The aim of this study was to develop a dual-modality PET/MR imaging probe by radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized with water soluble stabilizer 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), with the positron emitter Gallium-68. Magnetite nanoparticles (Fe₃O₄ MNPs) were synthesized via coprecipitation method and were stabilized with DPD. The Fe₃O₄-DPD MNPs were characterized based on their structure, morphology, size, surface charge, and magnetic properties. In vitro cytotoxicity studies showed reduced toxicity in normal cells, compared to cancer cells. Fe₃O₄-DPD MNPs were successfully labeled with Gallium-68 at high radiochemical purity (>91%) and their stability in human serum and in PBS was demonstrated, along with their further characterization on size and magnetic properties. The ex vivo biodistribution studies in normal Swiss mice showed high uptake in the liver followed by spleen. The acquired PET images were in accordance with the ex vivo biodistribution results. Our findings indicate that Ga68-Fe₃O₄-DPD MNPs could serve as an important diagnostic tool for biomedical imaging.

Radiolabeled albumin microspheres with encapsulated citric acid-coated magnetite nanoparticles were developed as a targeting approach to localize both radioactivity and magnetic energy at the tumor site. We present in vitro and in vivo studies of yttrium-90 (⁹⁰Y)-labeled human serum albumin magnetic microspheres (HSAMMS) as a multifunctional agent for possible applications in a bimodal radionuclide-hyperthermia cancer therapy. The HSAMMS were produced using a modified emulsification-heat stabilization technique and contained 11 nm magnetite nanoparticles coated with citric acid, distributed as inhomogeneous clusters within the albumin microspheres. The size, size distribution and the morphology of magnetite nanoparticles and HSAMMS were determined by FESEM, HRTEM and SEM/FIB dual beam. The average particle size of the complete HSAMMS was 20 μm, and they exhibited superparamagnetic behavior at room temperature. The in vitro experiments (in saline and human serum) revealed the high stability of the labeled HSAMMS in saline and human serum after 72 h. Following the intravenous administration of the ⁹⁰Y-HSAMMS in rats, 88.81% of the activity localizes in the lungs after 1 h, with 82.67% remaining after 72 h. These data on ⁹⁰Y-HSAMMS provide good evidence for their potential use in bimodal radionuclide-hyperthermia cancer therapy.

As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (¹⁷⁷Lu), generating ¹⁷⁷Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by ¹⁷⁷Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of ¹⁷⁷Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the ¹⁷⁷Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, ¹⁷⁷Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy.

Radiolabeled magnetic nanoparticles (MNPs) coated with hydrophilic phosphate ligands, i.e., imidodiphosphate (IDP) and inositol hexaphosphate (IHP), were developed as multifunctional agents to localize both radioactivity and magnetic energy at a tumor site. The coating of MNPs with phosphates made them biocompatible, increased their colloidal stability and allowed binding of the radionuclide ⁹⁰Y to the available functional groups on the surface of the MNPs. IDP and IHP have not hitherto been used for the coating of MNPs and the results of this study of the functionalized MNPs showed that the phosphate groups influenced the modification of the surface of MNPs. Characterization of the MNPs was performed using X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering and laser Doppler electrophoresis. The specific power absorption values obtained for MNPs (46.95–80.76 W g⁻¹) in different physiological media indicated their possible application in hyperthermia treatment. Both types of coated MNPs were ⁹⁰Y-labeled in a reproducible high yield (>98%). In vitro studies of ⁹⁰Y-MNPs in saline and human serum showed their high stability after 72 h. The biodistribution pattern of the MNPs after intravenous administration to healthy Wistar rats was followed by the radiotracer method, revealing that ⁹⁰Y-Fe₃O₄-IDP and ⁹⁰Y-Fe₃O₄-IHP MNPs were predominantly found in the liver (85.21% ID and 86.22% ID), followed by the spleen (9.23% ID and 8.82% ID) and the lungs (1.53% ID and 1.53% ID). The results of this comprehensive study showed that radiolabeled biocompatible phosphate magnetic complexes hold great promise for therapeutic uses combining magnetic hyperthermia and radiotherapy.