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

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Article number	675221
Journal	Frontiers in Medicine
Volume	8
DOIs	https://doi.org/10.3389/fmed.2021.675221
State	Published - Jul 19 2021
Externally published	Yes

Funding

This work was performed as part of the NURA research program of SCK CEN. This work was supported by Research Foundation Flanders FWO (Belgium) via the FWO IRI CERN ISOLDE I002619N and FWO SBO Tb-IRMA-V S005019N funding awarded to KU Leuven. The authors would like to thank the CERN HSE-RP team and Frank Vanderlinden (SCK CEN) for establishing a smooth coordination of the nuclear transports between CERN and SCK CEN, as well as reception of the radioactive targets. MV, MO, and AB would like to thank Guiseppe Modolo and Dimitri Schneider (Forschungszentrum J?lich GmbH) for their help with the hot ICP-MS analyses in this work. The Radiochemical Analyses group at SCK CEN is acknowledged for their help with gamma spectrometry and ICP-OES analyses. Funding. This work was performed as part of the NURA research program of SCK CEN. This work was supported by Research Foundation Flanders FWO (Belgium) via the FWO IRI CERN ISOLDE I002619N and FWO SBO Tb-IRMA-V S005019N funding awarded to KU Leuven.

Funders	Funder number
CERN
Fonds Wetenschappelijk Onderzoek

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fmed.2021.675221

Cite this

@article{4a605bca9a404e7c9ffdb7f9167b6d94,

title = "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.",

keywords = "cancer, mass separated radionuclides, nuclear medicine, radiolanthanides, resonant laser ionization, samarium-153, targeted radionuclide therapy, theranostics",

author = "{Van de Voorde}, Michiel and Charlotte Duchemin and Reinhard Heinke and Laura Lambert and Eric Chevallay and Thomas Schneider and {Van Stenis}, Miranda and Cocolios, {Thomas Elias} and Thomas Cardinaels and Bernard Ponsard and Maarten Ooms and Thierry Stora and Burgoyne, {Andrew R.}",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Van de Voorde, Duchemin, Heinke, Lambert, Chevallay, Schneider, Van Stenis, Cocolios, Cardinaels, Ponsard, Ooms, Stora and Burgoyne.",

year = "2021",

month = jul,

day = "19",

doi = "10.3389/fmed.2021.675221",

language = "English",

volume = "8",

journal = "Frontiers in Medicine",

issn = "2296-858X",

publisher = "Frontiers Media",

}

TY - JOUR

T1 - Production of Sm-153 With Very High Specific Activity for Targeted Radionuclide Therapy

AU - Van de Voorde, Michiel

AU - Duchemin, Charlotte

AU - Heinke, Reinhard

AU - Lambert, Laura

AU - Chevallay, Eric

AU - Schneider, Thomas

AU - Van Stenis, Miranda

AU - Cocolios, Thomas Elias

AU - Cardinaels, Thomas

AU - Ponsard, Bernard

AU - Ooms, Maarten

AU - Stora, Thierry

AU - Burgoyne, Andrew R.

PY - 2021/7/19

Y1 - 2021/7/19

N2 - 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.

AB - 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.

KW - cancer

KW - mass separated radionuclides

KW - nuclear medicine

KW - radiolanthanides

KW - resonant laser ionization

KW - samarium-153

KW - targeted radionuclide therapy

KW - theranostics

UR - http://www.scopus.com/inward/record.url?scp=85111588531&partnerID=8YFLogxK

U2 - 10.3389/fmed.2021.675221

DO - 10.3389/fmed.2021.675221

M3 - Article

AN - SCOPUS:85111588531

SN - 2296-858X

VL - 8

JO - Frontiers in Medicine

JF - Frontiers in Medicine

M1 - 675221

ER -

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

Abstract

Funding

Keywords

UN SDGs

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