Lanthanide(III) chelates of DTPA bis(amide) glycoconjugates:: Potential imaging agents targeted at the asyaloglycoprotein receptor

The synthesis and characterisation of a new class of DTPA bis(amide) linked glycoconjugates of different sugars [lactose (Lac) and galactose (Gal)] and valencies (di and tetra) and their Ln(III) complexes is reported. The H-1 NMR spectra of the Sm-III and Eu-III complexes of DTPAGal(2), DTPAGal(4), and DTPALac(2), obtained between 7 and 80 degrees C, indicate that several of the four possible diastereoisomeric pairs of structures resulting from the chirality of the three bound DTPA nitrogen atoms are present in solution, with different relative populations. The dynamic effects of racemisation of the central nitrogen atom in the NMR spectra show that this process is fast at 60 degrees C for the Sm-III complexes and slow at 7 degrees C for the Eu-III complexes. The in vitro r(1) nuclear magnetic relaxation dispersion (NMRD) of the water protons of the Gd-III-DTPA bis(amide) glycoconjugate containing two lactosyl moieties [Gd-III-DTPALaC(2)] was studied, yielding the molecular parameters that govern its relaxivity. Its r(1) value, at 25 degrees C and 20 MHz, is 13% higher than that reported for Gd-III chelates of lower molecular weight DTPA bis(amides), such as DTPA-BMA, consistent with a five times larger tau(R) value. The water exchange rate, k(ex), and the electron spin relaxation parameters of the Gd-III-DTPALaC(2) complex are within the usual range for similar Gd-III-DTPA bis(amide) chelates. (c) Wiley-VCH Verlag GmbH & Co.