Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd3? complex linked to an aminobis(methylenephosphonate) group for chelating Ca2? was synthesized and investigated. The longitudinal relaxivity (r1) of this complex decreases during the relaxometric titration with Ca2? from 5.76 to 3.57mM-1 s-1 upon saturation. The r1 is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu3? complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).