Bis(phenylethylamide) Derivatives of Gd‐DTPA as Potential Receptor‐Specific MRI Contrast Agents

Abstract

Abstract DTPA‐bis(amide) derivatives bearing phenyl, phenol or catechol groups that mimic side chains of naturally occurring amino acids, such as phenylalanine, tyrosine or dopamine, were synthesized and characterized by elemental analysis, electrospray mass spectrometry, NMR spectroscopy and IR spectroscopy. The gadolinium(III) complexes of the ligands DTPA‐bis(tyramide) [DTPA‐(TA) 2 ], DTPA‐bis(3‐hydroxytyramide) [DTPA‐(HTA) 2 ] and DTPA‐bis(phenylalanine ethyl ester) [DTPA‐(PAE) 2 ], were prepared and then studied in vitro by 17 O NMR spectroscopy and by nuclear magnetic relaxation dispersion (NMRD) measurements. The residence time of the coordinated water in gadolinium(III) complexes was obtained from 17 O NMR relaxometric T 2 measurements. At 310 K, the following τ M values were obtained: Gd‐DTPA‐(TA) 2 582 ns, Gd‐DTPA‐(HTA) 2 372 ns and Gd‐DTPA‐(PAE) 2 809 ns. As shown by the analysis of the proton NMRD profiles, the larger proton relaxivities of the gadolinium(III) complexes at 310 K relative to that of the parent Gd‐DTPA complex are mainly because of the increase in the rotationalcorrelation time. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)