Evaluation of PEG-coated iron oxide nanoparticles as blood pool tracers for preclinical magnetic particle imaging

Abstract

Superparamagnetic iron oxide (SPIO) nanoparticles with optimized and well-characterized properties are critical for Magnetic Particle Imaging (MPI). MPI is a novel in vivo imaging modality that promises to integrate the speed of CT, safety of MRI and sensitivity of PET. Since SPIOs are the source of MPI signal, both the core and surface properties must be optimized to enable efficient in vivo imaging with pharmacokinetics tailored for specific imaging applications. Existing SPIOs like Resovist (ferucarbotran) provide suboptimal MPI signal, and further limit MPI's in vivo utility due to rapid systemic clearance. An SPIO agent with a long blood half-life (t1/2) would be a versatile MPI tracer with widespread applications. Here we show a long circulating polyethylene glycol (PEG)-coated SPIO tracer, LS-008, provides excellent colloidal stability and persistent intravascular MPI signal, showing potential as the first blood pool tracer optimized for MPI. We evaluated variations of the PEG coating and found that colloidal stability of tracers improved with increasing PEG molecular weight (keeping PEG loading constant). Blood circulation in mice, evaluated using Magnetic Particle Spectrometry (MPS), showed that t1/2 of SPIO tracers varied with both PEG molecular weight and loading. LS-008, coated with 20 kDa PEG at 18.8% loading capacity, provided the most promising long-term colloidal stability with a t1/2 of about 105 minutes in mice. In vivo MPI imaging with LS-008 in a 7 T/m/μ0 3D x-space MPI mouse scanner revealed a prolonged intravascular signal (3-5 hours) post-injection. Our results show the optimized magnetic properties a nd long systemic retention of LS-008 make it a promising blood pool MPI tracer, with potential to enable MPI imaging in cardio - and cerebrovascular disease models, and solid tumor quantification and imaging via enhanced permeation and retention.

Magnetic particle imaging of islet transplantation in the liver and under the kidney capsule in mouse models

“…Magnetic particle imaging (MPI) is an emerging tracer imaging modality that directly images the magnetization of iron oxide nanoparticles (15), and is specific, sensitive, linearly quantitative, and translatable. MPI has already been utilized for tumor imaging (16), lymph node staging (17), cell tracking (18)(19)(20)(21), vascular imaging (22), pulmonary embolism detection using ventilation/perfusion (23), traumatic brain injury (24), and other indications. The technique visualizes the nanoparticle distribution in the sample, and the images can be acquired as both a two-dimensional (2D) projection image (akin to X-ray), as well as in a 3D tomographic image (akin to X-ray CT) (18,(25)(26)(27)(28).…”

Tomographic magnetic particle imaging of cancer targeted nanoparticles

“…18 In the x-space MPI image reconstruction method, improvements in image quality can be represented by narrower full width at half maximum (FWHM) and larger peak heights of nanoparticles d m /d H, measured by a magnetic particle spectrometer (MPS). 6, 19–21 Here, we use thermodynamically phase-pure and monodisperse nanoparticles ( d C ~ 25–27nm), with near ideal saturation magnetization, 22 and long blood circulation times, 11 optimized for cancer diagnosis using MPI (Figs. 1 and S3).…”

Seeing SPIOs Directly In Vivo with Magnetic Particle Imaging

“…2c–d). The ability to image dynamics without tissue background signal in MPI may also make it well-suited for applications in assessing functional brain physiology using optimized long-circulating SPIO tracers [21, 45]. …”

“…For groups interested in developing MPI technology, challenges include (a) improving the spatial resolution of MPI, which is determined by SPIO tracer size and composition, applied magnetic fields, and SPIO relaxation times [47, 48]; (b) improving the detection sensitivity in MPI; (c) robust multi-color imaging [49, 50]; (d) theranostic MPI for guidance and real-time feedback on hyperthermia heating [51–53] (e) improving tracer circulation time and image contrast [21, 45, 54] ; (f) optimal combination of MPI with anatomic imaging modalities like CT or MRI for multi-modal imaging; (g) targeting SPIOs with great specificity to pathophysiology including cancer, cardiovascular disease, stroke; and (h) scaling up preclinical MPI hardware to human MPI, while observing FDA and EU biosafety restrictions, including peripheral nerve stimulation (PNS) and tissue heating Specific Absorption Rate (SAR) limits [27, 29] . These areas are the focus of the activities of the MPI interest group.…”