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 (A m ) 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-A m   153 Sm. In this proof-of-concept study, we further evaluated the potential of high-A m   153 Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR 2 ) 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 SSTR 2 -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.