Preclinical Proof of Concept Study towards Modifiable ²²⁵Ac-Chelators for Mild Condition Labeling and PSMA-targeting

Targeted alpha therapy is currently one of the most intensively investigated topics in radiopharmaceutical sciences and cancer management in nuclear medicine. Especially, the alpha emitter ²²⁵Ac provides excellent physical and chemical properties (t_1/2 = 10 d, 4 α and 2 β decays). Thus, it is consistently gaining an increasing interest for the radioligand therapy (RLT) of various tumor entities. The aim of this study was to synthesize macropa-based chelators that allow room temperature labeling and offer the modular functionalization properties for a straightforward coupling of temperature-sensitive biomolecules by e.g. click chemistry approaches. As a proof of concept study, the chelators were coupled to known PSMA-targeting vector molecules and then evaluated in vitro as well as in vivo.