Therapy-accompanying, quantitative tumor diagnostics with magnetic nanoparticles

使用磁性纳米颗粒进行伴随治疗的定量肿瘤诊断

• 批准号: 299175995
• 负责人: Professor Dr. Christoph Alexiou
• 金额: --
• 依托单位: Hals-Nasen-Ohren-Klinik, Kopf- und Halschirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/299175995?language=en
• 关键词: Therapy; accompanying; quantitative; tumor; diagnostics

Magnetic Particle Imaging (MPI) is a new imaging technique utilizing magnetic nanoparticles as contrast agents to generate images with a high spatiotemporal resolution. It also offers the possibility of simultaneous quantification of the amount of nanoparticles in the field of view. Being very promising drug carriers, magnetic nanoparticles are in the focus of nanomedical research. In cancer therapy, Magnetic Drug Targeting (MDT) combines intraarterial application of nanocarriers and their accumulation in the tumor area by an external magnetic field. Consequently, high local doses of the chemotherapeutic can be achieved. Combining the concepts of MPI and MDT offers the unique opportunity of imaging of the particle distribution in the diseased area, but also the quantification of nanoparticle amount with a resolution much higher than achieved with magnetrelaxometry (MRX). Combination of these techniques would thus allow direct monitoring of drug distribution in the tumor area after administration, which would facilitate the decision-making with regard to the necessity of further administrations and enable the assessment of the therapy (imaging controlled therapy). In the framework of the Major-Equipment-Initiative of the DFG, one of the MPI-Scanners was installed at the Charité/PTB in Berlin in 2014. Thanks to the long-lasting and close cooperation between the Section for Experimental Oncology and Nanomedicine (SEON) at the University Hospital Erlangen and the working groups Trahms/Wiekhorst (PTB, Berlin) and Dutz (TU-Ilmenau), it is now possible to implement and further develop this concept in a preclinical setting. The aim of the project is to investigate the imaging properties of the nanoparticles developed at SEON. Then, these nanoparticles will be modified in order to provide theranostic agents that retain their very good therapeutic properties and acquire optimal diagnostic properties, allowing the monitoring of accumulation and distribution of the nanoparticles in a tumor area. Additionally, the performance of the nanoparticles in magnetic resonance imaging (MRI) and MPI will be compared. We will start the investigations with two nanoparticle systems synthesized at SEON (SEONLA-BSA and SEONDEX). These particles have been shown to have outstanding physicochemical properties, blood stability and biocompatibility. The imaging properties of these basic systems will be determined using MRI and MPI/MPS (collab. Trahms/Wiekhorst). Subsequently, certain synthesis parameters will be modified and their influence on imaging and therapeutically-relevant properties will be investigated in vitro and in phantoms produced by the working group Dutz. Subsequently, the best batches will be tested in vivo, by imaging their accumulation in the livers of small animals (rats). Finally, we will attempt to translate the results of those experiments to imaging and measuring the accumulation of the nanoparticles in experimental in the liver of rats.

磁粒子成像（MPI）是一种利用磁性纳米粒子作为造影剂来产生具有高时空分辨率的图像的新成像技术。它还提供了同时量化视野中纳米颗粒数量的可能性。磁性纳米粒子作为一种很有前途的药物载体，是纳米医学研究的热点。在癌症治疗中，磁性药物靶向（MDT）结合了纳米载体的动脉内应用及其通过外部磁场在肿瘤区域中的积累。因此，可以实现高局部剂量的化疗剂。结合MPI和MDT的概念提供了对患病区域中的颗粒分布进行成像的独特机会，而且还提供了比磁弛豫法（MRX）所实现的分辨率高得多的纳米颗粒量的定量。因此，这些技术的组合将允许在给药后直接监测肿瘤区域中的药物分布，这将有助于关于进一步给药的必要性的决策，并能够评估治疗（成像控制治疗）。在DFG的主要设备倡议框架内，2014年在柏林的Charité/PTB安装了一台MPI扫描仪。由于埃尔兰根大学医院实验肿瘤学和纳米医学科（SEON）与Trahms/Wiekhorst（PTB，柏林）和Dutz（TU-Ilmenau）工作组之间的长期密切合作，现在可以在临床前环境中实施和进一步发展这一概念。该项目的目的是研究SEON开发的纳米颗粒的成像特性。然后，这些纳米颗粒将被修饰，以提供保留其非常好的治疗特性并获得最佳诊断特性的治疗诊断剂，从而允许监测纳米颗粒在肿瘤区域中的积累和分布。此外，将比较纳米颗粒在磁共振成像（MRI）和MPI中的性能。我们将从SEON合成的两种纳米颗粒系统（SEONLA-BSA和SEONDEX）开始研究。这些颗粒已被证明具有出色的物理化学性质，血液稳定性和生物相容性。将使用MRI和MPI/MPS（collab. Trahms/Wiekhorst）。随后，将修改某些合成参数，并在体外和Dutz工作组生产的模型中研究它们对成像和治疗相关特性的影响。随后，将通过成像其在小动物（大鼠）肝脏中的蓄积，对最佳批次进行体内检测。最后，我们将尝试将这些实验的结果转化为成像和测量实验大鼠肝脏中纳米颗粒的积累。