title: Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore-expanded mesoporous silica nanoparticles for PET.
abstract: Functional nanoparticles are highly interesting imaging agents for positron emission tomography (PET) due to the possibility of multiple incorporation of positron emitting radionuclides thus increasing the signal strength. Furthermore, long-term nanoparticle biodistribution tests with increased signal-to-noise ratio can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous silica nanoparticles, MSNs, have recently attracted a lot of interest as both imaging agents and carriers for drugs in vitro and in vivo. Here we present results related to the synthesis of PET imageable MSNs carrying the long-lived (89)Zr isotope (half-life of 78.4 hours). Here, (89)Zr(4+) was immobilized through covalent attachment of the complexing agent p-isothiocyanatobenzyldesferrioxamine (DFO-NCS) to large-pore MSNs. Due to the presence of the high DFO content on the MSNs, quantitative (89)Zr(4+) labeling was achieved within just a few minutes, and no subsequent purification step was needed in order to remove non-complexed (89)Zr(4+). The stability of the (89)Zr-labeled MSNs against leaching of (89)Zr(4+) was verified for 24 hours. The high signal strength of the (89)Zr-DFO-MSNs was evidenced by successful PET imaging using a mouse model at particle loadings one order of magnitude lower than those previously applied in PET-MSN studies. The biodistribution followed the same trends as previously observed for MSNs of different sizes and surface functionalities. Taken together, our results suggest that (89)Zr-DFO-MSNs are promising PET imaging agents for long-term in vivo imaging.
authors.affiliation: Department of Inorganic Chemistry II, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany. mlinden@uni-ulm.de.
authors.forename: Larissa
authors.initials: L
authors.lastname: Miller
authors.forename: Gordon
authors.initials: G
authors.lastname: Winter
authors.forename: Benjamin
authors.initials: B
authors.lastname: Baur
authors.forename: Barbara
authors.initials: B
authors.lastname: Witulla
authors.forename: Christoph
authors.initials: C
authors.lastname: Solbach
authors.forename: Sven
authors.initials: S
authors.lastname: Reske
authors.forename: Mika
authors.initials: M
authors.lastname: Lindén
mesh_terms: D000818:Animals; D007553:Isotope Labeling; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D012822:Silicon Dioxide / Q000737:chemistry*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous; D015040:Zirconium / Q000737:chemistry
chemical_list: D019275:Radiopharmaceuticals; D012822:Silicon Dioxide; D015040:Zirconium