Preparation and water relaxation properties of proteins labeled with paramagnetic metal chelates.

The proteins bovine serum albumin (BSA) and bovine immunoglobulin (IgG) have been labeled with paramagnetic gadolinium (III) and manganese (II) complexes using the bifunctional chelate approach. Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were attached to several free amino groups on the proteins using cyclic anhydride forms of these ligands. The incorporation of the metal ions Gd+3 and Mn+2 into the chelating groups yielded highly paramagnetic proteins. The water relaxation ability (or relaxivity) of the protein-bound chelates at 20 MHz was found to be superior to that of the free metal complexes. Differences in relaxivity between the DTPA and EDTA conjugates could largely be accounted for by differences in the metal ion exposure to water. This labeling technique can be used in the preparation of intravascular NMR contrast agents (like paramagnetically-labeled human serum albumin) or target-specific agents (labeled monoclonal antibodies or fibrinogen).