title: Stable Radiolabeling of Sulfur-Functionalized Silica Nanoparticles with Copper-64.
abstract: Nanoparticles labeled with radiometals enable whole-body nuclear imaging and therapy. Though chelating agents are commonly used to radiolabel biomolecules, nanoparticles offer the advantage of attaching a radiometal directly to the nanoparticle itself without the need of such agents. We previously demonstrated that direct radiolabeling of silica nanoparticles with hard, oxophilic ions, such as the positron emitters zirconium-89 and gallium-68, is remarkably efficient. However, softer radiometals, such as the widely employed copper-64, do not stably bind to the silica matrix and quickly dissociate under physiological conditions. Here, we overcome this limitation through the use of silica nanoparticles functionalized with a soft electron-donating thiol group to allow stable attachment of copper-64. This approach significantly improves the stability of copper-64 labeled thiol-functionalized silica nanoparticles relative to native silica nanoparticles, thereby enabling in vivo PET imaging, and may be translated to other softer radiometals with affinity for sulfur. The presented approach expands the application of silica nanoparticles as a platform for facile radiolabeling with both hard and soft radiometal ions.
authors.affiliation: Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Department of Chemistry, Hunter College of the City University of New York , New York, New York 10065, United States.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York , New York, New York 10016, United States.
authors.forename: Travis M
authors.initials: TM
authors.lastname: Shaffer
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Stefan
authors.initials: S
authors.lastname: Harmsen
authors.affiliation: Department of Chemistry, Hunter College of the City University of New York , New York, New York 10065, United States.
authors.forename: Emaad
authors.initials: E
authors.lastname: Khwaja
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Department of Radiology, Weill Cornell Medical College , New York, New York 10065, United States.|Center for Molecular Imaging & Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Kircher
authors.affiliation: Department of Chemistry, Hunter College of the City University of New York , New York, New York 10065, United States.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York , New York, New York 10016, United States.
authors.forename: Charles Michael
authors.initials: CM
authors.lastname: Drain
authors.affiliation: Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Department of Radiology, Weill Cornell Medical College , New York, New York 10065, United States.|Center for Molecular Imaging & Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.|Department of Pharmacology, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Jan
authors.initials: J
authors.lastname: Grimm
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes / Q000737:chemistry*; D008297:Male; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D049268:Positron-Emission Tomography; D012822:Silicon Dioxide; D013455:Sulfur / Q000737:chemistry*
chemical_list: D003301:Copper Radioisotopes; D013455:Sulfur; D012822:Silicon Dioxide
keywords: PET imaging; radiolabeling; silica nanoparticles; surface functionalization