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

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, σth = 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.

Cutting edge rare earth radiometals: prospects for cancer theranostics

“…While focus on more conventional post-irradiation separation and purification of 153 Sm has been significant, investigation into new ways of increasing the specific activity has also gained traction. In a recent novel approach, a proof-of-concept method was demonstrated for the production of very high specific activity 153 Sm by using neutron bombardment in a high flux reactor in tandem with off-line mass separation (Voorde et al 2021 ). This method involved irradiating highly enriched [ 152 Sm]Sm(NO 3 ) 3 targets converted from [ 152 Sm]Sm 2 O 3 (98.7%) with neutron beam energies of 2.0–2.5 × 10 14 n/cm 2 /s, and subsequent mass separation with laser resonance enhanced ionisation to dramatically increase the specific activity of the product radionuclide (Voorde et al 2021 ).…”

“…In a recent novel approach, a proof-of-concept method was demonstrated for the production of very high specific activity 153 Sm by using neutron bombardment in a high flux reactor in tandem with off-line mass separation (Voorde et al 2021 ). This method involved irradiating highly enriched [ 152 Sm]Sm(NO 3 ) 3 targets converted from [ 152 Sm]Sm 2 O 3 (98.7%) with neutron beam energies of 2.0–2.5 × 10 14 n/cm 2 /s, and subsequent mass separation with laser resonance enhanced ionisation to dramatically increase the specific activity of the product radionuclide (Voorde et al 2021 ). Mass separation efficiencies achieved were 4.5% on average with a maximum of 12.7%, and the 153 Sm underwent radiochemical processing and post-purification using DGA extraction chromatography, ion exchange chromatography with α-HIBA and extraction chromatography with LN3 extraction resin to give the final [ 153 Sm]SmCl 3 formulation that was deemed suitable for radiolabelling.…”

“…Near-quantitative yields were achieved for the radiolabelling of S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid ( p -SCN-Bn-DOTA, see Fig. 8 ) and the method demonstrated the potential for TBq activites of clinical-grade 153 Sm to be produced for radiolabelling purposes (Voorde et al 2021 ). This approach is quite new, and while results are promising, further optimisation of the mass separation protocol to increase the separation efficiency and greater availability of high flux neutron reactors are required before widespread application of this method is feasible.…”

Effect of Gd3+, La3+, Lu3+ Co-Doping on the Morphology and Luminescent Properties of NaYF4:Sm3+ Phosphors

“…Samarium compounds are of interest in medicine and the production of functional nanoparticles. For example, the decay energy of the samarium 153 Sm nuclide allows using this isotope for cancer therapy and SPECT imaging [ 32 , 33 ]. Sm 3+ ions are also known to be used as a part of optically active materials because of their orange luminescence, originating from the 4 G 5/2 → 6 H J/2 (J = 5, 7, and 9) transitions [ 14 , 34 , 35 , 36 , 37 ].…”

Evaluation of Therapeutic Efficacy and Imaging Capabilities of 153Sm2O3-Loaded Polystyrene Microspheres for Intra-Tumoural Radionuclide Therapy of Liver Cancer Using Sprague-Dawley Rat Model

“…The microspheres are non-radioactive during synthesis until they are sent for neutron activation before the treatment. A large quantity of high specific activity samarium-153 ( 153 Sm) can be produced via direct neutron capture process, 152 Sm(n,γ) 153 Sm due to its high thermal neutron activation cross-section (206 barns) [ 16 ]. 153 Sm has an optimal half-life of 46.3 h, low γ-ray energy (E γ = 103 keV) for imaging and high β − radiation (E β − (max) = 808 keV) for therapy [ 17 ].…”