Izvestia Vysshikh Uchebnykh Zawedeniy. Yadernaya Energetika

The peer-reviewed scientific and technology journal. ISSN: 0204-3327

Development of radiopharmaceutical based on magnetic nanoparticles for targeted alpha-therapy

11/15/2018 2018 - #04 nuclear medicine and biology

Mokhodoeva O.B. Shkinev V.M. Dzhenloda R.Kh. Zakhodyaeva Yu.A. Voshkin A.A.

DOI: https://doi.org/10.26583/npe.2018.4.11

UDC: 615.28

The method of targeted radionuclide therapy using short-lived alpha emitters with a number of unique nuclear-physical and biochemical properties allows to achieve a high local cytotoxic effect with minimal impact on healthy tissues. The first alpha-radiopharmaceutical “Xofigo” represents radium dichloride-223, administered intravenously in the form of a solution, and has been used since 2013 in palliative therapy of bone metastases. The purpose of the present study was to investigate magnetic nanoparticles and their sorption ability towards radium-223 to develop nanoconstructs for targeted alpha-radiotherapy of oncological diseases.

Magnetic nanoparticles based on magnetite were synthesized and characterized. The following two methods were used for synthesizing nanoparticles: the traditional method of co-precipitation and the new method based on a two-phase extraction system, when the formation of nanoparticles occurs on the interface layer. In the present study we select the system with polyethylene glycol (PEG) 3000.

The method of direct radiolabeling of magnetite nanoparticles by sorption of radium-223, prepared using a 227Ac/227Th radioisotope generator, was developed. Optimal conditions were selected for ensuring the quantitative extraction of radium-223 from the solution by Fe3O4 nanoparticles. Magnetite nanoparticles coated with silica and PEG-3000 shells were developed for enhancing the aggregation stability and biocompatibility. It was found that the prepared nanoconstructs based on magnetite and radium-223 are sufficiently stable in physiological media and promising for application in targeted alpha-radiotherapy.


  1. Asadi N., Davaran S., Panahi Y., Hasanzadeh A., Malakootikhah J., Fallah Moafi H., Akbarzadeh A. Application of nanostructured drug delivery systems in immunotherapy of cancer: a review. Artificial Cells Nanomedicine and Biotechnology. 2017, no. 45, pp. 18-23.
  2. Kunz-Schughart L.A., Dubrovska A., Peitzsch C., Ewe A., Aigner A., Schellenburg S., Muders M.H., Hampel S., Cirillo G., Iemma F., Tietze R., Alexiou C., Stephan H., Zarschler K., Vittorio O., Kavallaris M., Parak W.J., Madler L., Pokhrel S. Nanoparticles for radiooncology: Mission, vision, challenges. Biomaterials. 2017, no. 120, pp. 155-184.
  3. Seidl C. Radioimmunotherapy with α-particle-emitting radionuclides. Immunotherapy. 2014, v. 6, pp. 431-458.
  4. Aghevlian S., Boyle A.J., Reilly R.M. Radioimmunotherapy of cancer with high linear energy transfer (LET) radiation delivered by radionuclides emitting alpha-particles or Auger electrons. Advanced Drug Delivery Reviews. 2017, v. 109, pp. 102-118.
  5. Sobolev A.C. Modular Nanotransporters: A Multitarget Platform for Anticancer Drug Delivery. Vestnik Rossijskoy Akademii Nauk. 2013, v. 83, pp. 324-335.
  6. Sobolev A.S., Aliev R.A., Kalmykov S.N. Radionuclides emitting short-range particles and modular nanotransporters for their delivery to target cancer cells. Russian Chemical Reviews. 2016, v. 85, pp. 1011-1032.
  7. Kluetz P.G., Pierce W., Maher V.E., Zhang H., Tang S.H., Song P.F., Liu Q., Haber M.T., Leutzinger E.E., Al-Hakim A., Chen W., Palmby T., Alebachew E., Sridhara R., Ibrahim A., Justice R., Pazdur R. Radium Ra 223 Dichloride Injection: US Food and Drug Administration Drug Approval Summary. Clinical Cancer Research. 2014, v. 20, no. 1, pp. 9-14.
  8. Guseva L.I. Radioisotope Generators of Short-Lived α-Emitting Radionuclides Promising for Use in Nuclear Medicine. Radiochemistry. 2014, v. 56, no. 5, pp. 451-467.
  9. Mokhodoeva O., Guseva L., Dogadkin N. Isolation of generator-produced Ra-223 in 0.9% NaCl solutions containing EDTA for direct radiotherapeutic studies. J. Radioanal. Nucl. Chem. 2015, v. 304, pp. 449-453.
  10. Radovic M., Vranjes-Duric S., Nikolic N., Jankovic D., Goya G.F., Torres T.E., Calatayud M.P., Bruvera I.J., Ibarra M.R., Spasojevic V., Jancar B., Antic B. Development and evaluation of Y-90-labeled albumin microspheres loaded with magnetite nanoparticles for possible applications in cancer therapy. Journal of Materials Chemistry. 2012, v. 22, no. 45, pp. 24017-24025.
  11. Mehta R.V. Synthesis of magnetic nanoparticles and their dispersions with special reference to applications in biomedicine and biotechnology. Materials Science & Engineering CMaterials for Biological Applications. 2017, no. 79, pp. 901-915.
  12. Mokhodoeva O., Vlk M., Malkova E., Kukleva E., Micholovav P., Sh tamberg K., Sh louf M., Dzhenloda R., Kozempel J. Study of 223Ra uptake mechanism by Fe3O4 nanoparticles: towards new prospective theranostic SPIONs. Journal of Nanoparticle Research. 2016, v. 18, no.10, pp. 301-312.
  13. Voshkin A.A., Shkinev V.M., Zakhodyaeva Y.A. A new extraction method for the preparation of zinc oxide nanoparticles in aqueous two-phase systems. Russian Journal of Physical Chemistry A. 2017, v. 91, no. 2, pp. 226-228.
  14. Voshkin A.A., Shkinev V.M., Zakhodyaeva Y.A. Extraction method for the preparation of metal oxides nano-sized crystals. Patent RF, no. 2625877, 2017.
  15. Shkinev V.M., Zakhodyaeva Yu.A., Dzhenloda R.Kh., Mokhodoeva O.B., Voshkin A.A. Synthesis of magnetic iron oxide nanoparticles at the interface of the polyethylene glycol-ammonium sulfate-water extraction system. Mendeleev Communications. 2017, no. 27, pp. 485-486.
  16. Santra S., Tapec R., Theodoropoulou N., Dobson J, Hebard A., Weihong T. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: the effect of nonionic surfactants. Langmuir. 2001, v. 17, pp. 2900-2906.

radium-223, magnetic nanoparticles magnetite delivery nanoconstructs radiopharmaceuticals targeted alpha-therapy short-lived alpha radionuclides