Title: Barium ferrite magnetic nanoparticles labeled with 223Ra: a new potential magnetic radiobioconjugate for targeted alpha therapy
Publication Year: 2019
JRC N°: JRC114229
ISSN: 0362-4803 (online)
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC114229
DOI: 10.1002/jlcr.3724
Type: Articles in periodicals and books
Abstract: 223Ra, as radium chloride, is the first commercially and widely used α-radiopharmaceutical. It is easily obtained from the 227Ac/223Ra generator. However, 223Ra is used only for treatment of bone metastases derived from primary prostate and breast cancers. Unfortunately, the lack of an appropriate bifunctional ligand for radium was the reason why 223Ra has not yet found application in receptor targeted therapy. Because Ra2+ and Ba2+ are nearly identical cations in our studies we propose to use barium ferrite (BaFe12O19) nanoparticles as multifunctional carriers for 223Ra radionuclide for targeted α therapy. Barium hexaferrite nanoparticles labelled with 223Ra were synthesized by a modified autoclave method described by Drofenik et al [1]. The reaction mixture of FeCl3, BaCl2 and 223RaCl2 was alkalized with NaOH solution. Next, the reaction mixture was stirred in autoclave at 210oC for 6 h. Obtained radioactive, magnetic [223Ra]BaFe12O19 nanoparticles were washed with distilled water and hydrochloric acid (0.001 M HCl). Obtained magnetic BaFe12O19 nanoparticles were characterized by transmission emission microscopy and dynamic light scattering. The diameter of synthesized nanoparticles was ~20 nm and the determined magnetization of nanoparticles in room temperature was about 42 emu/g. Yield of labelling was about 70% (for 100 kBq 223Ra). Stability of the obtained radioactive nanoparticles was tested in various biological solutions: 0.01M PBS, 0.9% NaCl and in human blood serum. It is confirmed that 223Ra was highly retained inside nanoparticles in every tested solution. Only about 20% of 211Pb (recoiled decay product of 223Ra) was found in solution. In order to synthesize a radiobioconjugate having affinity to HER2 receptors, the monoclonal antibody trastuzumab was conjugated to the obtained barium ferrite nanoparticles. Firstly, the surface of barium ferrite nanoparticles was modified with 3-phosphonopropionic acid linker using a method described by Mohapatra et al [2], and then, the monoclonal antibodies were coupled to the barium ferrite nanoparticles using the carbodiimide chemistry. Synthesized bioconjugate was characterized by thermogravimetric analysis, dynamic light scattering and were tested for stability in biological fluids. The obtained [223Ra]BaFe12O19-CEPA-trastuzumab radiobioconjugate almost quantitatively retains 223Ra and majority of the daughter products. In-vitro biological studies indicate that [223Ra]BaFe12O19-CEPA-trastuzumab exhibits high affinity and cytotoxicity to the to the SKOV3 ovarian cell line.
JRC Directorate:Nuclear Safety and Security

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