Ultrasound methods for quantitative imaging of the distribution of magnetic nanoparticles in biological tissue in connection with drug delivery concepts and magnetic hyperthermia for localized tumor treatment

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Nanoparticles are of great interest in medical diagnostics and therapy. Because of the small size of single nanoparticles, the so-called EPR effect (Enhanced Permeability and Retention) can be used which allows, after their administration via blood vessels, a strong penetration from the vessels into biological tissue and an intensive impact on the tissue. This applies in particular to tumor tissue since its vascular pores are often enlarged.Magnetic nanoparticles can be moved, spatially accumulated and heated by magnetic fields, which makes them interesting for tumor therapy. The planned project involves two methods: (a) localized chemotherapy, in which drug-carrying magnetic nanoparticles are locally accumulated in the tumor tissue from outside the body using an electromagnet and can in this way release the drugs in the tumor tissue area. This procedure, which reduces the side effects of conventional chemotherapy, is known as Magnetic Drug Targeting (MDT). In the second method, (b) Magnetic Hyperthermia (MH), the particles are heated using an alternating magnetic field and act thermally on the tissue.In both cases, there is a need to monitor the spatial distribution of the particles in the tissue areas to be treated and to quantitatively determine the particle density. Although Magnetic Resonance Imaging (MRI) and Magnetic Particle Imaging (MPI) are suitable in principle for this, these modalities are complex and difficult to apply in the MDT and MH therapy methods. In contrast, ultrasound is known to be a less complex and easy-to-use modality. However, due to their small sizes, nanoparticles only generate extremely weak backscatter in ultrasound and are not visible in conventional ultrasound images. Therefore, special effects have to be utilized for a sonographic detection and visualization of the nanoparticles.In the "magneto-motive" approach, the nanoparticles are stimulated by alternating magnetic fields to perform periodic movements that are transferred to the surrounding biological tissue, making the particle movements indirectly visible with ultrasound and particle distributions qualitatively displayed. An inverse concept also allows a quantitative determination of the particle density. A second approach takes advantage of the fact that the tissue penetrated by nanoparticles changes the bulk mechanical, e.g., elastic properties. The particle density can thus be visualized and quantified using ultrasound elastography. Based on the encouraging results of our own preliminary work, these procedures are to be further developed and investigated as part of the therapy procedures described. At the same time, the chance is examined to influence the representation and quantifiability of the particles by modifying the nanoparticle synthesis. The investigations shall initially be carried out on phantoms and later in animal experiments.