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...

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Autores principales: 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
Lenguaje:eng
Publicado: 2022
Materias:
Acceso en línea:https://dx.doi.org/10.3390/pharmaceutics14122566
http://cds.cern.ch/record/2849042
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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.
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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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