Therapy-accompanying, quantitative tumor diagnostics with magnetic nanoparticles

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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.