Relaxometric Investigations and MRI Evaluation of a Liposome-Loaded pH-Responsive Gadolinium(III) Complex

Accurate measurement of the tissue pH in vivo by MRI may be of clinical value for both diagnosis and selection/monitoring of therapy. To act as pH reporters, MRI contrast agents have to provide responsiveness to pH that does not require prior knowledge of the actual concentration of the contrast agent. This work deals with the use of a paramagnetic gadolinium(III) complex, loaded into liposomes, whose relaxometric properties are affected by the pH of the medium. In this system, the amphiphilic metal complex, which contains a moiety whose protonation changes the coordination properties of the metal chelate, experiences a different intraliposomial distribution depending on the pH conditions. The pH of the solution can be unambiguously identified by exploiting the peculiar characteristics of the resulting NMRD profiles, and a ratiometric pH-responsive method has been set up by comparing the relaxation enhancement at different magnetic field strengths.