Polymeric conjugates of Gd(3+)-diethylenetriaminepentaacetic acid and dextran. 1. Synthesis, characterization, and...

Macromolecular conjugates of dextran and diethylenetriaminepentaacetic acid (DTPA), aimed to complex gadolinium, were synthesized to obtain contrast agents for nuclear magnetic resonance imaging with good paramagnetic properties and long intravascular persistence. These conjugates were prepared from dextran 40 (Mn = 38 kg/mol and Mw = 43 kg/mol), which was first carboxymethylated. Then amines were introduced by reacting ethylenediamine with dextran carboxylic acid groups in the presence of 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline. DTPA was then covalently linked to aminated dextran by using three different coupling procedures (DTPA bisanhydride, dicyclohexylcarbodiimide/N-hydroxysuccinimide, and isobutyl chloroformate). The different final products were compared in terms of DTPA contents, molecular masses, and sizes, and it was proved that the last synthesis step led to a small fraction of cross-linked chains as Mn was between 128 and 166 kg/mol and Mw between 332 and 371 kg/mol. In spite of this partial cross-linking which theoretically decreases the complexation capacity of the dextran-linked DTPA molecules, the Gd(3+)-complexed conjugates exhibited relaxivities at 20 MHz/mol of gadolinium-2.5 times as great as that of free GdDTPA2-.