title: 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 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 (t1/2) 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 t1/2of 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 t1/2of about 105 minutes in mice. In vivo MPI imaging with LS-008 using a 7 T/m/μ03D 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.
authors.affiliation: LodeSpin Labs, Seattle, WA 98195, USA. amit@lodespin.com.
authors.forename: A P
authors.identifier: http://orcid.org/0000-0003-4049-1855
authors.initials: AP
authors.lastname: Khandhar
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: P
authors.initials: P
authors.lastname: Keselman
authors.affiliation: LodeSpin Labs, Seattle, WA 98195, USA. amit@lodespin.com.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kemp
authors.affiliation: LodeSpin Labs, Seattle, WA 98195, USA. amit@lodespin.com.
authors.forename: R M
authors.identifier: http://orcid.org/0000-0003-3338-1041
authors.initials: RM
authors.lastname: Ferguson
authors.affiliation: Magnetic Insight, Inc., Alameda, CA 94501, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Goodwill
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Conolly
authors.affiliation: Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA. kannanmk@uw.edu.
authors.forename: K M
authors.initials: KM
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D005290:Ferric Compounds; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011092:Polyethylene Glycols