Gd3+-loaded polyion complex for pH depiction with magnetic resonance imaging

Abstract

In clinical diagnosis, gadolinium (Gd) ion/low molecular weight chelater complexes have been used as MRI contrast agents that disperse throughout a particular tissue and cause a brighter appearance in MRI. In order to provide a novel imaging concept for MRI, a contrast agent in which the T1-relaxation shortening activity (R1 relaxivity) changes in response to the pH differences was studied. We prepared a polyion complex (PIC) consisting of a polyanionic Gd-chelater, poly(diethylenetriamine-N,N,N',N',N'-pentaaceto, DTPA) (1,3-propanediamide) (denoted as 1a) loaded with Gd ions at a [Gd]/[DTPA unit] ratio of 0.2 (denoted as 1b), and a polycation, poly[2- (diethylamino)ethyl methacrylate] (denoted as 2). The stoichiometric (based on ionic groups) mixture of lb and 2 formed complex coacervates from pH 5 to pH 8. The R1 relaxivity of Gd3+ in the complex was considerably influenced by the pH, and the relative signal intensity changed from 4 at pH 7.2 to 11 at pH 5.0, as determined by an MRI phantom study. The pH responsivity of the complex solution varied with the composition of the PIC (i.e., the mixing ratio of 1b and 2), allowing us to modulate the pH sensibility. The ionic charge balance and swelling of PIC seemingly were related to the pH-dependent R1 relaxivity change. It is expected that the PIC-based MRI contrast agent may provide a novel category of MRI methods and be useful in improving the detectability of an MRI-based diagnosis.