Magnetic nanoparticle monitoring for human cancer therapies

The goal of this project is to develop and provide an imaging modality for the quantitative detection of magnetic nanoparticles (MNP) for the diagnostic support of MNP-based cancer therapies. In these novel treatment approaches, MNP is used to transport medically active substances to the tumor in a targeted way (Magnetic Drug Targeting) or to generate heat for fighting cancer cells in a locally restricted way by means of MNP (magnetic hyperthermia). Thereby, the quantitative imaging detection of the MNP distribution in the human body is essential for the assessment and the individual control of the therapy progress. The method of magnetic relaxometry (MRX) provides a mature measurement technology which has already demonstrated its fundamental suitability for the sensitive and specific detection of MNP in tissue in pre-clinical applications. In this project, the required technology is to be further developed on this basis so that MNP distributions in specific human body regions such as the brain, the prostate, the lymphatic nodes, the gastrointestinal tract, the lungs or the extremities can be quantitatively imaged. Particular attention is given thereby to the establishment of procedures for the prompt demonstration of MNP distributions immediately during, or after the MRX measurements (online monitoring). For this purpose, novel approaches for data processing and for the reconstruction of the distributions with high spatial resolution and, at the same time, with a substantial reduction of the computing time, are to be realized. In addition, approaches for the multi-modal integration of the quantitative MNP distribution and the associated anatomic structure of the body region are to be developed, with the anatomic data being obtained by established procedures such as CT, MRT or laser scanning of the body surface. Another field of activity in this project consists in the investigation of the possibilities of MRX imaging for the demonstration of molecular changes in the body. The MRX signals contain information on the local viscosity in the immediate vicinity of the MNPs. This information can also be imaged and used for the investigation of physiological processes in the body. In the present project, special body-part phantoms, which image the physiological and physical parameters in selected therapy scenarios and which can be loaded in a defined way with MNPs, are to be developed for the evaluation of MRX imaging. These investigations are carried out in close cooperation with our clinical partners to ensure the medical relevance and to take the clinical requirements and the demands on the imaging modality into account from a medical point of view. When the project objectives are achieved, all technical requirements shall be complied with in order to apply MRX imaging of MNPs to new MNP-based cancer therapies in humans.

Magnetic nanoparticles (MNP) promise novel applications for medical diagnostics and therapy. In these novel treatment approaches, nanoparticles are used to deliver therapeutic substances to a target site, e.g. a tumor (magnetic drug targeting), or to generate localized heat to combat cancer cells (magnetic hyperthermia). The quantitative imaging of the particle distribution in the human body is essential for the evaluation and monitoring of the therapy and thus for the safety and efficacy of the treatment. The aim of the research project "quantMRX - Magnetic nanoparticle monitoring for human cancer therapies" was to develop and provide an imaging modality for the quantitative detection of magnetic nanoparticles for the monitoring of MNP-based cancer therapies. Magnetorelaxometry (MRX) is a mature measurement technique for this purpose. Here, the magnetic nanoparticles are aligned by an excitation field and the decay of this magnetization can be measured after the field is switched off. The distribution of the particles can be reconstructed from the relaxation measurement at different sensor positions and with different inhomogeneous excitation fields using mathematical algorithms. The suitability of MRX imaging for the sensitive and specific detection of magnetic nanoparticles in tissue has already been demonstrated in preclinical applications. Building on this, the required technology was further developed in this project so that distributions of magnetic nanoparticles in specific regions of the human body, such as the brain and torso, can be quantitatively imaged. For the necessary enlargement of the field of view to human dimensions, novel optimized excitation coil designs and excitation patterns were developed that enable the imaging of human body parts with an appropriate spatial resolution in the range of a few minutes. In addition, the mathematical algorithms were further developed to consider the non-linear behavior of the particles at higher magnetic field strengths, which are necessary for their detection in large volumes. The novel approaches were implemented in the project both with an established measurement setup using superconducting quantum interference sensors (SQUIDs) cooled with liquid helium and with a novel setup using multi-channel optically pumped magnetometers (OPMs). The latter do not require cooling and are therefore more flexible in terms of positioning. In pilot experiments, the technical feasibility of increasing the imageable volume of MRX imaging was successfully demonstrated for both the size of the human head and the size of the human torso employing specially developed body part phantoms. Furthermore, approaches for the multimodal integration of the quantitative nanoparticle distribution and the associated anatomical structure of the body area under investigation were realized using established methods such as computer tomography or magnetic resonance imaging. This project has laid the technological foundations for the next step of utilizing the developed technology in initial clinical studies.