MR contrast agents whose efficiency depends on the concentration of signaling molecules may be used to directly visualize neuronal activation. The so-called ‘smart’ contrast agents for magnetic resonance imaging exhibit dynamic and reversible modulation of their relaxivity by specific physiological or biochemical triggers such as changes in pH, Ca2+ concentration or enzymatic activity1. The extracellular concentration of Ca2+ plays an important role in the physiological and pathological processes of the nervous system; it led us to design chelating systems in which the relaxivity is influenced by the Ca2+ concentration. We synthesized three novel bifunctional bismacrocycles [Figure] based on Ln-DO3A-EA coupled to EDTA/DTPA-bis-anhydride via amide bonds. Results: The relaxivity changes upon increasing Ca2+ concentration of our three novel Gd(III) complexes largely depends on the structure of the ligands. In contrast to no significant relaxivity change of Gd2L3 upon Ca2+ addition, Gd2L1 an