LS-008

Optimizing tracers for individual imaging techniques is an active field of research. The purpose of this study was to perform in vitro and in vivo magnetic particle imaging (MPI) measurements using a new monodisperse and size-optimized tracer, LS-008, and to compare it with the performance of Resovist, the standard MPI tracer. Magnetic particle spectroscopy (MPS) and in vitro MPI measurements were performed in concerns of concentration and amount of tracer in a phantom. In vivo studies were carried out in healthy FVB mice. The first group (n  =  3) received 60 µl LS-008 (87 mM) and the second (n  =  3) diluted Resovist of the same concentration and volume. Tracer injections were performed with a syringe pump during a dynamic MPI scan. For anatomic referencing MRI was applied beforehand of the MPI measurements. Summing up MPS examinations and in vitro MPI experiments, LS-008 showed better sensitivity and spatial resolution than Resovist. In vivo both tracers can visualize the propagation of the bolus through the inferior vena cava. MPI with LS-008 did show less temporal fluctuation artifacts and the pulsation of blood due to respiratory and cardiac cycle was detectable. With LS-008 the aorta was distinguishable from the caval vein while with Resovist this failed. A liver vessel and a vessel structure leading cranially could only be observed with LS-008 and not with Resovist. Beside these structural advantages both tracers showed very different blood half-life. For LS-008 we found 88 min. Resovist did show a fast liver accumulation and a half-life of 13 min. Only with LS-008 the perfusion fraction in liver and kidney was measureable. MPI for angiography can be significantly improved by applying more effective tracers. LS-008 shows a clear improvement concerning the delineation while resolving a larger number of vessels in comparison to Resovist. Therefore, in aspects of quality and quantity LS-008 is clearly favorable for angiographic and perfusion studies.

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 X-ray 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 a 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 (t_1/2) would be a versatile MPI tracer with widespread applications. Here we show that a long circulating polyethylene glycol (PEG)-coated SPIO tracer, LS-008, provides excellent colloidal stability and a persistent intravascular MPI signal, showing its potential as the first blood pool tracer optimized for MPI. We evaluated variations of PEG coating and found that colloidal stability of tracers improved with the increasing PEG molecular weight (keeping PEG loading constant). Blood circulation in mice, evaluated using Magnetic Particle Spectrometry (MPS), showed that the t_1/2 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 t_1/2 of about 105 minutes in mice. In vivo MPI imaging with LS-008 using 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 and long systemic retention of LS-008 making 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.