Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE
Samarium-153 is a promising theranostic radionuclide, but low molar activities (A<sub>m</sub>) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of <sup>152</sup>Sm in the SCK...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2566 |
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| author | Koen Vermeulen Michiel Van de Voorde Charlotte Segers Amelie Coolkens Sunay Rodriguez Pérez Noami Daems Charlotte Duchemin Melissa Crabbé Tomas Opsomer Clarita Saldarriaga Vargas Reinhard Heinke Laura Lambert Cyril Bernerd Andrew R. Burgoyne Thomas Elias Cocolios Thierry Stora Maarten Ooms |
| author_facet | Koen Vermeulen Michiel Van de Voorde Charlotte Segers Amelie Coolkens Sunay Rodriguez Pérez Noami Daems Charlotte Duchemin Melissa Crabbé Tomas Opsomer Clarita Saldarriaga Vargas Reinhard Heinke Laura Lambert Cyril Bernerd Andrew R. Burgoyne Thomas Elias Cocolios Thierry Stora Maarten Ooms |
| author_sort | Koen Vermeulen |
| collection | DOAJ |
| description | Samarium-153 is a promising theranostic radionuclide, but low molar activities (A<sub>m</sub>) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of <sup>152</sup>Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-A<sub>m</sub> <sup>153</sup>Sm. In this proof-of-concept study, we further evaluated the potential of high-A<sub>m</sub> <sup>153</sup>Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR<sub>2</sub>) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with <sup>153</sup>Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR<sub>2</sub>-expressing CA20948 cells. In vitro biological evaluation showed that [<sup>153</sup>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 [<sup>153</sup>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 <sup>153</sup>Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production. |
| first_indexed | 2024-03-09T15:58:41Z |
| format | Article |
| id | doaj.art-bf8a094d04184b509d6e9a3d216dfaea |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:58:41Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-bf8a094d04184b509d6e9a3d216dfaea2023-11-24T17:18:09ZengMDPI AGPharmaceutics1999-49232022-11-011412256610.3390/pharmaceutics14122566Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATEKoen Vermeulen0Michiel Van de Voorde1Charlotte Segers2Amelie Coolkens3Sunay Rodriguez Pérez4Noami Daems5Charlotte Duchemin6Melissa Crabbé7Tomas Opsomer8Clarita Saldarriaga Vargas9Reinhard Heinke10Laura Lambert11Cyril Bernerd12Andrew R. Burgoyne13Thomas Elias Cocolios14Thierry Stora15Maarten Ooms16NURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumInstitute for Nuclear and Radiation Physics, KU Leuven, 3000 Leuven, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumResearch in Dosimetric Applications, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumInstitute for Nuclear and Radiation Physics, KU Leuven, 3000 Leuven, BelgiumMEDICIS, Conseil Européen pour la Recherche Nucléaire (CERN), 1211 Geneva, SwitzerlandInstitute for Nuclear and Radiation Physics, KU Leuven, 3000 Leuven, BelgiumNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumInstitute for Nuclear and Radiation Physics, KU Leuven, 3000 Leuven, BelgiumMEDICIS, Conseil Européen pour la Recherche Nucléaire (CERN), 1211 Geneva, SwitzerlandNURA Research Group, Belgian Nuclear Research Center (SCK CEN), 2400 Mol, BelgiumSamarium-153 is a promising theranostic radionuclide, but low molar activities (A<sub>m</sub>) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of <sup>152</sup>Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-A<sub>m</sub> <sup>153</sup>Sm. In this proof-of-concept study, we further evaluated the potential of high-A<sub>m</sub> <sup>153</sup>Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR<sub>2</sub>) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with <sup>153</sup>Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR<sub>2</sub>-expressing CA20948 cells. In vitro biological evaluation showed that [<sup>153</sup>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 [<sup>153</sup>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 <sup>153</sup>Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.https://www.mdpi.com/1999-4923/14/12/2566targeted radionuclide therapysamarium-153DOTA-TATESSTR<sub>2</sub> |
| spellingShingle | Koen Vermeulen Michiel Van de Voorde Charlotte Segers Amelie Coolkens Sunay Rodriguez Pérez Noami Daems Charlotte Duchemin Melissa Crabbé Tomas Opsomer Clarita Saldarriaga Vargas Reinhard Heinke Laura Lambert Cyril Bernerd Andrew R. Burgoyne Thomas Elias Cocolios Thierry Stora Maarten Ooms Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE Pharmaceutics targeted radionuclide therapy samarium-153 DOTA-TATE SSTR<sub>2</sub> |
| title | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE |
| title_full | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE |
| title_fullStr | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE |
| title_full_unstemmed | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE |
| title_short | Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [<sup>153</sup>Sm]Sm-DOTA-TATE |
| title_sort | exploring the potential of high molar activity samarium 153 for targeted radionuclide therapy with sup 153 sup sm sm dota tate |
| topic | targeted radionuclide therapy samarium-153 DOTA-TATE SSTR<sub>2</sub> |
| url | https://www.mdpi.com/1999-4923/14/12/2566 |
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