Cross-Linked DTPA Polysaccharides for Magnetic Resonance Imaging

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Abstract
An attempt was made to develop a macromolecular paramagnetic contrast agent that would be easily and inexpensively synthesized, low in toxicity, and quickly eliminated from the body after completion of the desired imaging studies. Under more rigorous conditions than attainable with proteins, the bis-anhydride of DTPA was reacted in anhydrous, hot DMSO with dextrans ranging in size from 17,000 molecular weight (MW) to 150,000 MW in various ratios of DTPA to glucose units from 1:1 to 1:40. Up to several hundred DTPA units per saccharide complex could be attached with this technique. Depending on the initial polysaccharide length and ratio of DTPA to glucose units, various degrees of cross-linking occur. Average MW of the polymers ranging from 17,000 to particles several million MW could be synthesized. The ester bond thus formed is stable for prolonged periods in solution. Depending on the polymer size, soluble material, gels, or particles are formed. Relaxation rates of the soluble material are similar or better than Gd-DTPA on a molar basis of Gd3+. The particulate material demonstrates T2 shortening out of proportion to T1, as expected for solid material, from increased susceptibility effects.