(708a) Optimizing Superparamagnetic Iron Oxide Nanoparticle Synthesis and Peg Coating for Magnetic Particle Imaging Performance and Long Blood Circulation Half Life

Magnetic particle imaging (MPI) is a novel biomedical imaging modality that allows non-invasive, tomographic, and quantitative tracking of the distribution of superparamagnetic iron oxide nanoparticle (SPION) tracers through their nonlinear dynamic magnetization response to an alternating excitation field. As MPI directly detects SPIONs, the resolution and sensitivity of MPI is primarily impacted by the magnetic response of the nanoparticle tracers. Importantly, the physics of signal generation in MPI are distinct from that in Magnetic Resonance Imaging (MRI). As such, SPION tracers developed for MRI are not necessarily ideal for MPI. In addition, surface modification and formulation are also important factors that affect application performance. For example, there are several applications that would benefit from long blood circulation time, such as in blood pool imaging, evaluating traumatic brain injury, gut bleed detection, and functional MPI. These considerations suggest a need for developing SPIONs with physicochemical and magnetic properties that are tailored for specific MPI applications.

Ferucarbotran (Resovist^®), a commercially available SPION contrast agent developed specifically for MRI is commonly used for MPI studies. It has been suggested that only 3% of the total iron mass in these tracers contributes to their MPI signal. Another commercially available tracer is Synomag-D^®, an aqueous suspension of multi-core maghemite nanoparticles covered by a dextran shell with PEG-OMe on the surface. The MPI performance of Synomag-D^® has been evaluated using a magnetic particle spectrometer and results suggest better performance compared to Resovist^®. However, studies evaluating its in vivo performance are lacking. LS-008, a tailored tracer developed for MPI with high resolution was evaluated to have blood half-life of 105 min in mice. However, LS-008 tracers are no longer available and suitable alternatives that combine resolution with long circulation time are lacking. Furthermore, while these tracers are widely tested using prototype MPI scanners and with the Bruker pre-clinical MPI scanner, their performance has not been evaluated in the newer MOMENTUM^TM pre-clinical scanner. Because SPION performance varies with the different scanner construction parameters, such as the amplitude and frequency of the applied magnetic field and the magnitude of the field gradient, the MPI performance of a given tracer can vary from different type of scanners. The growing adoption of the MOMENTUM^TM MPI scanner suggests that comparative performance studies of MPI tracers using this scanner would be of value to the community.

Here, we will discuss the physics of signal generation in MPI and how they inform optimization of SPION synthesis for sensitivity and resolution in MPI. We will also discuss the requirements on particle surface coating and colloidal stability imposed by applications of MPI to blood pool imaging. Experimental results will be presented for single-core SPION MPI tracers obtained using a semi-batch thermal decomposition synthesis with controlled addition of molecular oxygen, followed by an optimized PEG-silane ligand exchange procedure. Results will show how MPI performance relates to thermal decomposition synthesis conditions and intrinsic magnetic properties of the SPIONs. The physical and magnetic properties, MPI performance, and blood circulation time of these tracers will be compared to those of the two commercially available SPIONs: ferucarbotran and PEG-coated Synomag^®-D. The optimized tracers have better MPI sensitivity and much longer circulation half-life than both commercial tracers, making them ideal for use as blood pool imaging tracer in MPI.