Production of Mass-Separated Erbium-169 Towards the First Preclinical in vitro Investigations

Zeynep Talip; Francesca Borgna; Cristina Müller; Jiri Ulrich; Charlotte Duchemin; Joao P Ramos; Thierry Stora; Ulli Köster; Youcef Nedjadi; Vadim Gadelshin; Valentin N Fedosseev; Frederic Juget; Claude Bailat; Adelheid Fankhauser; Shane G Wilkins; Laura Lambert; Bruce Marsh; Dmitry Fedorov; Eric Chevallay; Pascal Fernier; Roger Schibli; Nicholas P van der Meulen

doi:10.3389/fmed.2021.643175

Production of Mass-Separated Erbium-169 Towards the First Preclinical in vitro Investigations

Front Med (Lausanne). 2021 Apr 22:8:643175. doi: 10.3389/fmed.2021.643175. eCollection 2021.

Authors

Zeynep Talip¹, Francesca Borgna¹, Cristina Müller^{1

2}, Jiri Ulrich³, Charlotte Duchemin^{4

5}, Joao P Ramos^{4

5}, Thierry Stora⁴, Ulli Köster⁶, Youcef Nedjadi⁷, Vadim Gadelshin^{4

8

9}, Valentin N Fedosseev⁴, Frederic Juget⁷, Claude Bailat⁷, Adelheid Fankhauser¹⁰, Shane G Wilkins⁴, Laura Lambert⁴, Bruce Marsh⁴, Dmitry Fedorov¹¹, Eric Chevallay⁴, Pascal Fernier⁴, Roger Schibli^{1

2}, Nicholas P van der Meulen^{1

3}

Affiliations

¹ Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen, Switzerland.
² Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
³ Laboratory of Radiochemistry, Paul Scherrer Institute, Villigen, Switzerland.
⁴ European Organization for Nuclear Research (CERN), Geneva, Switzerland.
⁵ Institute for Nuclear and Radiation Physics, Catholic University of Leuven, Leuven, Belgium.
⁶ Institut Laue-Langevin, Grenoble, France.
⁷ Institute of Radiation Physics, University Hospital and University of Lausanne, Lausanne, Switzerland.
⁸ Institute of Physics, Johannes Gutenberg University, Mainz, Germany.
⁹ Institute of Physics and Technology, Ural Federal University, Yekaterinburg, Russia.
¹⁰ Analytic Radioactive Materials, Paul Scherrer Institute, Villigen, Switzerland.
¹¹ Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute, Gatchina, Russia.

Abstract

The β^--particle-emitting erbium-169 is a potential radionuclide toward therapy of metastasized cancer diseases. It can be produced in nuclear research reactors, irradiating isotopically-enriched ¹⁶⁸Er₂O₃. This path, however, is not suitable for receptor-targeted radionuclide therapy, where high specific molar activities are required. In this study, an electromagnetic isotope separation technique was applied after neutron irradiation to boost the specific activity by separating ¹⁶⁹Er from ¹⁶⁸Er targets. The separation efficiency increased up to 0.5% using resonant laser ionization. A subsequent chemical purification process was developed as well as activity standardization of the radionuclidically pure ¹⁶⁹Er. The quality of the ¹⁶⁹Er product permitted radiolabeling and pre-clinical studies. A preliminary in vitro experiment was accomplished, using a ¹⁶⁹Er-PSMA-617, to show the potential of ¹⁶⁹Er to reduce tumor cell viability.

Keywords: Er-169; activity standardization; electromagnetic isotope separation; in vitro studies; lanthanide-separation; laser resonance ionization.

Copyright © 2021 Talip, Borgna, Müller, Ulrich, Duchemin, Ramos, Stora, Köster, Nedjadi, Gadelshin, Fedosseev, Juget, Bailat, Fankhauser, Wilkins, Lambert, Marsh, Fedorov, Chevallay, Fernier, Schibli and van der Meulen.