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 (t1/2 = 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.