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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.

Erbium 169Er is one of the most interesting radiolanthanides for new potential receptor-targeted β− therapy applications due to its low energy β− emissions, very low intensity ɣ rays and the possibility to use 68Ga or 44Sc as companion for diagnostic in a theranostics approach. Currently it can be produced in reactors through the neutron activation of highly enriched 168Er. The low specific activity of the produced carrier-added 169Er is limiting its use for receptor-targeted therapy. Nonetheless it is used for radiosynoviorthesis of small joints. The aim of this work is to develop a new large-scale production method for the supply of very high specific activity 169Er. Highly enriched 168Er target has been irradiated at ILL nuclear reactor and shipped to CERN-MEDICIS. There, the irradiated sample has been mass separated in order to isolate 169Er from the high amount of remaining stable 168Er. The proof of principle for a preclinical dose production has been demonstrated with a collection of ≈17 MBq. The specific activity obtained was ≈240 GBq/mg (≈200 times higher than the product obtained at End of Bombardment – EOB) and the overall separation efficiency was ≈0.2%. Several improvements for the future have been identified and are promising. One of them is the installation of the new laser laboratory at CERN-MEDICIS that will allow to improve the selective ionization of erbium atoms leading to an increase of the efficiency of the method. This method can provide the supply of high specific activity 168Er, first for preclinical studies, and opens also the potential for future large-scale supply. [ABSTRACT FROM AUTHOR]

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 168 Er 2 O 3 . 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 169 Er from 168 Er 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 169 Er. The quality of the 169 Er product permitted radiolabeling and pre-clinical studies. A preliminary in vitro experiment was accomplished, using a 169 Er-PSMA-617, to show the potential of 169 Er to reduce tumor cell viability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (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.)