,在9升患有神经胶质肉瘤的大鼠中,通过MRI还可以观察到造影剂的快速,大幅度增加,并且在注射后7分钟达到了平稳状态。我们建立了一种放射治疗方案,该方案由注射一定量的g后20分钟通过微束放射疗法进行辐照组成。经过微束放射治疗后,在存在或不存在ado螯合物(分别为38天和44天)时,观察到中位生存时间没有显着差异。相比之下,由于AGuIX颗粒显示出他们对这种纳米医学方案的兴趣,中位生存时间增加到102.5天。这种显着的放射增敏作用可以通过颗粒对肿瘤的持续摄取来解释,在辐射下诱导了显着的纳米级剂量沉积。
更新日期:2014-07-01
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