99mTc-, 90Y-, and 177Lu-Labeled Iron Oxide Nanoflowers Designed for Potential Use in Dual Magnetic Hyperthermia/Radionuclide Cancer Therapy and Diagnosis

Development of a complex based on iron oxide nanoparticles (IONPs) for diagnosis and dual magnetic hyperthermia/radionuclide cancer therapy accomplishing high yields of radiolabeling and great magnetic heat induction is still a challenge. We report here the synthesis of citric acid, poly(acrylic acid) (PAA) and poly(ethylene glycol) coated IONPs and their labeling with three radionuclides, namely, technetium (Tc-99m), yttrium (Y-90), and lutetium (Lu-177), aiming at potential use in cancer diagnosis and therapy. Polyolsynthesized IONPs are a flowerlike structure with 13.5 nm spherically shaped cores and 24.8 nm diameter. PAA-coated nanoparticles (PAA@IONP) showed the best characteristics such as easy radiolabeling with very high yields (>97.5%) with all three radionuclides, and excellent in vitro stabilities with less than 10% of radionuclides detaching after 24 h. Heating ability of PAA@IONP in an alternating external magnetic field showed intrinsic loss power value of 7.3 nH m(2)/kg, which is one of higher reported values. Additionally, PAA@IONP itself presented no significant cytotoxicity to the CT-26 cancer cells, reaching IC50 at 60 mu g/mL. However, under the external magnetic field, they show hyperthermia-mediated cells killing, which correlated with the magnetic field strength and time of exposure. Since PAA@IONP are easy to prepare, biocompatible, and with excellent magnetic heat induction, these nanoparticles radiolabeled with high-energy beta emitters Y-90 and Lu-177 have valuable potential as agent for dual magnetic hyperthermia/radionuclide therapy, while radiolabeled with Tc-99m could be used in diagnostic imaging.