(450f) Production and Application of PET Nuclide 52Fe At Brookhaven Linac Isotope Producer for Radiolabeling of Iron Oxide Nanoparticles to Obtain PET/MRI Probe

The radioisotope ⁵²Fe is a positron emitter with nuclear properties suitable for imaging applications. Emission of a positron (mean E_β+=340 keV;55.5%) and two gamma-rays 168.7 keV (99.2%), 377.7 keV (1.68%) allows both positron emission tomography (PET) and single photon computer tomography (SPECT) imaging. Production of this isotope can be accomplished in a proton accelerator using ⁵⁵Mn(p,4n)or  ^natNi(p, xn) nuclear reactions at proton energies above 50 MeV. The use of this isotope has been limited in part due to its short half-life (8.275 h) which makes centralized production and distribution impractical.

Being an isotope of iron, radioisotope ⁵²Fe is ideal for the core labeling of ultrasmall super paramagnetic iron oxide nanoparticles (USPIO). USPIO is a molecular resonance imaging (MRI) contrast agent which appears dark on the MRI image. When labeled with the PET isotope, such as ⁵²Fe, both PET and MRI images can be acquired.  In a core labeling approach the radionuclide becomes an integral part of the inorganic center of the NP and, therefore the attachment through the ligands is not needed.

About 40 mCi of Fe-52 decay corrected the end of bombardment (EOB) was produced using ⁵⁸Ni(p,3p4n)⁵²Fe reaction by  proton irradiation of natural nickel foils at 109 MeV at Brookhaven Linac Isotope Producer. Iron-52 was chemically separated from nickel and cobalt isotopes by anion-exchange chromatography. USPIO were prepared by co-precepitation of Fe²⁺/Fe³⁺=1/2 salts with NH₄OH and stabilized by citrate. Radiolabeling with ⁵²Fe was carried out at pH=6 in sodium acetate buffer for 30 min at room temperature. The labeling yield of 78% was achieved. The obtained nanoparticles were used to obtain MRI and PET images.