Therapy-accompanying, quantitative tumor diagnostics with magnetic nanoparticles

磁粒子成像(MPI)是一种利用磁性纳米粒子作为造影剂来生成高时空分辨率图像的新技术。它还提供了同时量化视野中纳米颗粒数量的可能性。磁性纳米颗粒作为一种非常有前途的药物载体，是纳米医学研究的热点。在癌症治疗中，磁性药物靶向(MDT)结合了纳米载体在动脉内的应用和它们在外磁场作用下在肿瘤区域的聚集。因此，可以实现高局部剂量的化疗。结合MPI和MDT的概念，不仅为成像病变区域的颗粒分布提供了独特的机会，而且还提供了纳米颗粒数量的量化，其分辨率远远高于磁弛豫法(MRX)。因此，这些技术的结合将允许在给药后直接监测肿瘤区域的药物分布，这将有助于关于进一步给药的必要性的决策，并使对治疗(成像控制治疗)的评估成为可能。在德国总工会主要装备倡议的框架内，2014年在柏林的Charité/PTB安装了一台MPI扫描仪。由于Erlangen大学医院实验肿瘤学和纳米医学科(SEON)与TRAHMS/Wiekhorst(柏林PTB)和DUZ(TU-Ilmenau)工作组之间长期密切的合作，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在SEON开发的纳米粒子的成像特性。然后，这些纳米颗粒将被修饰，以提供保持其非常好的治疗特性并获得最佳诊断特性的治疗药物，从而允许监测纳米颗粒在肿瘤区域的积累和分布。此外，还将比较纳米粒子在磁共振成像(MRI)和MPI中的性能。我们将从SEON合成的两个纳米粒子系统(SEONLA-BSA和SEONDEX)开始研究。这些微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。这些基本系统的成像特性将使用MRI和MPI/MPS(协作.Trahms/Wiekhorst)。随后，某些合成参数将被修改，它们对成像和治疗相关特性的影响将在体外和Duz工作组生产的模体中进行调查。随后，将对最好的批次进行活体测试，通过成像它们在小动物(大鼠)的肝脏中积累。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中纳米颗粒在大鼠肝脏中的积聚。

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.