Physicochemical Characterization of P760, a New Macromolecular Contrast Agent with High Relaxivity

Abstract

Abstract P760‐Gd, a hydrophilic derivative of DOTA‐Gd with a molecular mass of 5.6 kDa, has been characterized in various media: aqueous solution, protein‐containing solution, and Zn 2+ ‐containing solution. Several investigations have been carried out, including the determination of the number of inner‐sphere water molecules by laser‐induced luminescence of the europium complex, water 1 H nuclear magnetic relaxation rates as a function of field strength, and 17 O relaxometry of water of the gadolinium complex, pulsed magnetic field gradient spin echo of proton, and 2 H transverse relaxation rates of the labeled lanthanum analogue. The large proton relaxivity of P760‐Gd in water results from the long rotational correlation time of the hydrated complex (τ R ≈︁ 2 ns at 310 K). As with DOTA‐Gd, no significant Zn 2+ transmetallation process was observed by proton relaxometry. Finally, analysis of the non‐covalent binding of P760‐Gd to serum proteins by proton relaxometry showed that P760‐Gd does not interact with human serum albumin. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)