Preparation of Fe-52 core labeled iron oxide nanoparticle contrast agent and evaluation of its dual PET/MRI imaging potential in mouse

1535 Objectives The focus of this work was to prepare contrast agent based on superparamagnetic iron oxide nanoparticle platform with PET isotope Fe-52 incorporated into the inorganic core of the nanoparticles and explore its potential for simultaneous PET/MRI imaging. Methods The positron emitter Fe-52 (T1/2=8.275 h, mean Eβ+=340 keV; 55.5%) was prepared by proton irradiation of natural nickel (natNi ) foil at the Brookhaven Linac Isotope Producer at 109 MeV to induce the natNi(p,3pxn)52Fe reaction. Radioisotope Fe-52 was selectively separated from Ni and co-produced radioimpurities using anion-exchange column. Iron oxide nanoparticles were prepared by a co-precipitation technique in aqueous media and stabilized with citrate. Radiolabeling with Fe-52 was carried out at room temperature by adsorption of stable Fe3+ along with Fe-52 onto nanoparticles. Optimal conditions for the labeling procedure as well as the biodistribution of the nanoparticles in mice were determined using Fe-59 radiotracer. Fe-52 labeled nanoparticles (0.1 mg) were injected into the mouse tail vein. Simultaneous dynamic PET and MRI imaging were carried out on the 9.4T micro MRI fitted with a PET insert for a period of 3 hours. The images were coregistered and ROI drawn on the images to produce time activity curves for both PET and MRI. Results Nanoparticles with specific activity 0.46 μCi (Fe-52)/µg, with an average hydrodynamic diameter of 100 nm were obtained with the labeling yield of 80%. Dual PET/MRI image showed rapid liver localization of iron nanoparticles, as expected for this agent with no washout over the period of the experiment. Conclusions The nanoparticle fabrication approach resulted in high labeling yield and in vivo stability. Nanoparticles retained their magnetic properties and were suitable for dual PET/MRI image acquisition. Research Support Brookhaven Science Associates, LLC under Contract No. DE-AC02-98CH1-886 with the U.S. Department of Energy