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Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Polymeric contrast agents for magnetic resonance imaging: synthesis and characterization of gadolinium diethylenetriaminepentaacetic acid conjugated to polysaccharides.
Bioconjugate Chemistry 1990 November
The synthesis and characterization of polysaccharides esterified with gadolinium diethylenetriaminepentaacetic acid (GdDTPA) are described. The results of several synthetic methods are presented for esterification of dextrans and inulin with DTPA. One method results in highly conjugated products labeled with an average of 0.4 mol of GdDTPA/mol of glucopyranose unit in dextrans of up to 70,800 average molecular weight and 0.5 mol of GdDTPA/mol of fructofuranose unit in inulin. Chromatographic and potentiometric evidence supporting the absence of significant chelate cross-linking of the conjugated polysaccharides is presented. The thermodynamic stability constant, log K (Gd3+ + L4(-)----GdL-), of the complexes was 18.0 +/- 0.2 based on an independent chelate model. In vitro ester hydrolysis of the GdDTPA-dextran 70,800 (at 37 degrees C, pH = 7.4 phosphate buffer) occurs with a half-life of 21 h. The agents exhibit T1 relaxivities ranging from 1.5 to 2.3 times that of GdDTPA at 100 MHz, and decreasing in vitro relaxivity with increasing molecular weight of the dextran carrier was observed. Phantom MRI studies indicate that the T1 and T2 effects of the complexes differ from those of GdDTPA, with the polysaccharide-bound complexes exhibiting a considerably faster drop in relative signal intensity with increased concentration in T1 and T2 weighted pulse sequences.
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