The AGuIX® (NH TherAguix) nanoparticle has been developed to enhance radiotherapy treatment and provide strong MR contrast. These two properties have previously been investigated separately and progressed to clinical trial following a clinical workflow of separate MR imaging followed some time later by radiotherapy treatment. The recent development of MRI-linacs (combined Magnetic Resonance Imaging–linear accelerator systems enabling MRI-guided radiotherapy) opens up a new workflow where MR confirmation of nanoparticle uptake can be carried out at the time of treatment. A preclinical study was carried out to assess the suitability of a gadolinium-containing nanoparticle AGuIX® (NH TherAguix) for nano-enhanced image-guided radiotherapy on an MRI-linac. Treatments were carried out on F344 Fischer rats bearing a 9L glioma brain tumour. Animals received either: (A) no treatment; (B) injection of nanoparticles followed by MRI; (C) radiotherapy with MRI; or (D) injection of nanoparticles followed by radiotherapy with MRI. Pre-clinical irradiations were carried out on the 1.0 T, 6 MV in-line Australian MRI-linac. Imaging used a custom head coil specially designed to minimise interference from the radiotherapy beam. Anaesthetised rats were not restrained during treatment but were monitored with a cine-MRI sequence. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was used to quantify residual gadolinium in the brain in normal and tumour tissue. A preclinical evaluation of nano-enhanced radiation treatment has been carried out on a 1.0 T MRI-linac, establishing a workflow on these novel systems. Extension of life when combining radiotherapy with nanoparticles was not statistically different from that for rats receiving radiotherapy only. However, there was no detrimental effect for animals receiving nanoparticles and radiation treatment in the magnetic field compared with control branches. Cine-MR imaging was sufficient to carry out monitoring of anaesthetised animals during treatment. AGuIX nanoparticles demonstrated good positive contrast on the MRI-linac system allowing confirmation of tumour extent and nanoparticle uptake at the time of treatment. Novel nano-enhanced radiotherapy with gadolinium-containing nanoparticles is ideally suited for implementation on an MRI-linac, allowing a workflow with time-of-treatment imaging. Live irradiations using this treatment workflow, carried out for the first time at the Australian MRI-linac, confirm the safety and feasibility of performing MRI-guided radiotherapy with AGuIX® nanoparticles. Follow-up studies are needed to demonstrate on an MRI-linac the radiation enhancement effects previously shown with conventional radiotherapy.

中文翻译：

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g基纳米颗粒增强的MRI指导的放射治疗：MRI直线加速器的临床前评估

已经开发了AGuIX®（NH TherAguix）纳米颗粒，以增强放射治疗效果并提供强MR对比。先前已经分别研究了这两种特性，并在单独的MR成像的临床工作流程之后进行了临床试验，随后又进行了放射治疗。MRI-直线加速器（磁共振成像-线性加速器系统结合了MRI引导的放射疗法）的最新发展开辟了一个新的工作流程，可以在治疗时进行MR确认纳米颗粒的摄取。开展了临床前研究，以评估含a纳米颗粒（NH TherAguix）对MRI直线加速器进行纳米增强图像引导放射治疗的适用性。对患有9L胶质瘤脑瘤的F344费歇尔大鼠进行治疗。动物接受以下任何一种治疗：（A）不治疗；（B）注射纳米颗粒，然后进行MRI；（三）MRI放疗；（D）注射纳米粒子，然后进行MRI放射治疗。在1.0 T，6 MV在线澳大利亚MRI直线加速器上进行临床前照射。成像使用专门设计的定制头线圈，以最大程度地减少放射治疗束的干扰。麻醉的大鼠在治疗过程中不受约束，但通过电影-MRI序列进行监测。电感耦合等离子体质谱（ICP-MS）分析用于量化正常组织和肿瘤组织中大脑中残留的g。在1.0 T MRI直线加速器上进行了纳米增强放射治疗的临床前评估，从而在这些新型系统上建立了工作流程。与仅接受放射治疗的大鼠相比，将放射治疗与纳米颗粒联合使用可延长寿命。但是，与对照组相比，在磁场中接受纳米颗粒和放射治疗的动物没有有害作用。Cine-MR成像足以在治疗过程中进行麻醉动物的监测。AGuIX纳米颗粒在MRI-直线加速器系统上显示出良好的正反差，从而可以在治疗时确认肿瘤程度和纳米颗粒的摄取。使用含g纳米颗粒的新型纳米增强放射疗法非常适合在MRI直线加速器上实施，从而实现了带有治疗时间成像的工作流程。使用这种治疗工作流程进行的实时辐射是在澳大利亚MRI直线加速器上首次进行的，确认使用AGuIX®纳米粒子进行MRI引导的放射治疗的安全性和可行性。需要进行后续研究，以在MRI直线加速器上证明以前用传统放射疗法显示出的放射增强作用。