Magnetic nanoparticles (MNPs) are becoming extremely diffused in biomedical field due to their unique physical properties and perspective use in theranostics. Although MNPs have been used as contrast media in MRI, obtaining multiprobe performance of these may also be useful to apply multimodality imaging. A particular feature of MNPs is that their disposition in vivo can be targeted in presence of an external magnetic field to achieve higher concentration and confinement in specific regions.We developed a simple strategy for labeling polymer-coated nanosystem based on magnetite (Fe3O4) nanoparticles and performed preliminary biodistribution studies to assess their use in targeted applications. Material and Methods: We used commercially-available aminodextran-coated iron oxide nanoparticles. N-hydoxylamine groups were produced by fuctionalisation of amino groups on the MNPs surface with BOC protected aminoxyacetic acid and conjugated with routinely produced 2-[18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) by a chemoselective reaction based on the formation of an oxime with the aldehyde of the acyclic sugar. Radiochemically pure FDG-labelled MNPs were recovered by ultrafiltration (Microcon®, Merck) and formulated in saline. The obtained nanoparticles were characterized by TEM and FTIR using non-radioactive FDG. PET/CT is being used in healthy CD-1 mice to assess biological distribution of the radiolabelled construct and study the influence of an external magnet on the nanosystem to drive MNPs biodistribution. In particular, [18F]FDG-MNPs were administered after a cylindrical magnet (N52, 1T) was placed on one tigh only. After MNPs administration, the mice were kept immobilized for 30 minutes and then sacrificed by inhalation of an anesthetic overdose. Afterwards, the magnet was removed and animals were scanned by microCT and the micro-PET for post-mortem whole-body imaging. Image were reconstructed and Volumes of Interest (VOIs) were drawn on both tighs. Results: A procedure for the radiolabelling of MNPs was achieved developing ad-hoc functionalised MNPs and [18F]FDG solution. The whole-body PET scan revealed higher radioactivity concentration in the bladder, kidneys and myocardium (@ 30' from injection). The ratio of measured activity in the two VoIs (magnet vs control) was M/C = 1.4-3.4 (min-max). The asymmetry of the radioactivity distribution can be ascribed to the presence of the magnetic field. Conclusion: A quick procedure for MNPs radiolabelling has been set up by simple oxime-forming reaction and the ability of external magnetic field to localise MNPs in a specific region was demonstrated. Further characterisation of the in vivo biodistribution is in progress as the study of specially designed magnets to achieve shaped MNPs concentration.
Functionalized Magnetic Nanoparticles for biomedical applications: radiolabelling and preliminary magnetically-driven biodistribution study
Panetta D;Gherardini L;Cinti C;Salvadori P
2013
Abstract
Magnetic nanoparticles (MNPs) are becoming extremely diffused in biomedical field due to their unique physical properties and perspective use in theranostics. Although MNPs have been used as contrast media in MRI, obtaining multiprobe performance of these may also be useful to apply multimodality imaging. A particular feature of MNPs is that their disposition in vivo can be targeted in presence of an external magnetic field to achieve higher concentration and confinement in specific regions.We developed a simple strategy for labeling polymer-coated nanosystem based on magnetite (Fe3O4) nanoparticles and performed preliminary biodistribution studies to assess their use in targeted applications. Material and Methods: We used commercially-available aminodextran-coated iron oxide nanoparticles. N-hydoxylamine groups were produced by fuctionalisation of amino groups on the MNPs surface with BOC protected aminoxyacetic acid and conjugated with routinely produced 2-[18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) by a chemoselective reaction based on the formation of an oxime with the aldehyde of the acyclic sugar. Radiochemically pure FDG-labelled MNPs were recovered by ultrafiltration (Microcon®, Merck) and formulated in saline. The obtained nanoparticles were characterized by TEM and FTIR using non-radioactive FDG. PET/CT is being used in healthy CD-1 mice to assess biological distribution of the radiolabelled construct and study the influence of an external magnet on the nanosystem to drive MNPs biodistribution. In particular, [18F]FDG-MNPs were administered after a cylindrical magnet (N52, 1T) was placed on one tigh only. After MNPs administration, the mice were kept immobilized for 30 minutes and then sacrificed by inhalation of an anesthetic overdose. Afterwards, the magnet was removed and animals were scanned by microCT and the micro-PET for post-mortem whole-body imaging. Image were reconstructed and Volumes of Interest (VOIs) were drawn on both tighs. Results: A procedure for the radiolabelling of MNPs was achieved developing ad-hoc functionalised MNPs and [18F]FDG solution. The whole-body PET scan revealed higher radioactivity concentration in the bladder, kidneys and myocardium (@ 30' from injection). The ratio of measured activity in the two VoIs (magnet vs control) was M/C = 1.4-3.4 (min-max). The asymmetry of the radioactivity distribution can be ascribed to the presence of the magnetic field. Conclusion: A quick procedure for MNPs radiolabelling has been set up by simple oxime-forming reaction and the ability of external magnetic field to localise MNPs in a specific region was demonstrated. Further characterisation of the in vivo biodistribution is in progress as the study of specially designed magnets to achieve shaped MNPs concentration.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
