title: In vivo multimodal magnetic particle imaging (MPI) with tailored magneto/optical contrast agents.
abstract: Magnetic Particle Imaging (MPI) is a novel non-invasive biomedical imaging modality that uses safe magnetite nanoparticles as tracers. Controlled synthesis of iron oxide nanoparticles (NPs) with tuned size-dependent magnetic relaxation properties is critical for the development of MPI. Additional functionalization of these NPs for other imaging modalities (e.g. MRI and fluorescent imaging) would accelerate screening of the MPI tracers based on their in vitro and in vivo performance in pre-clinical trials. Here, we conjugated two different types of poly-ethylene-glycols (NH2-PEG-NH2 and NH2-PEG-FMOC) to monodisperse carboxylated 19.7 nm NPs by amide bonding. Further, we labeled these NPs with Cy5.5 near infra-red fluorescent (NIRF) molecules. Bi-functional PEG (NH2-PEG-NH2) resulted in larger hydrodynamic size (∼98 nm vs. ∼43 nm) of the tracers, due to inter-particle crosslinking. Formation of such clusters impacted the multimodal imaging performance and pharmacokinetics of these tracers. We found that MPI signal intensity of the tracers in blood depends on their plasmatic clearance pharmacokinetics. Whole body mice MPI/MRI/NIRF, used to study the biodistribution of the injected NPs, showed primary distribution in liver and spleen. Biodistribution of tracers and their clearance pathway was further confirmed by MPI and NIRF signals from the excised organs where the Cy5.5 labeling enabled detailed anatomical mapping of the tracers.in tissue sections. These multimodal MPI tracers, combining the strengths of each imaging modality (e.g. resolution, tracer sensitivity and clinical use feasibility) pave the way for various in vitro and in vivo MPI applications.
authors.affiliation: Department of Materials Science, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Arami
authors.affiliation: LodeSpin Labs LLC, USA.
authors.forename: Amit P
authors.initials: AP
authors.lastname: Khandhar
authors.affiliation: Department of Materials Science, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Asahi
authors.initials: A
authors.lastname: Tomitaka
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Goodwill
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Conolly
authors.affiliation: Department of Materials Science, University of Washington, Seattle, WA, 98195, USA. Electronic address: kannanmk@uw.edu.
authors.forename: Kannan M
authors.initials: KM
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D003952:Diagnostic Imaging; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D057446:Hydrodynamics; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D064847:Multimodal Imaging; D036103:Nanotechnology; D055095:Optics and Photonics; D019047:Phantoms, Imaging; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature; D014018:Tissue Distribution
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011092:Polyethylene Glycols
keywords: Biodistribution and pharmacokinetics; Magnetic nanoparticles, Magnetic Resonance Imaging; Magnetic particle imaging; Multimodal contrast agents
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