Production of Sm-153 With Very High Specific Activity for Targeted Radionuclide Therapy

Michiel Van de Voorde; Charlotte Duchemin; Reinhard Heinke; Laura Lambert; Eric Chevallay; Thomas Schneider; Miranda Van Stenis; Thomas Elias Cocolios; Thomas Cardinaels; Bernard Ponsard; Maarten Ooms; Thierry Stora; Andrew R Burgoyne

doi:10.3389/fmed.2021.675221

Production of Sm-153 With Very High Specific Activity for Targeted Radionuclide Therapy

Front Med (Lausanne). 2021 Jul 19:8:675221. doi: 10.3389/fmed.2021.675221. eCollection 2021.

Authors

Affiliations

¹ Belgian Nuclear Research Center, Institute for Nuclear Materials Science, Mol, Belgium.
² Department of Physics and Astronomy, Institute for Nuclear and Radiation Physics, KU Leuven, Leuven, Belgium.
³ European Organization for Nuclear Research, MEDICIS, Geneva, Switzerland.
⁴ European Organization for Nuclear Research, Thin Film Lab, Geneva, Switzerland.
⁵ Department of Chemistry, KU Leuven, Leuven, Belgium.

Abstract

Samarium-153 (¹⁵³Sm) is a highly interesting radionuclide within the field of targeted radionuclide therapy because of its favorable decay characteristics. ¹⁵³Sm has a half-life of 1.93 d and decays into a stable daughter nuclide (¹⁵³Eu) whereupon β^- particles [E = 705 keV (30%), 635 keV (50%)] are emitted which are suitable for therapy. ¹⁵³Sm also emits γ photons [103 keV (28%)] allowing for SPECT imaging, which is of value in theranostics. However, the full potential of ¹⁵³Sm in nuclear medicine is currently not being exploited because of the radionuclide's limited specific activity due to its carrier added production route. In this work a new production method was developed to produce ¹⁵³Sm with higher specific activity, allowing for its potential use in targeted radionuclide therapy. ¹⁵³Sm was efficiently produced via neutron irradiation of a highly enriched ¹⁵²Sm target (98.7% enriched, σ_th = 206 b) in the BR2 reactor at SCK CEN. Irradiated target materials were shipped to CERN-MEDICIS, where ¹⁵³Sm was isolated from the ¹⁵²Sm target via mass separation (MS) in combination with laser resonance enhanced ionization to drastically increase the specific activity. The specific activity obtained was 1.87 TBq/mg (≈ 265 times higher after the end of irradiation in BR2 + cooling). An overall mass separation efficiency of 4.5% was reached on average for all mass separations. Further radiochemical purification steps were developed at SCK CEN to recover the ¹⁵³Sm from the MS target to yield a solution ready for radiolabeling. Each step of the radiochemical process was fully analyzed and characterized for further optimization resulting in a high efficiency (overall recovery: 84%). The obtained high specific activity (HSA) ¹⁵³Sm was then used in radiolabeling experiments with different concentrations of 4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA). Even at low concentrations of p-SCN-Bn-DOTA, radiolabeling of 0.5 MBq of HSA ¹⁵³Sm was found to be efficient. In this proof-of-concept study, we demonstrated the potential to combine neutron irradiation with mass separation to supply high specific activity ¹⁵³Sm. Using this process, ¹⁵³SmCl₃ suitable for radiolabeling, was produced with a very high specific activity allowing application of ¹⁵³Sm in targeted radionuclide therapy. Further studies to incorporate ¹⁵³Sm in radiopharmaceuticals for targeted radionuclide therapy are ongoing.

Keywords: cancer; mass separated radionuclides; nuclear medicine; radiolanthanides; resonant laser ionization; samarium-153; targeted radionuclide therapy; theranostics.