Synthesis and Characterization of Iron Oxide MNP Tracers

Three iron oxide MNP tracer samples, UW-1, UW-2, and LS-1 were used in phantom experiments reported here. Physical properties of the samples are listed in Table 1. Tracers were synthesized according to protocols described in previous work [31 (link)]. Synthesis protocols were based on thermolysis of iron (III) oleate with excess oleic acid in 1-octadecene. After synthesis, oleic acid coated MNPs were transferred from organic to aqueous phase using a PEG-ylated amphiphilic polymer [poly(maleic anhydride-alt-1 octadecene)-poly(ethylene glycol); PEG M_w ~ 5,000 Da (UW-1, UW-2) or 20,000 Da (LS-1)]. All three samples showed comparable magnetic behavior measured by MPS and vibrating sample magnetometer (VSM); the thicker polymer coating of sample LS-1 was designed to prolong blood circulation time for ongoing animal studies unrelated to this work. MNP magnetic size was determined by bright field TEM imaging (FEI, Hillsboro, OR) and by fitting a Langevin function to room-temperature magnetization curves (VSM, Lakeshore, Westerville, OH) to determine the median magnetic core diameter (d₀) and geometric standard deviation (exp(σ)), assuming the particle sizes satisfied a log normal distribution of the form $$g\left(d_C\right)=\frac{1}{\sigma d_C\sqrt{2\pi }}\exp -\frac{{\left[\ln (\frac{d_C}{d_0}\right]}^2}{2{\sigma }^2},$$ where d_c is the magnetic core diameter [19 (link)]. The number-weighted diameter distribution was determined to enable direct comparison with TEM. For fitting M(H) data, the saturation magnetization, M_s, was determined from measured iron concentration; average M_s was 2.8×10⁵ A/m, (UW-1: 1.5×10⁵; UW-2: 3.7×10⁵; LS-1: 3.3×10⁵ A/m), similar to the measured M_s of Resovist^® (3.0×10⁵). Sample iron concentration was measured by inductively coupled plasma - optical emission spectrophotometer (ICP) (Perkin Elmer, Waltham, MA). Z-average hydrodynamic diameter, d_H, of aqueous-phase MNPs was determined by Dynamic Light Scattering (DLS) (Zetasizer, Malvern Instruments, Malvern, UK).