Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents

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Abstract
We have developed a new class of magnetic resonance imaging contrast agents with large proton relaxation enhancements and high molecular relaxivities. The reagents are built from the polyamidoamine form of Starburs™ dendrimers in which free amines have been conjugated to the chelator 2-(4-isothiocyanatobnenzyl)-6-methyl-diethylenetriaminepenta-acetic acid. The dendrimer gadolinium poly-chelates have enhancement factors, i.e., the ratlo of the relaxivity per Gd(III) ion to that of Gd(III)-diethylenetriaminepentaacetic acid, of up to 6. These factors are more than twice those observed for analogous metal-chelate conjugates formed with serum albumins, polylysine, or dextran. One of the dendrimer-metal chelate conjugates has 170 gadolinium ions bound, which greatly exceeds the number bound to other macromolecular agents reported In the literature, and has a molecular relaxivity of 5,800 (mM · s)−1, at 25 MHz, 20°C, and pH of 7.4. We observed that these dendrimer-based agents 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 have enhancement half lives of 40 ± 10 and 200 ± 100 min, much longer than the 24 ± 4 min measured for Gd(III)-diethylenetriaminepentaacetic acid. Our results suggest that this new and powerful class of contrast agents have the potential for diverse and extensive application in MR imaging.