Design of Functional Chiral Cyclen-Based Radiometal Chelators for Theranostics

A series of water-soluble chiral cyclen-based chelators with chemical handles for selective targeting have been synthesized (cyclen = 1,4,7,10-Tetraazacyclododecane). Optical studies, relaxivity measurements, and competitive titrations were performed to show the versatility of these chiral chelators. The complexations of L3, L4, and L5 with Lu³⁺, Y³⁺, Sc^3+, and Cu²⁺ were successfully demonstrated in around 90% to 100% yields. Efficient and rapid radiolabeling of L5 with ¹⁷⁷Lu was achieved under mild conditions with 96% yield. The chelators exhibit near quantitative labeling efficiencies with a wide range of radiometal ions, which are promising for the development of targeting specific radiopharmaceutical and molecular magnetic resonance imaging contrast agents.