POLYMERIC CONJUGATES OF GD3-DIETHYLENETRIAMINEPENTAACETIC ACID AND DEXTRAN .1. SYNTHESIS, CHARACTERIZATION, AND PARAMAGNETIC PROPERTIES()

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 param agnetic properties and long intravascular persistence. These conjugate s were prepared from dextran 40 (<(M)over bar (n)> = 38 kg/mol and <(M )over bar (w)> 43 kg/mol), which was first carboxymethylated. Then ami nes were introduced by reacting ethylenediamine with dextran carboxyli c acid groups in the presence of 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihyd roquinoline. DTPA was then covalently linked to aminated dextran by us ing three different coupling procedures (DTPA bisanhydride, dicyclohex ylcarbodiimide/N-hydroxysuccinimide, and isobutyl chloroformate). The different final products were compared in terms of DTPA contents, mole cular masses, and sizes, and it was proved that the last synthesis ste p led to a small fraction of cross-linked chains as <(M)over bar (n)> was between 128 and 166 kg/mol and <(M)over bar (w)> between 332 and 3 71 kg/mol. In spite of this partial cross-linking which theoretically decreases the complexation capacity of the dextran-linked DTPA molecul es, the Gd3+-complexed conjugates exhibited relaxivities at 20 MHz/mol of gadolinium-2.5 times as great as that of free GdDTPA(2-).