This Small Business Innovation Research (SBIR) Phase I project addresses a fundamental problem with Magnetic Particle Imaging, a promising, yet new imaging modality. MPI uses magnetic nanoparticles (tracers) to generate a signal that can be used for fast, safe, non-invasive 3D imaging in living patients. The problem relates to the magnetic tracers: there are no existing commercial tracers that are suitable for MPI, due partly to a fundamental lack of control over the physical and magnetic properties of tracers when using existing methods of production. We have addressed this problem by identifying the desired tracer properties for any MPI imaging system and developing a method to produce particles with controlled/tailored properties. The proposed research is designed to further improve the performance of our product, both to fine-tune its physical characteristics and improve its stability in a biological environment. We will improve the stability and performance of our tracer agent by developing a new process for encapsulating the magnetic particles with a biocompatible shell. We will also further improve the performance by developing a novel filtering system to isolate desirable tracers based specifically on their suitability for MPI, as determined by their magnetic relaxation.
The broader impact/commercial potential of this proposed project is an enabling technology for MPI. The goal is to develop a high performance solution that can make clinical MPI commercially viable. MPI using safe iron oxide tracers could reduce patient morbidity during the course of treatment for cardiovascular disease, where current imaging methods like x-ray angiography rely heavily on the use of iodinated contrast media even though they may cause nephrogenic systemic fibrosis in patients, especially those with chronic kidney disease. MPI with targeted tracer probes, also offers significant promise for cancer diagnosis and therapy, with outstanding signal to noise ratio and almost perfect contrast (tissue is diamagnetic and generates no signal in MPI). Finally, the projected commercial impact of MPI is significant: billions of dollars are spent on medical imaging tracers each year, with iodine the most commonly used tracer. Ultimately, MPI, which would circumvent a known hazard in iodine contrast agents, has the potential to generate billions in tracer sales.
This SBIR phase I project supported our efforts to develop a tracer for a new medical imaging technology called Magnetic Particle Imaging. Magnetic Particle Imaging uses safe magnetic fields and safe, iron oxide nanoparticle tracers to visualize blood flow. Magnetic Particle Imaging is an attractive alternative to x-ray or MRI imaging, because it is capable of real-time imaging and it doesn’t use any harmful ionizing radiation (like x-rays). Furthermore, iron oxide nanoparticle tracers are exciting because they are safe for patients with kidney disease, unlike many existing imaging tracers. Currently, more than 30% of heart-disease patients who need medical imaging also have kidney disease and are therefore at risk of complications from existing contrast agents. New tracers like the one we are developing will speed clinical adoption of Magnetic Particle Imaging. Our work addresses the two most critical features needed for a Magnetic Particle Imaging tracer: 1) high-quality magnetic nanocrystals with an average size of 20 to 25 nm diameter, and 2) a biocompatible coating that stabilizes the particles and extends their blood circulation after administration to the patient, by preventing attack from proteins and macrophage cells present in the blood. This SBIR phase I project focused on developing a new biocompatible polymer coating. Our goal was to engineer a coating and coating process that would improve our prototype tracer’s stability and eventually improve circulation time. We chose to use a poly(ethylene glycol) (PEG) coating with silane functional end groups that can bond directly to the iron oxide nanoparticle surface, because PEG is a non-fouling polymer that has been shown to yield good circulation in previous studies. We determined that PEG can be successfully attached to our iron oxide particles using silane chemistry and that the length of the PEG chain and density of the PEG coating impacted the final stability of the nanoparticle tracers. Nanoparticles coated with silane PEG showed good stability in water and in solutions containing blood serum proteins. Based on this initial success, we will next measure how the new PEG coatings impact the blood circulation time of our tracers and whether they can extend the circulation to enable cardiovascular Magnetic Particle Imaging.
