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 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/...

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Published in:Pharmaceutics 2022-11, Vol.14 (12), p.2566
Main Authors: Vermeulen, Koen, Van de Voorde, Michiel, Segers, Charlotte, Coolkens, Amelie, Rodriguez Pérez, Sunay, Daems, Noami, Duchemin, Charlotte, Crabbé, Melissa, Opsomer, Tomas, Saldarriaga Vargas, Clarita, Heinke, Reinhard, Lambert, Laura, Bernerd, Cyril, Burgoyne, Andrew R, Cocolios, Thomas Elias, Stora, Thierry, Ooms, Maarten
Format: Article
Language:English
Subjects:
Automation
Cell culture
Chromatography
DOTA-TATE
Energy
Laboratory animals
Neuroendocrine tumors
Neutrons
Nuclear reactors
Radiation therapy
samarium-153
SSTR2
targeted radionuclide therapy
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Summary: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 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am 153Sm. In this proof-of-concept study, we further evaluated the potential of high-Am 153Sm 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 153Sm 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 [153Sm]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 [153Sm]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 153Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14122566