Gd-aminoethyl-DO3A complexes: A novel class of pH-sensitive MRI contrast agents

Molecular imaging relies on the availability of imaging probes designed to modify their efficiency in the presence of a specific parameter, among which pH is one of the most investigated. Introduction of an aminoethyl moiety into the well-known DO3A platform imparts the desired pH sensitivity to the corresponding Gd³⁺ complex. The amine group is accessible and easy to functionalize; in particular, the possibility of tuning its pK_AH through N-substitution makes it a good pH-responsive functionality to access a novel class of tailored pH-sensitive MRI contrast agents. This was demonstrated by a relaxometric study on a functionalized Gd-DO3A complex bearing a simple primary amine group and comparison with the results of the corresponding N,N-dimethyl analogue. Gd³⁺ complexes of aminoethyl-substituted DO3A show pH-sensitive behaviour with a relaxivity jump close to physiologically relevant pH values. The response to pH of this novel platform may be fine tuned by N-substitution.