High-resolution NMR imaging of paramagnetic liposomes targeted to a functionalized surface.

ABSTRACT

A major application of molecular MR imaging is receptor mapping of cells lining blood vessels with targeted contrast agents. Since these agents accumulate at interfaces, knowledge of their influence on the relaxation process in this specific configuration is a prerequisite for understanding their working principle. A methodology is presented to study the influence of targeted contrast agents on surface relaxation in vitro. Paramagnetic liposomes attached to a functionalized surface were studied with high-resolution NMR imaging. The surface was prepared by covering a solid substrate with a layer of collagen. Paramagnetic liposomes were targeted to this surface by functionalizing the liposomes with collagen adhesion protein CNA-35. With a saturation-recovery sequence, 1D magnetization profiles with a resolution of 5 microm were measured in water in contact with the surface. Analytical predictions, obtained with the Bloch-Torrey equation, perfectly agreed with the experimental data. Therefore, the magnitude of the surface relaxation rate could be determined from the measurements without any assumption. By using the relaxivity of liposome solutions the surface coverage by liposomes could be estimated. With the presented methodology the behavior of Gd-based targeted contrast agents at biological interfaces can be studied in vitro. Their influence on relaxation processes can be characterized and quantified.