title: Synthesis of 64Cu-labeled magnetic nanoparticles for multimodal imaging.
abstract: Complementary imaging modalities provide more information than either method alone can yield and we have developed a dual-mode imaging probe for combined magnetic resonance (MR) and positron emission tomography (PET) imaging. We have developed dual-mode PET/MRI active probes targeted to vascular inflammation and present synthesis of (1) an aliphatic amine polystyrene bead and (2) a novel superparamagnetic iron oxide nanoparticle targeted to macrophages that were both coupled to positron-emitting copper-64 isotopes. The amine groups of the polystyrene beads were directly conjugated with an amine-reactive form (isothiocyanate) of aza-macrocycle 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA). Iron oxide nanoparticles are dextran sulfate coated, and the surface was modified to contain aldehyde groups to conjugate to an amine-activated DOTA. Incorporation of chelated Cu-64 to nanoparticles under these conditions, which is routinely used to couple DOTA to macromolecules, was unexpectedly difficult and illustrates that traditional conjugation methods do not always work in a nanoparticle environment. Therefore, we developed new methods to couple Cu-64 to nanoparticles and demonstrate successful labeling to a range of nanoparticle types. We obtained labeling yields of 24% for the amine polystyrene beads and 21% radiolabeling yield for the anionic dextran sulfate iron oxide nanoparticles. The new coupling chemistry can be generalized for attaching chelated metals to other nanoparticle platforms.
authors.affiliation: Department of Biomedical Engineering, University of California-Davis, Davis, California 95616, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Jarrett
authors.forename: Björn
authors.initials: B
authors.lastname: Gustafsson
authors.forename: David L
authors.initials: DL
authors.lastname: Kukis
authors.forename: Angelique Y
authors.initials: AY
authors.lastname: Louie
mesh_terms: D000586:Amination; D002614:Chelating Agents / Q000737:chemistry; D003301:Copper Radioisotopes; D003432:Cross-Linking Reagents / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D049268:Positron-Emission Tomography; D013194:Staining and Labeling / Q000379:methods*
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D006573:Heterocyclic Compounds, 1-Ring; D011137:Polystyrenes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C000499:ferric oxide; D016264:Dextran Sulfate