Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [¹⁵³Sm]Sm-DOTA-TATE

Samarium-153 is a promising theranostic radionuclide, but low molar activities (A_m) 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-A_m ¹⁵³Sm. In this proof-of-concept study, we further evaluated the potential of high-A_m 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.