Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE
Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of $^{152}$Sm in the SCK CEN BR2 reactor with mass separation at...
Autores principales: | , , , , , , , , , , , , , , , , |
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Lenguaje: | eng |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://dx.doi.org/10.3390/pharmaceutics14122566 http://cds.cern.ch/record/2849042 |
_version_ | 1780976870558269440 |
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author | Vermeulen, Koen Van de Voorde, Michiel Segers, Charlotte Coolkens, Amelie Pérez, Sunay Rodriguez Daems, Noami Duchemin, Charlotte Crabbé, Melissa Opsomer, Tomas Vargas, Clarita Saldarriaga Heinke, Reinhard Lambert, Laura Bernerd, Cyril Burgoyne, Andrew R Cocolios, Thomas Elias Stora, Thierry Ooms, Maarten |
author_facet | Vermeulen, Koen Van de Voorde, Michiel Segers, Charlotte Coolkens, Amelie Pérez, Sunay Rodriguez Daems, Noami Duchemin, Charlotte Crabbé, Melissa Opsomer, Tomas Vargas, Clarita Saldarriaga Heinke, Reinhard Lambert, Laura Bernerd, Cyril Burgoyne, Andrew R Cocolios, Thomas Elias Stora, Thierry Ooms, Maarten |
author_sort | Vermeulen, Koen |
collection | CERN |
description | Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of $^{152}$Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am $^{153}$Sm. In this proof-of-concept study, we further evaluated the potential of high-Am $^{153}$Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with $^{153}$Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [$^{153}$Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [$^{153}$Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated $^{153}$Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production. |
id | cern-2849042 |
institution | Organización Europea para la Investigación Nuclear |
language | eng |
publishDate | 2022 |
record_format | invenio |
spelling | cern-28490422023-02-23T10:57:44Zdoi:10.3390/pharmaceutics14122566http://cds.cern.ch/record/2849042engVermeulen, KoenVan de Voorde, MichielSegers, CharlotteCoolkens, AmeliePérez, Sunay RodriguezDaems, NoamiDuchemin, CharlotteCrabbé, MelissaOpsomer, TomasVargas, Clarita SaldarriagaHeinke, ReinhardLambert, LauraBernerd, CyrilBurgoyne, Andrew RCocolios, Thomas EliasStora, ThierryOoms, MaartenExploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATEHealth Physics and Radiation EffectsSamarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of $^{152}$Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am $^{153}$Sm. In this proof-of-concept study, we further evaluated the potential of high-Am $^{153}$Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with $^{153}$Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [$^{153}$Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [$^{153}$Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated $^{153}$Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.oai:cds.cern.ch:28490422022 |
spellingShingle | Health Physics and Radiation Effects Vermeulen, Koen Van de Voorde, Michiel Segers, Charlotte Coolkens, Amelie Pérez, Sunay Rodriguez Daems, Noami Duchemin, Charlotte Crabbé, Melissa Opsomer, Tomas Vargas, Clarita Saldarriaga Heinke, Reinhard Lambert, Laura Bernerd, Cyril Burgoyne, Andrew R Cocolios, Thomas Elias Stora, Thierry Ooms, Maarten Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE |
title | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE |
title_full | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE |
title_fullStr | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE |
title_full_unstemmed | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE |
title_short | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [$^{153}$Sm]Sm-DOTA-TATE |
title_sort | exploring the potential of high-molar-activity samarium-153 for targeted radionuclide therapy with [$^{153}$sm]sm-dota-tate |
topic | Health Physics and Radiation Effects |
url | https://dx.doi.org/10.3390/pharmaceutics14122566 http://cds.cern.ch/record/2849042 |
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