Smart contrast agents (CA) exhibit dynamic and reversible modulation of their relaxivity by specific physiological or biochemical triggers such as changes in pH, Ca2+ concentration or enzymatic activity (1-3). The extracellular concentration of Ca2+ plays important role in physiological and pathological processes in the nervous system. This led to the designing of a chelating system in which relaxivity is influenced as a function of Ca2+ concentration by changing coordination number around the paramagnetic metal ion. We synthesized a novel bifunctional bismacrocycle [Gd-(DO3A-DTPA-DO3A); Fig.] based on DO3A-EA [{4,7-Bis-carboxymethyl-10-(2-aminoethyl)-1,4,7,10-tetraaza-cyclododec-1-yl}-acetic acid] coupled to DTPA-bis-anhydride via a flexible alkyl spacer to form amide linkages. The overall yield of the four step synthesis starting from cyclen was 54%. This gadolinium-based agent has two limiting conformational states with different Ca2+ concentrations. It is hypothesized that in the absence of Ca2+, the carboxylates of the DTPA ligand interact with the Gd3+ ions which were held in DO3A, but in the presence of Ca2+, these carboxylates rearrange to chelate Ca2+ thereby allowing water to bind directly to Gd3+. Results: MR relaxivity of Gd-(DO3A-DTPA-DO3A) at pH 7.4 in the absence of Ca2+ was found to be r1 = (5.02±0.05) s-1mM-1. In the presence of 1mM Ca2+ r1 was (6.18±0.06) s-1mM-1 and 100mM Ca2+ r1 was (7.69±0.06) s-1mM-1. These data indicate 23% relaxivity enhancement from 0-1mM Ca2+ concentration under physiological conditions thus exhibiting a possibility for using it as extracellular calcium sensitive CA.