Carmona Asuncion, Roudeau Stéphane, L'Homel Baptiste, Pouzoulet Frédéric, Bonnet-Boissinot Sarah, Prezado Yolanda, Ortega Richard
CNRS, IN2P3, CENBG, UMR 5797, 19 Chemin Du Solarium, 33170 Gradignan, France; University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France.
CNRS, IN2P3, CENBG, UMR 5797, 19 Chemin Du Solarium, 33170 Gradignan, France; University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France.
Anal Biochem. 2017 Apr 15;523:50-57. doi: 10.1016/j.ab.2017.02.010. Epub 2017 Feb 20.
Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging. AGuIX (Activation and Guiding of Irradiation by X-ray) 3 nm particles composed of a polysiloxane network surrounded by gadolinium chelates were used. PIXE results indicate that the direct injection of Gd nanoparticles in tumors results in their heterogeneous diffusion, probably related to variations in tumor density. All tumor regions contain Gd, but with markedly different concentrations, with a more than 250-fold difference. Also Gd can diffuse to the healthy adjacent tissue. This study highlights the usefulness of mapping the distribution of metallic nanoparticles at the intratumoral level, and proposes PIXE as an imaging modality to probe the quantitative distribution of metallic nanoparticles in tumors from experimental animal models with micrometer resolution.
金属纳米粒子作为诊疗药物在癌症放射治疗中具有巨大潜力，因为它们同时可作为医学成像的造影剂和放射治疗增敏剂。与其他抗癌药物一样，肿瘤内扩散是治疗效果的主要限制因素之一。迄今为止，已有一些报告研究了金属纳米粒子在肿瘤内的分布情况。本研究的目的是使用微粒子激发X射线发射（micro-PIXE）成像技术，确定在接种于小鼠体内的U87人胶质母细胞瘤肿瘤内直接注射钆（Gd）纳米粒子后的定量分布。使用了由钆螯合物包围的聚硅氧烷网络组成的AGuIX（X射线激活与引导照射）3纳米粒子。PIXE结果表明，在肿瘤中直接注射Gd纳米粒子会导致其不均匀扩散，这可能与肿瘤密度的变化有关。所有肿瘤区域均含有Gd，但浓度差异显著，相差超过250倍。此外，Gd还可扩散至相邻的健康组织。本研究强调了在肿瘤内水平绘制金属纳米粒子分布图的实用性，并提出将PIXE作为一种成像方式，以微米分辨率探测实验动物模型中肿瘤内金属纳米粒子的定量分布。
