C-11 radiolabeling of iron-oxide nanoparticles for dual-modality PET/MR imaging Ramesh Sharma †‡* , Youwen Xu † , Sung Won Kim † , Michael J. Schueller † , David Alexoff † , S. David Smith † , Wei Wang || , and David Schlyer †* † Brookhaven National Laboratory, Upton, NY 11973 ‡ Gordon Battelle Memorial Institute, Columbus, OH 43201 || Oak Ridge National Laboratory, Oak Ridge, TN 37831 * Corresponding authors: ramesharma26@gmail.com, schlyer@bnl.gov Supporting Information (1) Synthesis, surface functionalization and purification of magnetic iron-oxide nanoparticles Deionized H 2 O (resistance ~18 MΩ·cm) was used throughout the experiments, and all reactions were performed under N 2 atmosphere or in closed containers to protect samples from oxidation. Superparamagnetic Fe 3 O 4 nanoparticles (SPIO NPs) were prepared by a chemical co- precipitation method 1 at room temperature (23 ºC). Typically, 0.2 M FeCl 3 (anhydrate, EM Science) and 0.1 M FeSO 4 ·7H 2 O (J. T. Baker) were mixed in 100 mL H 2 O under N 2 . Then 10 mL of 29.5 wt% NH 3 ·H 2 O (J. T. Baker) was injected into the mixture with vigorous stirring. Upon adding the NH 3 ·H 2 O, the color of the mixture turned from brown to black immediately, implying formation of iron hydroxide. After stirring overnight for dehydration, the deep brown Fe 3 O 4 NPs were collected by magnet and washed three times with deionized water. The Fe 3 O 4 NPs were surface-modified with –COOH or –NH 2 groups through covalent bonding. To functionalize the surface with –COOH groups, the Fe 3 O 4 nanoparticles were dispersed in a 250 mL mixture of ethanol and H 2 O (volume ratio 20: 1) at pH~8.5 adjusted by NH 3 ·H 2 O, and then 2 mL of N(trimethoxysilylpropyl) ethylenediamine-triacetic acid-trisodium salt (35% in water, Gelest) as a silane coupling agent was added drop by drop while stirring. After 12 hours, the reaction mixture was adjusted to pH ~3.5 by HCl, and the reaction was terminated after 12 hours. The -COOH functionalized Fe 3 O 4 NPs were collected by a bar magnet and repeatedly washed with deionized water five times. In the washing process, particles were re-dispersed by a vortex mixer and separated by a magnet so that ionic and nonmagnetic impurities could be removed. To functionalize the surface of Fe 3 O 4 NPs with –NH 2 groups, the same protocol was repeated using a different silane agent, 3-aminopropyltriethoxysilane (APTES), (99+%, Gelest), which contains a –NH 2 functional group. Surface charge properties were evaluated by zeta potential measurements with the dynamic light scattering method (Brookhaven ZetaPlus analyzer). The measurements show zeta Electronic Supplementary Material (ESI) for Nanoscale This journal is © The Royal Society of Chemistry 2013