title: Multimodality PET/MRI agents targeted to activated macrophages.
abstract: The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-(64)Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-(64)Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM(-1) s(-1), and an r 2 relaxivity of 83.9 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-(64)Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, CA, 95616, USA.
authors.forename: Chuqiao
authors.initials: C
authors.lastname: Tu
authors.forename: Thomas S C
authors.initials: TS
authors.lastname: Ng
authors.forename: Russell E
authors.initials: RE
authors.lastname: Jacobs
authors.forename: Angelique Y
authors.initials: AY
authors.lastname: Louie
mesh_terms: D000818:Animals; D002460:Cell Line; D003301:Copper Radioisotopes; D003911:Dextrans / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D013499:Surface Properties
chemical_list: D003301:Copper Radioisotopes; D003911:Dextrans; D005290:Ferric Compounds; C000499:ferric oxide