title: Gd(3+)-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 T(1)-relaxation shortening activity (R(1) 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 1b and 2 formed complex coacervates from pH 5 to pH 8. The R(1) relaxivity of Gd(3+) 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 R(1) 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.
authors.affiliation: Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mikawa
authors.forename: N
authors.initials: N
authors.lastname: Miwa
authors.forename: M
authors.initials: M
authors.lastname: Bräutigam
authors.forename: T
authors.initials: T
authors.lastname: Akaike
authors.forename: A
authors.initials: A
authors.lastname: Maruyama
mesh_terms: D002412:Cations; D003287:Contrast Media; D019786:Gadolinium DTPA; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods*; D019047:Phantoms, Imaging
chemical_list: D002412:Cations; D003287:Contrast Media; D019786:Gadolinium DTPA