DENDRIMER-BASED METAL-CHELATES - A NEW CLASS OF MAGNETIC-RESONANCE-IMAGING CONTRAST AGENTS

We have developed a new class of magnetic resonance imaging contrast a gents with large proton relaxation enhancements and high molecular rel axivities. The reagents are built from the polyamidoamine form of Star burst(TM) dendrimers in which free amines have been conjugated to the chelator natobenzyl)-6-methyl-diethylenetriaminepentaacetic acid. The dendrimer gadolinium poly-chelates have enhancement factors, i.e., the ratio of the relaxivity per Gd(III) ion to that of Gd(III)-diethylene triaminepentaacetic acid, of up to 6. These factors are more than twic e those observed for analogous metal-chelate conjugates formed with se rum albumins, polylysine, or dextran. One of the dendrimer-metal chela te conjugates has 170 gadolinium ions bound, which greatly exceeds the number bound to other macromolecular agents reported in the literatur e, and has a molecular relaxivity of 5,800 (mM . s)(-1), at 25 MHz, 20 degrees C, and pH of 7.4. We observed that these dendrimer-based agen ts enhance conventional MR images and 3D time of flight MR angiograms, and that those with molecular weights of 8,508 and 139,000 g/mole hav e enhancement half lives of 40 +/- 10 and 200 +/- 100 min, much longer than the 24 +/- 4 min measured for Gd(III)diethylenetriaminepentaacet ic acid. Our results suggest that this new and powerful class of contr ast agents have the potential for diverse and extensive application in MR imaging.